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Micro-ultrasound (microUS) represents a potential alternative to multiparametric magnetic resonance (mpMRI) in guiding prostate biopsy, with level 1 evidence demonstrating non-inferiority to detect Grade Group ≥2 (GG ≥ 2) prostate cancer in biopsy-naïve men. However, a critical gap remains in the screening pathway, in which imaging is needed to identify men at risk and determine whether biopsy is warranted.

MUSIC-Screen is a phase 3, open-label, noninferiority 1:1 randomized controlled trial evaluating microUS as an alternative imaging compared to mpMRI for determining the need for prostate biopsy in biopsy- and imaging- naïve men at risk for GG ≥ 2. A total of 1284 men will be randomized to undergo either microUS or mpMRI. Men with PRI-MUS 3-5 or PI-RADS 3-5 lesion will undergo targeted and systematic biopsy. Men with negative imaging and PSA density ≥ 0.15 will undergo systematic biopsy, while those with PSA density < 0.15 will defer biopsy.

The primary outcome is GG ≥ 2 detection in each study arm. The primary hypothesis is that microUS is non-inferior to mpMRI for screening and detection of GG ≥ 2. Secondary objectives include comparison of GG ≥ 2 detection rates in targeted cores among patients with PRI-MUS or PI-RADS scores of 3-5, proportion of men who defer biopsy but are diagnosed with GG ≥ 2 within 8 years, assessment of the negative predictive value of each imaging modality, and health economic analyses.

MUSIC-Screen will determine whether microUS can be used as an imaging modality to inform biopsy decision making that is non-inferior to mpMRI for GG ≥ 2 prostate cancer detection. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06626022.

This prospective, single-center, randomized clinical trial (NCT05137561) enrolled biopsy-naïve men age 50-90 y with elevated levels of prostate-specific antigen (≥4 ng/mL) and abnormal digital rectal examination findings. All participants underwent mpMRI, and those with a PI-RADS score of 4 or greater were randomized into 2 arms. In arm 1, participants underwent PGPB for a [68Ga]Ga-PSMA-avid lesion, and participants in arm 2 underwent MCFB. Participants in arm 1 with PET-negative findings subsequently underwent MCFB, and participants with negative biopsy results underwent PET and PGPB. The primary outcome was the detection of PCa. Secondary outcomes included complication rates and participant-reported pain.

Of the 267 participants enrolled, 81.3% (217) had lesions with a PI-RADS score of 4 or greater and were randomized to either PGPB (n = 112) or MCFB (n = 105). PCa was detected in 97.1% of participants (101/104) in arm 1 and 81.0% (85/105) in arm 2 (P < 0.05). PGPB showed higher diagnostic accuracy for PI-RADS 5 lesions (100% vs. 95.1%, P = 0.09). Major complications were observed in arm 2 only (n = 5). Arm 1 had significantly fewer complications (10.8% vs. 51.4%, P < 0.01), a lower median visual analog scale score for pain (3 vs. 5), and shorter procedure times. The core positivity rate was higher in arm 1 (60% ± 20%), despite obtaining fewer cores.

[68Ga]Ga-PSMA-11 PGPB demonstrated higher diagnostic performance, fewer complications, and better tolerability compared with MCFB. This approach enables integrated diagnosis and staging, offering a promising alternative for efficient, safe, and accurate evaluation of prostate cancer.

To evaluate the feasibility and clinical value of a prostate cancer screening model incorporating total prostate-specific antigen (tPSA) and biparametric magnetic resonance imaging (bpMRI) in a Chinese population.

Between May 2024 and May 2025, 2 251 men aged 50 years or older from three community health service centers in Beijing were enrolled, who were randomly assigned to the precise screening group and the standard screening group in a 2 ∶ 1 ratio in the community health service centers. In the precision screening group, participants with tPSA≥4 μg/L underwent bpMRI; those with a prostate imaging reporting and data system (PI-RADS) score≥3 were recommended to undergo systematic combined with targeted biopsy, while those with tPSA≥10 μg/L and PI-RADS < 3 were recommended to undergo systematic biopsy alone. In the standard screening group, participants with tPSA≥4 μg/L were recommended to undergo systematic biopsy. The number of participants who actually underwent biopsy, biopsy positivity rate, and Gleason score concordance rate was recorded. The primary outcome measure was the detection rate of clinically significant prostate cancer (csPCa), and the intergroup comparisons were performed using the Mann-Whitney U test.

A total of 2 251 men were included in the analysis, with a median age of 68 years (range: 57-90 years). In the precision screening group (n=985), 115 (11.7%) participants had tPSA≥4 μg/L, of whom 30 underwent bpMRI. The recommended biopsy rate was 2.9% (29/985), and 20 participants actually underwent prostate biopsy. A total of 15 prostate cancer cases were detected, including 14 csPCa and one clinically insignificant prostate cancer. In the standard screening group (n=1 266), 111 (8.8%) participants had tPSA ≥4 μg/L, with a recommended biopsy rate of 8.8% (111/1 266); 26 of them underwent systematic biopsy, and 14 prostate cancer cases were detected, including 7 csPCa and 7 clinically insignificant prostate cancer. The overall positive biopsy rate in the precision screening group was 75.0%, which was not statistically significant compared with that in the standard screening group (58.3%, P=0.141). However, the csPCa detection rate in the precision screening group reached 70.0%, which was significantly higher than that in the standard screening group (26.9%), and the difference was statistically significant (P=0.004). Among the 29 diagnosed prostate cancer patients, 17 (58.6%) had localized disease, 10 (34.5%) had locally advanced disease, and 2 (6.9%) had metastatic disease. Among the 21 patients who underwent radical surgery, the concordance rate between biopsy and post-operative pathological Gleason scores was 70.0% in the precision screening group, higher than that in the standard screening group (36.4%), although the difference was not statistically significant (P=0.198).

The prostate cancer screening model based on serum tPSA combined with bpMRI demonstrates good feasibility, reduces unnecessary biopsies, optimizes the allocation of screening resources, and provides a basis for precision screening strategies. 目的: 探讨总前列腺特异性抗原(total prostate-specific antigen, tPSA)联合双参数磁共振成像(biparametric magnetic resonance imaging, bpMRI)的前列腺癌筛查模式在中国人群中的可行性与临床价值。 方法: 纳入北京市3家社区卫生服务中心2024年5月至2025年5月50岁及以上男性作为研究对象，按2 ∶ 1比例随机分为精准筛查组与标准筛查组。精准筛查组：tPSA≥4 μg/L者进行bpMRI检查；若前列腺影像报告和数据系统(prostate imaging reporting and data system, PI-RADS)评分≥3分，建议行系统+靶向穿刺；若tPSA≥10 μg/L且PI-RADS < 3分，建议行系统穿刺。标准筛查组：tPSA≥4 μg/L者建议行系统穿刺。记录两组实际接受穿刺人数，穿刺阳性率和Gleason评分一致率。主要结局指标为临床有意义前列腺癌(clinically significant prostate cancer, csPCa)检出率，组间比较采用卡方检验。 结果: 共2 251名男性纳入分析，中位年龄68岁(57~90岁)。精准筛查组985例，115例(11.7%)受试者tPSA≥4 μg/L，其中30例接受了bpMRI检查，建议穿刺率为2.9%(29/985)，实际接受前列腺穿刺者20例，最终检出前列腺癌15例，包括14例临床有意义前列腺癌(csPCa)和1例临床无意义前列腺癌。标准筛查组1 266例，111例患者tPSA≥4 μg/L，建议穿刺率为8.8%，其中26例接受系统穿刺，共检出14例前列腺癌，包括7例csPCa和7例临床无意义前列腺癌。精准筛查组的总体穿刺阳性率为75.0%，与标准筛查组(58.3%)相比，差异无统计学意义(P=0.141)；而精准筛查组csPCa穿刺阳性率(70.0%)显著高于标准筛查组(26.9%)，差异有统计学意义(P=0.004)。确诊的29例前列腺癌患者中，局灶期17例(58.6%)、局部进展期10例(34.5%)、转移性2例(6.9%)。在接受根治手术的21例患者中，精准筛查组穿刺标本与术后病理Gleason评分一致率为70.0%，高于标准筛查组(36.4%)，但差异无统计学意义(P=0.198)。 结论: 基于血清tPSA联合bpMRI的前列腺癌筛查模式具有可行性，可减少不必要的穿刺，优化筛查资源配置，可为精准筛查提供依据。

To evaluate prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) kinetics following PSMA-positron emission tomography (PET) and magnetic resonance (MR) guided stereotactic body radiation therapy (SBRT) and short-term androgen deprivation therapy with dominant intraprostatic lesion (DIL) boost in localized prostate cancer. METHODS AND MATERIALS: This prespecified analysis from the phase 2 PROBE trial (IRB approval: IEC 900917) included patients with intermediate- or high-risk prostate cancer treated with 5-fraction SBRT (36.25 Gy to prostate; 40 to 42.5 Gy to PSMA/MRI-defined DIL) and 6 months of androgen deprivation therapy. PSA kinetics relied on 3-monthly PSA levels. Longitudinal metabolic response, based on the adapted PET Response Criteria in Solid Tumors, was assessed using 68Ga-PSMA-PET/computed tomography done at SBRT completion, 3 to 6 months, and 9 to 12 months after SBRT completion. Cumulative genitourinary/gastrointestinal toxicities were reported per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.

Thirty enrolled patients (54% intermediate risk, 46% high risk) were included. A PSA <0.1 ng/mL was achieved in 79% of patients at 6 months and 50% at 12 months. The mean maximum standardized uptake value (SUVmax) decreased from 12.2 (range, 4.0-39.6) pretreatment to 3.2 at 3 to 6 months and 1.8 at 9 to 12 months. Complete response (CR) rates increased from 17% at SBRT completion to 48% at 3 to 6 months and 65% at 9 to 12 months. Patients achieving CR at 3 to 6 months reached a lower mean PSA (0.04 vs 0.3 ng/mL, P = .009). Those with PSA <0.1 ng/mL at 6 months were more likely to attain CR at 12 months (76% vs 28%, P = .003). An early standardized uptake value (SUV) "flare" was observed in 4 (14%) patients, resolving by 9 to 12 months. No National Cancer Institute Common Terminology Criteria for Adverse Events grade ≥3 genitourinary/gastrointestinal toxicity was seen.

PSMA-PET and MR guided prostate SBRT with DIL boost achieved deep PSA nadirs, gradual PSMA kinetics, and a favorable safety profile. About 80% of patients achieved a PSA <0.1 ng/mL at 6 months, with two-thirds achieving CR by 12 months post-SBRT. Achieving a PSA <0.1 ng/mL could potentially predict PSMA-CR. Early PSMA-CR at 3 to 6 months may predict durable PSA response and warrants further evaluation as a biomarker for risk-adapted strategies in localized prostate cancer.

Non-contrast MRI (bi-parametric MRI-bpMRI) has been investigated as a potential tool to be integrated in clinically significant prostate cancer (csPCa) screening. Moreover, artificial intelligence (AI) is emerging too as a potential support, especially for less-experienced radiologists. Therefore, the aim of this study was to evaluate the effectiveness of an AI-based software in csPCa screening using bpMRI, with a focus on supporting less-experienced radiologists.

A retrospective analysis was conducted within the PROSA-trial, a randomized, single-center study involving 759 men eligible for PCa screening. BpMRI were acquired using prostate imaging reporting and data system (PI-RADS) v2.1-compliant protocols and evaluated independently by an expert radiologist, a less-experienced reader, AI-based software, and the less-experienced reader with AI support. Diagnostic performance was assessed using ROC curves and inter-reader agreement (Cohen's kappa), using expert interpretation as the reference standard.

Four hundred ninety-nine bpMRI were analyzed. The AI-assisted less-experienced reader achieved the highest diagnostic performance (sensitivity 76.5%, specificity 97.2%, accuracy 95.8%, AUC 0.969), surpassing both AI-alone (sensitivity 58.8%, specificity 96.6%, accuracy 94.0%, AUC 0.952) and unaided less-experienced reader (sensitivity 67.6%, specificity 95.1%, accuracy 93.2%, AUC 0.932). Inter-reader agreement improved with AI assistance (from κ = 0.64 to 0.84). AI assistance reduced equivocal PI-RADS 3 cases (from 77 to 53) and improved exact agreement with the expert from 32.5% to 54.5%, while also reducing diagnostic discordance.

AI can support less experienced radiologists and enhance consistency in bpMRI interpretation, especially considering equivocal cases. Moreover, integrating AI into radiology workflows can alleviate reporting burden and help prioritize suspicious cases, offering critical advantages in high-volume PCa screening settings. KEY POINTS: Question Can AI improve the diagnostic performance and consistency of less experienced radiologists interpreting non-contrast prostate MRI in a screening setting? Findings AI assistance significantly improved effectiveness and inter-reader agreement in prostate MRI interpretation, particularly for less experienced radiologists within a screening population. Clinical relevance Integrating AI into prostate MRI workflows may enhance screening efficiency, reduce variability, and support equitable early detection of csPCa, with a positive impact on prioritization of reporting.

MRI is recommended for men with clinical suspicion of significant prostate cancer. Those with high clinical risk but non-suspicious or equivocal MRI often undergo prostate biopsy, but have a low likelihood of clinically significant prostate cancer, and a high incidence of clinically insignificant prostate cancer. We aimed to investigate whether gallium-68 ([68Ga]Ga)-prostate-specific membrane antigen (PSMA)-11 PET-CT could reduce the number of people requiring prostate biopsy and limit biopsy to targeted cores, without compromising clinically significant prostate cancer diagnosis.

In this multicentre, non-inferiority, phase 3, randomised controlled trial, done at at seven Australian hospitals, we recruited biopsy-naive participants with clinical suspicion of significant prostate cancer, equivocal (Prostate Imaging-Reporting and Data System [PI-RADS] 3) or non-suspicious (PI-RADS 2) MRI but high clinical risk (eg, prostate-specific antigen [PSA] density of >0·1 ng/mL/mL, strong family history of prostate cancer, abnormal digital rectal examination, BRCA mutation, PSA >10 ng/mL, PSA doubling time <36 months, or PSA velocity >0·75 ng/mL per year), PSA of 20 ng/mL or less, and clinical T2 disease or less. Participants were randomly assigned (1:1) using a centralised web-based system to undergo [68Ga]Ga-PSMA-11 PET-CT (experimental group) or systematic transperineal prostate biopsy (control group), using block sizes of two or four and stratification by study site. There was no masking for participants or investigators. Participants with positive [68Ga]Ga-PSMA-11 PET-CT (PRIMARY score 3-5) underwent PSMA-PET-targeted transperineal prostate biopsies, whereas those with a negative result (PRIMARY score 1-2) avoided biopsy. The co-primary outcomes were the proportion of participants with clinically significant prostate cancer, defined as a Gleason score of 3 + 4 (≥10% pattern 4) or higher, and the proportion of participants in the [68Ga]Ga-PSMA-11 PET-CT group who avoided biopsy within 6 months of random assignment. A two-sided 95% Wald CI based on a binomial model was used to estimate the risk difference in the proportion of participants with clinically significant prostate cancer (non-inferiority margin 10%) and to estimate the proportion of participants in the experimental group who had avoided biopsy 6 months after random assignment (20% threshold), analysed based on intention to treat. This trial is registered with ClinicalTrials.gov, NCT05154162, and participant follow-up is ongoing.

Between March 2, 2022, and Aug 24, 2025, 660 eligible male participants were enrolled and had a median age of 61 years (IQR 56-66), a median PSA of 5·2 ng/mL (4·0-7·0), and a median PSA density of 0·13 ng/mL/mL (0·09-0·17). There were PI-RADS 2 in 335 (51%) participants and PI-RADS 3 in 325 (49%) participants. Ethnicity data were not collected. 329 (50%) were assigned to the control group with systematic transperineal prostate biopsy, and 331 (50%) were assigned to the experimental group with [68Ga]Ga-PSMA-11 PET-CT. The proportion of participants with clinically significant prostate cancer in the experimental group (39 [12%] of 331) was non-inferior to the control (51 [16%] of 329; difference -3·7% [95% CI -8·9 to 1·5%]; p=0·0093). Use of [68Ga]Ga-PSMA-11 PET-CT avoided biopsy in 163 (49%) of 331 participants (95% CI 44 to 55%; p <0·0001). After prostate biopsy, participants reported similar proportions of pain (33 [21%] in the experimental group vs 62 [21%] in the control group), haematuria (60 [38%] vs 126 [43%]), and haematospermia (77 [48%] vs 133 [45%]).

[68Ga]Ga-PSMA-11 PET-CT could have the potential to improve the diagnostic pathway of patients with a high clinical risk but non-suspicious or equivocal prostate MRI. Further research, including health-economic analyses and validation with other PSMA radiopharmaceuticals, are needed to confirm the clinical implementation and generalisability of this approach. FUNDING: Prostate Cancer Foundation, National Health and Medical Research Council, St Vincent's Curran Foundation, and Peter MacCallum Cancer Foundation.

Index lesion-focused ipsilateral systematic biopsy (iSB) has been proposed as a core-reduction alternative to MRI-targeted biopsy combined with systematic biopsy (TB + SB) for prostate cancer, but prospective multicenter validation is limited.

This prospective multicenter trial (NCT06584279) enrolled biopsy-naive men with Prostate Imaging Reporting and Data System (PI-RADS) ≥4 lesions or PI-RADS 3 plus prostate-specific antigen (PSA) density ≥0.15 ng/mL/cm3. All underwent MRI-targeted biopsy (≥2 cores/lesion) with 12-core SB. Through core-level reclassification, the authors simulated TB + iSB (targeted biopsy combined with index lesion-ipsilateral systematic biopsy). The primary outcome was cancer detection rate (CDR) of clinically significant prostate cancer (csPCa; Grade Group ≥2) with a noninferiority margin of -3%. Secondary outcomes included clinically insignificant prostate cancer (cisPCa; Grade Group 1) detection and pathological concordance after radical prostatectomy.

Among 564 men (median age, 69 years; median PSA, 7.3 ng/mL), TB + iSB demonstrated a noninferior csPCa CDR versus TB + SB (40.78% vs. 42.38%; difference, -1.6 percentage points; 95% CI, -2.69 to -0.50), with the lower bound above the -3% noninferiority margin. The cisPCa CDR was slightly lower with TB + iSB than with TB + SB (13.83% vs. 14.36%; difference, -0.53 percentage points; 95% CI, -2.01 to 0.92). Among 189 surgical patients, pathological concordance was similar, whereas upgrading was numerically more frequent and downgrading numerically less frequent under simulated TB + iSB.

TB + iSB met the prespecified noninferiority criterion for csPCa detection relative to TB + SB and may represent a promising core-reduction strategy in transperineal MRI-guided biopsy, although the full protocol still provided additional contralateral information.

PSMA-PET offers an opportunity to reduce the mischaracterization of disease in active surveillance (AS) and focal therapy (FT) candidates. We describe the results of a pilot clinical trial evaluating 18F-radiohybrid(rh)PSMA-7.3-PET/MRI to detect occult adverse pathology among potential AS and FT candidates (NCT05852041).

We enrolled 20 men with low risk or favorable intermediate risk prostate cancer and Decipher score ≥ 0.45 diagnosed after an MRI-informed prostate biopsy. All patients underwent PSMA-PET/MRI followed by either PET/MRI-guided biopsy or radical prostatectomy within 90 days. The outcome of interest was detection of grade group (GG) 3-5 disease, seminal vesicle invasion (pT3b), or lymph node involvement (pN1). A detection rate of 15% for this outcome was considered clinically significant. Management decisions and confidence in those decisions were recorded before and after the scan using a 3-point scale. A paired t-test was performed to compare the change in confidence decisions.

At enrollment, 17 patients (85%) had favorable intermediate risk and 3 (15%) had low risk prostate cancer. The median Decipher score was 0.58 (IQR 0.49-0.65). Five patients (25%) demonstrated the outcome of interest based on upgrading alone. None had upstaging to pT3b or pN1. Major changes in management plan occurred in 7 patients (35%). Average confidence in decisions improved from moderate (2.05) to high (2.80) after the scan (p < 0.001).

18F-rhPSMA-7.3-PET/MRI can detect occult higher risk disease in men who are otherwise candidates for AS or FT. The scan prompted major changes in management and increased confidence in the final treatment strategy.

Non-White patients are poorly represented in prostate cancer trials. MRI PI-RADS scoring was developed in primarily White populations, but prostate cancer differs in non-White men. We aimed to explore differences in PI-RADS calibration for Asian and Black men.

This is a secondary analysis of PREVENT, a multi-institutional study of infection rates for transrectal vs. transperineal biopsy. We compared cancer detection for self-identifying Asian and Black men. We compared detection rates on a per-person basis, stratified by index PI-RADS lesion, to White men, using Fisher's exact and logistic regression.

Of 665/752 trial patients with PI-RADS 3-5 lesions, 88 (13%) were Black and 36 (6%) were Asian. Black men were younger at diagnosis with increased rates of overall (70% vs. 43%%, P = 0.004) and clinically significant prostate cancer (60% vs. 27%, P = 0.003) and Asian men had decreased rates of overall (0% vs. 47%, P = 0.004) and clinically significant prostate cancer (0% vs. 27%, P = 0.003) in PI-RADS 3 lesions compared to White men. On multivariable regression, Black men with PI-RADS 3/4 lesions had higher odds of overall (OR 1.17, P = 0.009) and clinically significant prostate cancer (OR 1.20, P = 0.004) and Asian men had lower odds of overall (OR 0.79, P = 0.01) but not clinically significant prostate cancer (OR 0.94, P = 0.5).

Black men with PI-RADS 3/4 lesions had 20% higher odds of clinically significant prostate cancer than White men while all PI-RADS 3 lesions in Asian men were negative. These findings suggest PI-RADS may require differential interpretation when assessing prostate cancer risk in non-White men. TRIAL REGISTRATION: Registered at ClinicalTrials.gov ( NCT04843566 , https://clinicaltrials.gov/study/NCT04843566 ).

To determine which treatment parameters optimize focal therapy for intermediate-risk prostate cancer by balancing oncologic control with healthy tissue preservation, in a phase 2b multicenter trial of MRI-guided Focused Ultrasound (MRgFUS). Additionally, to assess the relationship of ablation volume relative to lesion volume with oncologic outcomes, urinary, and erectile function.

In this retrospective interpretation of prospectively acquired data, the non-perfused volume (NPV) of prostate tissue encompassing the MRI-visible lesion volume defined the ablation-volume-to-lesion-volume ratio (ALVR). Oncologic efficacy was assessed as the absence of clinically significant (GGG ≥ 2) cancer in the treatment zone at 24-month biopsy. Associations between ALVR and outcomes were assessed using Student's t-tests. Baseline characteristics were compared using Kruskal-Wallis tests.

Eighty-nine men (mean age, 63 years ± 7) had MRI-visible lesions with a volume of 0.47 mL (IQR: 0.20-0.95), with a surrounding NPV of 6.9 mL (IQR: 5.2-10.4). Men achieving oncologic efficacy had twice the ALVR compared to those with recurrence at the treatment site (17 vs 8, mean difference 8.8, 95% CI: 2.1, 16, p = 0.013). Increasing NPV relative to total prostate volume did not improve oncologic outcomes. Baseline characteristics did not significantly differ between men with and without GGG ≥ 2 at 24-month biopsy. ALVR did not differ in men with new erectile dysfunction (mean difference in ALVR: 2.1, 95% CI: -12, 16, p = 0.8) or urinary symptoms (mean difference in ALVR 4.0, 95% CI: -21, 29, p = 0.71).

In patients with intermediate-risk prostate cancer, higher ALVR was associated with superior 2-year oncologic outcomes without increased risk of urinary or erectile dysfunction. KEY POINTS: Question What treatment parameters optimize focal therapy for prostate cancer by balancing healthy tissue preservation with favorable oncologic outcomes? Findings Patients without residual cancer at 24-month biopsy had twice the ALVR of those with recurrence, with no adverse impact on erectile or urinary function. Clinical relevance While fixed intra-prostatic margins (e.g., 5 mm or 10 mm) are commonly prescribed in focal therapy, this study highlights the importance of scaling the ALVR in the treatment plan to achieve sufficient oncologic coverage.

To assess the oncological outcomes of targeted microwave ablation (TMA) using organ-based tracking (OBT) Fusion® via KOELIS Trinity® (KOELIS, Meylan, France) in men with intermediate-risk prostate cancer (PCa): the VIOLETTE trial (ClinicalTrials.gov identifier: NCT04582656) PATIENTS AND

In this prospective phase II, multicentre European study, men with a prostate-specific antigen (PSA) level <20 ng/mL, a single magnetic resonance imaging (MRI)-visible lesion ≤15 mm, International Society of Urological Pathology (ISUP) Grade Group 2 on MRI-targeted biopsy, and clinical T stage ≤2, were enrolled. The microwave applicator was placed using OBT Fusion guidance, either transperineally or transrectally. The primary endpoint was the absence of clinically significant PCa (csPCa), defined as ISUP Grade Group ≥2, within the treated area at 12 months. Secondary endpoints included safety, functional outcomes using validated measures, and the need for subsequent radical treatment.

A total of 76 patients were treated across six centres with 66 (87%) completing the 12-month follow-up. At 6 months, six patients had csPCa after positive MRI control, including four within the treated area. At 12 months, csPCa was detected in 15 additional patients, including nine in-field recurrences, yielding an 81% in-field csPCa-free rate. Five serious adverse events in three patients were reported. Sexual (-2.5 points; P < 0.001) and ejaculatory (-1 points; P < 0.001) scores decreased significantly, whereas urinary function remained stable. Radical treatment was required in four (5.2%) patients at 12 months.

Targeted microwave ablation using OBT Fusion technology appears to be a safe and effective focal therapy procedure for localised intermediate-risk PCa. The VIOLETTE trial achieved its primary endpoint, with 81% patients free of in-field csPCa at 12 months.

The MIRAGE (Magnetic resonance imaging-guided versus computed tomography-guided stereotactic body radiotherapy for prostate cancer) trial (NCT04384770) showed that aggressive planning target volume (PTV) margin reduction, achieved by leveraging the advanced image-guidance of magnetic resonance imaging guided radiation therapy, led to lower toxicity after stereotactic body radiation therapy (SBRT) to the prostate compared with computed tomography guided SBRT (CTgSBRT) with a standard PTV margin. It is unknown whether the dosimetric benefit of reducing PTV margins alone-independent of the other components of advanced image guided radiation therapy that allowed margin reduction-would be predicted to replicate this decrease in toxicity. METHODS AND MATERIALS: We retrospectively replanned 16 CTgSBRT patients with 3- and 2-mm PTV margins from the 4 mm used in MIRAGE to compare with magnetic resonance imaging guided SBRT (MRgSBRT) patients' radiation therapy plans (n = 79), which used a 2-mm PTV margin. We compared target and organs-at-risk dosimetry and performed multivariable linear regression to control for potentially related covariates. We estimated normal tissue complication probability to assess the potential impact of PTV margin reduction on the risks of rectal and bladder toxicity.

Compared with MRgSBRT patients, replanned CTgSBRT patients had similar (3 mm) or statistically significantly improved (2 mm) rectal dosimetry and similar bladder dosimetry (2 mm). These trends persisted on multivariable linear regression. Normal tissue complication probability modeling demonstrated a statistically significant improvement in rectal toxicity whereby margin reduction from 4→3 mm and 4→2 mm resulted in relative reductions in toxicity probabilities of 56% and 78%, respectively. For bladder toxicity, reducing margins from 4 to 3 or 2 mm reduced the probability of bladder toxicity by 96%, although these relative differences were not statistically significantly.

Reducing PTV margins for CTgSBRT plans produced similar to improved organs-at-risk dosimetry compared with the clinical MRgSBRT plans, which in turn would be predicted to reduce toxicity when compared to larger margin CTgSBRT plans. This improvement in dosimetry could explain the reduction in modeled rectal toxicity, but the impact on bladder toxicity is unclear, with large, but nonsignificant relative differences underscoring our incomplete understanding of the drivers of post-SBRT urinary toxicity.

The goal of this study was to curate a prostate MRI dataset from a screening population and to train and evaluate a deep-learning segmentation method on the same data.

An artificial intelligence (AI) system, based on a deep-learning-based segmentation model (nnU-Net method), was trained and evaluated with MRI data from a prostate cancer screening population (G2-trial). The goal of the AI was to detect clinically significant prostate cancer (csPC), defined as International Society of Urological Pathology (ISUP) grade 2 or higher. The AI system was compared to the performance of radiologists using PI-RADS v2 evaluation metrics. Histopathology was used as the reference standard in the dataset. To better verify negative cases, 288 men were subject to systematic biopsies regardless of MRI findings, and all men had at least 3 years of follow-up.

A total of 1354 MRI examinations in 1254 men with a median age of 58 years (range 50-63 years) were randomly divided into a training set (1086 examinations) and a test set (268 examinations). The resulting area under the receiver operating characteristic curve (AUROC) was 0.83 (95% CI 0.73-0.92) for the AI system; however, with significantly lower specificity at matched sensitivity levels compared to radiologists.

A prostate MRI dataset from a screening population with histological confirmation was curated and evaluated with AI. The neural network trained and tested on this data produced lower specificities than the radiologists. KEY POINTS: Question Does an AI system trained in a screening cohort perform as well as radiologists? Findings An AI trained on screening data achieved an AUROC of 0.83 (95% CI 0.73-0.92) with lower specificity at the same sensitivity levels as radiologists. Clinical relevance An AI system trained in a screening population has lower specificity than radiologists using PI-RADS v2.

To assess the safety of using combined Gallium68-prostate-specific membrane antigen (PSMA)-positron emission tomography (PET)/computed tomography (CT) (68Ga-PSMA-PET/CT) and multiparametric magnetic resonance imaging (mpMRI) for planning dominant intraprostatic lesion (DIL) boost in prostate stereotactic radiation therapy (SBRT) for dose escalation (PROBE). METHODS AND MATERIALS: Patients with intermediate- or high-risk prostate adenocarcinoma with DIL identified on mpMRI and 68Ga-PSMA-PET/CT and suitable for SBRT were enrolled in this phase 2 trial. 68Ga-PSMA-PET/CT was fused with mpMRI for gross tumor volume (GTV) delineation. Semiautomatic contouring of DIL was performed using 20% to 90% of the maximum standardized uptake value (SUVmax) (DILx%). Concordance metrics were used to select the DILx% matching closest to GTVMRI (GTVPET). Prostate (36.25 Gy), pelvic nodes (25 Gy), GTVunion: GTVPET ∪ GTVMRI (40 Gy), and GTVoverlap: GTVPET ∩ GTVMRI (42.5 Gy) were planned for 5-fraction SBRT. All patients received androgen deprivation therapy (ADT) for 6 months. The primary endpoint for the present analysis was concordance (volumetric and spatial) between GTVMRI and GTVPET. Secondary endpoints included the percentage SUVmax threshold for GTVPET contouring (%SUVGTV-PET) and cumulative acute (≤90 days) urinary and gastrointestinal toxicity using Common Terminology Criteria for Adverse Event (CTCAE) v5.0.

Thirty patients (54% intermediate risk, 46% high risk) were enrolled. GTVMRI and GTVPET showed strong volumetric correlation (Spearman correlation coefficient ρ = 0.817, 95% CI, 0.64-0.91; P < .001). The median Dice similarity coefficient, Jaccard index, and the mean Hausdorff distance for PET and magnetic resonance imaging boost volumes were 0.56, 0.37, and 2.2, respectively. The median %SUVGTV-PET was 48% (IQR, 40%-58%). There was an inverse correlation between DIL SUVmax and %SUVGTV-PET (Spearman correlation coefficient ρ = -0.598, 95% CI lower -0.79, upper -0.29; P < 0.001). Cumulative grade 2 acute urinary and GI toxicity were 13.3% and 6.6%, respectively, with no grade ≥3 toxicities.

Boost volumes on 68Ga-PSMA-PET/CT and mpMRI were volumetrically similar, however, with poor spatial concordance. The %SUVmax threshold for GTVPET contouring correlated inversely with DIL SUVmax and was a median of 48%. Based on the favorable acute toxicity profile, PSMA-PET-guided intraprostatic boost is likely to be safe for dose escalation in prostate SBRT.

Escalating dose to the gross tumor volume (GTV) while de-escalating dose to the prostate clinical target volume (CTV) and using a 0-mm planning target volume margin can potentially minimize toxicity without compromising biochemical control in patients with intermediate-risk prostate cancer. We evaluated the technical feasibility of this approach in online adaptive magnetic resonance imaging (MRI)-guided stereotactic body radiation therapy. METHODS AND MATERIALS: The DESTINATION-MRL trial ran as 3 parallel single-center phase 2 non-randomized trials in 3 different institutes. Each institute enrolled 20 patients who were all treated on a 1.5T Unity MR-linear accelerator (MR-Linac). The GTV was defined as tumor(s) visible on multiparametric MRI. The CTV was defined as the whole prostate. The proximal 1-2 cm of the seminal vesicles were included in the CTV at the clinician's discretion. An intraprostatic margin of 4 mm was applied to the GTV to account for delineation and pathological uncertainty (GTV 4 mm) and no planning target volume margin was applied to the CTV. All patients were treated with 30 Gy in 5 fractions to the CTV and an isotoxic boost of 45 Gy to the GTV 4 mm. The primary endpoint was technical feasibility, defined as an accumulated GTV D90% of >42 Gy on the post-treatment MRI in ≥90% of the patients.

Between May 2023 and September 2024, 60 patients were treated, of which 54 were included for analysis. An accumulated GTV D90% of >42 Gy was reached in 46 patients (85%). Analysis per institute showed that this criterion was reached in 10 of 14 patients (71%) in institute 1 and in 18 of 20 patients (90%) in both institutes 2 and 3.

Although toxicity-minimizing radiation therapy in online adaptive MRI-guided stereotactic body radiation therapy for prostate cancer was feasible in 2 of the 3 institutes, robust coverage of the GTV and CTV could not be assured in the absence of a gating strategy.

The combined targeted and systematic biopsy (CTSBx) was the standard scheme for patients with visible suspicious lesions on MRI in recent years. 2024 European Association of Urology guideline recommended targeted and perilesional biopsy (TPLBx) for the diagnosis of patients with MRI-visible suspicious lesions. This randomized controlled trial aims to comprehensively evaluate the efficacy and safety profiles of TPLBx and CTSBx schemes.

A single-center noninferiority randomized controlled trial consecutively enrolled 380 biopsy-naïve patients (CTSBx: n = 190, TPLBx: n = 190) with a single unilateral suspicious lesion on prostate MRI from June 2024 to November 2024. The noninferiority margin was -15%. All biopsies were undertaken transrectally through the cognitive fusion technique. The primary outcome was Grade Group (GG) ≥ 2 cancer (GG ≥ 2-PCa) detection rate.

The GG ≥ 2-PCa (58% vs 58%, risk difference [RD]: 0.53% [95% CI: -9.4% to 11%]) and GG ≥ 3-PCa (30% vs 30%, RD: 0.53% [95% CI: -8.7% to 9.7%]) detection rates of TPLBx were noninferior to that of CTSBx (P < .001). There was no significant difference in PCa and GG1-PCa detection rates between the 2 groups (P > .050). The complication rate of TPLBx was significantly lower than that of CTSBx group (Clavien-Dindo scale ≥ 1: 62% vs 74%, P = .023), especially for bleeding-related complications (rectal bleeding: 34% vs 48%, P = .003; hematuria, 39% vs 56%, P < .001) and rectal pain (25% vs 34%, P = .018). TPLBx could significantly shorten the procedure time and saved the pathological cost (P < .001).

For patients with a single unilateral suspicious lesion on prostate MRI, TPLBx achieved the noninferior diagnostic efficacy of clinically significant PCa and better safety than the CTSBx scheme. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06482658.

Metachronous oligometastases may represent a favorable disease state for local therapy after prior curative treatment. Stereotactic Magnetic Resonance-Guided Adaptive Radiation Therapy (SMART) provides precise targeting of nodal and soft tissue metastases. The primary objective was to assess the feasibility and safety of SMART for abdominopelvic metachronous oligometastases. Secondary objectives included assessing rates of toxicities and evaluating local control (LC). METHODS AND MATERIALS: Ten patients were enrolled with solid tumor metachronous abdominopelvic nodal or soft tissue metastases, ≤7 cm in maximal diameter, and ≤3 sites of active disease. All patients received 40 Gy in 5 fractions. Acute toxicities were graded per Common Terminology Criteria for Adverse Events v5 per-protocol follow-up over 1 year. Late toxicities and clinical outcomes were elucidated by chart review. LC, distant progression-free survival, and overall survival were analyzed using the Kaplan-Meier Method.

Eight patients with prostate cancer and 2 with renal cell carcinoma were enrolled in the study. All patients were successfully treated with SMART per-protocol without complications. The median follow-up after SMART was 4.22 years. Three patients experienced acute grade 1 toxicities; there were no higher grade or late toxicities. Among these 10 patients, 4-year LC and overall survival were both 90%, and 4-year distant progression-free survival was 20%. Two patients (1 prostate cancer, 1 renal cell carcinoma) remain with no evidence of disease, each at over 4 years following SMART and without receiving further systemic or local therapies.

With 4 years median follow-up, this small prospective trial reports low toxicity, supporting the feasibility of SMART metastasis-directed therapy for metachronous oligometastases with minimal risk of acute or late toxicity.

Three-dimensional (3D) augmented reality (AR) and artificial intelligence (AI) technologies have recently been introduced to enhance guidance during robot-assisted radical prostatectomy (RARP). By overlaying virtual and real-time images, this approach helps accurately localize hidden lesions during surgery, enabling the execution of tailored procedures. This study aimed to evaluate whether 3D-AI-AR guidance reduces positive surgical margins (PSMs) compared with standard tw0-dimensional (2D) magnetic resonance imaging (MRI)-based interventions.

In this prospective, multicenter randomized controlled trial (NCT06318559), 133 patients with extracapsular extension or bulging at preoperative MRI were enrolled and randomized (2:1) to either 2D MRI-guided (n = 84) or 3D-AI-AR-guided RARP (n = 49). All the patients underwent nerve-sparing RARP. Intraoperative selective biopsies were then performed at the level of the preserved neurovascular bundle (NVB): cognitive in the MRI group and AR guided in the 3D group. The primary outcomes included PSM rate. Prostate-specific antigen (PSA) levels, continence, and potency recovery were assessed during the 12 mo of follow-up. The use of postoperative radiotherapy was recorded. Biochemical recurrence (BCR) was defined as PSA >0.4 ng/ml. All the analyses were conducted with SAS Statistics Software v.9.4. KEY FINDINGS AND LIMITATIONS: Baseline and intraoperative characteristics were similar between the groups. While PSMs on prostate surface were comparable (p = 0.8), 3D-guided excisional biopsies had a significantly higher positivity rate (52% vs 13%; p = 0.001), allowing an improved margin control. The 3D group had a lower overall PSM rate (22% vs 39%; p = 0.047), required less postoperative RT (18% vs 35%; p = 0.046), and showed higher continence at 12 mo (91% vs 71%; p = 0.03). Potency and BCR rates were similar. CONCLUSIONS AND CLINICAL

The execution of a 3D-AI-AR-guided biopsy at the level of preserved NVBs during nerve-sparing RARP allows correct identification of the tumor with subsequent improvement of margin control. Longer follow-up is required to assess the functional and long-term oncological outcomes of this approach.

Prostate-specific antigen (PSA)-based screening for prostate cancer (PCa) has limited accuracy, and it is linked to overdiagnosis. The PROSA trial aimed to evaluate whether a contrast-free biparametric magnetic resonance imaging (bpMRI)-first screening strategy improves the detection of clinically significant PCa (csPCa) as the primary outcome. The secondary outcomes included overall PCa detection, benefit-harm metrics, and cost effectiveness from a health care payer perspective.

This single-center, randomized controlled trial enrolled 816 asymptomatic men aged 49-69 yr (≥40 yr with a PCa family history). Participants were randomized into two arms: arm A underwent bpMRI regardless of the PSA levels; arm B received bpMRI only if PSA ≥3 ng/ml (or 2.5 ng/ml with a family history). Men with Prostate Imaging Reporting and Data System score ≥3 were directed to a targeted biopsy. Imaging and pathology assessors were blinded; csPCa is defined as International Society of Urological Pathology grade group ≥2. The primary outcomes included csPCa detection, benefit-harm metrics, and cost effectiveness from a health care payer perspective. KEY FINDINGS AND LIMITATIONS: Among 759 randomized men, biopsy and csPCa detection rates were higher in arm A (10.8% and 4.6%, respectively) than in arm B (5.2% and 1.8%, respectively), with a relative risk of 2.6 (95% confidence interval 1.1-6.1; p = 0.05) for the csPCa detection rate. Benefit-harm metrics favored the MRI-first strategy, showing higher grade selectivity (1.89 vs 1.75), biopsy efficiency (0.74 vs 0.54), and biopsy avoidance (23.1 vs 11.9). No serious adverse event was recorded. The MRI-first strategy yielded an incremental cost-effectiveness ratio of €2201.75 per csPCa case detected. Limitations include single-round design and short follow-up. CONCLUSIONS AND CLINICAL

In this randomized screening trial, a contrast-free MRI-first pathway improved csPCa detection, enhanced benefit-harm metrics, and showed favorable cost effectiveness.

DOminant-TArgeted Boost in Localized Prostate Cancer (DOTA-2) is a phase II randomised controlled trial comparing two ultra-hypofractionated radiotherapy with dominant intraprostatic lesion (DIL) boost: 26 Gy/2F, 32 Gy to DIL vs 36.25 Gy/5F, 40 Gy to DIL, without androgen deprivation therapy (ADT), for prostate cancer.

Patients with low- to favourable-intermediate-risk prostate cancer were randomly assigned to receive either 2 fractions or 5 fractions. Magnetic resonance-guided adaptive radiotherapy (MRgART) was delivered using the Unity® MR-Linac with the adapt-to-shape workflow for every fraction. The primary endpoint was cumulative grade ≥2 acute genitourinary (GU) and gastrointestinal (GI) toxicity. Secondary endpoints included quality of life in the urinary and sexual domains. An interim analysis of acute GU and GI toxicities was conducted on the first 22 patients from the total planned cohort of 44.

Patients were randomly assigned to either the 2-fraction (N = 10) or 5-fraction stereotactic body radiotherapy (SBRT) (N = 12), stratified by risk group, prostate volume, and DIL location. The median follow-up time was 16 weeks. The cumulative worst acute grade ≥2 GU toxicity was reported in 2/10 (20%) patients in the 2-fraction group vs 4/12 (33.3%) in the 5-fraction group (P = 0.48), with no cases of grade ≥3 acute GU toxicity. No grade ≥2 acute GI toxicity was observed in either arm. The two groups had no significant difference in International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) scores.

Two-fraction SBRT with a DIL boost, delivered using MRgART without ADT, demonstrated acceptable acute GU and GI toxicity in this interim analysis, suggesting the feasibility of continuing the investigation.

Multi-parametric MRI (mpMRI) datasets often vary between sites due to differences in acquisition protocols.

Evaluate adherence of multi-site mpMRI dataset to minimum technical standards (MTS) of PI-RADSv2.1. STUDY TYPE: Prospective. SUBJECTS: Six hundred patients (Age (years): ≤ 49 = 0.8%, 50-59 = 10.7%, 60-69 = 47.0%, ≥ 70 = 41.5%) with intermediate-risk prostate cancer (PCa) imaged across 124 institutions prior to radiotherapy. FIELD STRENGTH/SEQUENCE: 3T, 1.5T, and 1.16T, T2-weighted (T2w): fast spin-echo, diffusion-weighted imaging (DWI): single-shot echo-planar imaging, and dynamic contrast-enhanced (DCE): T1-weighted 3D fast spoiled gradient echo. ASSESSMENT: Scanner vendors included Siemens, GE, Philips, Toshiba, and Hitachi. Degree of adherence to PIRADSv2.1 was determined as the proportion of datasets that met MTS. Mean and standard deviation of parameter values were calculated where applicable. Prostate imaging quality (PI-QUAL)v2 scores were assigned by one of three observers in 491 datasets. Evaluation of DICOM metadata consistency was performed. STATISTICAL TESTS: Fisher's exact test to assess changes in MTS adherence over time and by field strength; Harrel's C-index to compare MTS adherence to PI-QUAL score. A p value of < 0.001 is considered statistically significant after Bonferroni correction.

Eighty-two percent of MTS showed greater than 75% adherence. Low adherence was found in the in-plane dimension (frequency-encoding direction) for T2w images (57%, mean = 0.45 ± 0.16 mm) and field of view (FOV) for DW images (62%, mean = 22.67 ± 4.70 cm). Only 50% of datasets used the recommended high b value image to compute the apparent diffusion coefficient map. Adherence improved significantly over time for one T2w and two DWI parameters; the adherence of FOV improved significantly at 3T for T2w and DWI sequences. C-index values for two T2w and two DWI parameters demonstrated a relationship between PI-RADS MTS and PI-QUAL score. Ten percent of anonymized datasets were stripped of some sequence information. DATA

Results show promise for mpMRI standardization in characterization of PCa and identify key parameters that remain variable across datasets and institutions. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03367702. Variability in the way MRI scans are performed at different institutions and with different types of MRI scanners can make it difficult to obtain consistent results. We examined the MRI scan parameters of a large, multi‐institutional dataset to determine how well they follow the guidelines outlined in the Prostate Imaging‐Reporting Data System (PI‐RADS)v2.1. We found most of the parameters showed high adherence to PI‐RADSv2.1. Further examination of those parameters with lower adherence may provide insight that could be beneficial to future efforts to standardize the way in which MRI scans are performed.

Forty-two patients with biopsy-confirmed, high-risk PCa were enrolled in this single-center, prospective, phase 2 clinical trial between September 2020 and May 2023 at San Raffaele hospital. All patients underwent [68Ga]Ga-PSMA-11 PET/MRI with mpMRI, and 36 had additional imaging with [68Ga]Ga-RM2 PET/MRI. All patients were included in the patient-level T staging analysis. Twenty-five patients were treated with radical prostatectomy with extended lymphadenectomy and considered for N staging analysis. Sixteen patients underwent all imaging and surgical procedures needed for coregistration between imaging and histology and were included in the lesion-based analysis for T staging. Two expert nuclear medicine physicians reviewed [68Ga]Ga-PSMA-11 and [68Ga]Ga-RM2 PET images with knowledge of the patients' available clinical and imaging information. mpMRI was interpreted as the standard of care by 2 expert radiologists using Prostate Imaging Reporting and Data System, version 2, criteria. Peripheral whole-blood samples were collected at the time of patient's enrollment to assess their association with lymph node involvement on histology.

In the patient-based analysis, [68Ga]Ga-PSMA-11 PET and mpMRI identified at least 1 intraprostatic lesion in all patients, whereas [68Ga]Ga-RM2 PET results were negative in 3 of 36 patients. The lesion-level analysis performed in 16 patients showed that, in this cohort, the dominant intraprostatic lesion was always detected by [68Ga]Ga-RM2 PET, whereas both [68Ga]Ga-PSMA-11 PET and mpMRI missed it, reporting a false-positive finding elsewhere. For N staging analysis, [68Ga]Ga-PSMA-11 PET had the highest sensitivity among the investigated imaging modalities (sensitivity, 0.375). Blood analysis showed that a higher fraction of polymorphonuclear-myeloid-derived suppressor cells (MDSCs) over monocytic MDSCs was significantly associated patients with lymph node involvement on histology (P = 0.0285).

All imaging modalities showed high sensitivity for the preoperative detection of primary PCa, but only [68Ga]Ga-RM2 PET correctly identified the dominant lesion in all patients who underwent lesion-based subanalysis. The identification of lymph node involvement remains challenging, with [68Ga]Ga-PSMA-11 PET reaching a sensitivity of only 0.375. In this regard, the polymorphonuclear MDSC-to-monocytic MDSC ratio may represent a valuable biologic marker of lymph node involvement in patients with high-risk PCa and warrants further investigation.

The RAPID study was a randomized, controlled, single-center, open-label phase 3 trial comparing the diagnostic efficacy of 68Ga-PSMA-11 PET/MRI with systematic transrectal ultrasound-guided prostate biopsy. In total, 220 men with suspected PCa were randomized to either a standard (random 12-core biopsy; RB) group or an image-guided biopsy (IGB) group. Biopsy, prostatectomy histology, and follow-up visits served as references.

PET/MRI prospectively predicted 91 of 113 histologically verified tumors, corresponding to a sensitivity of 80.5% and a positive predictive value of 84.3%. Among tumors characterized as ISUP GG of 3 or greater (n = 60), PSMA PET/MRI prospectively detected 95% (n = 57). The IGB group demonstrated slightly higher sensitivity, specificity, positive predictive value, and negative predictive value compared with the RB group (79.3%, 94.7%, 85.2%, 92.2% vs. 74.2%, 88.0%, 71.9%, 89.2%). Seventy-nine patients were eligible for a direct IGB and RB subanalysis, with IGB detecting 15 additional cases. PET/MRI showed high specificity (94%) and negative prediction (86%) for tumor aggressiveness. In a median follow-up period of 3 y, an aggressive course of disease was detected in 25 of 199 patients. RB correlation identified 24 patients with an ISUP GG of 3 or greater with aggressive disease development during follow-up, compared with 23 patients identified by PET/MRI. Negative prediction of both methods was comparably high at 99%; however, PET/MRI overestimated fewer patients (21) as aggressive compared with RB (34).

PSMA-targeted PET/MRI-guided biopsy is a reliable, less invasive method for detecting and characterizing PCa in a cohort with moderately increased PSA values, potentially reducing unnecessary biopsies and provides a reliable prognosis of the course of disease. These results support the integration of modern imaging techniques into clinical practice to improve the treatment of PCa.

In a prospective, international study supported by the International Atomic Energy Agency, 775 patients with high-risk or unfavorable intermediate-risk PCa from 12 centers across 11 countries-including low-, middle-, and high-income settings, scheduled for radical prostatectomy based on conventional imaging (including bone scanning and pelvic MRI) underwent 68Ga-PSMA-11 PET/CT before treatment. PET and MRI findings were compared with radical prostatectomy histopathology, and the impact of PET on radical prostatectomy was assessed.

68Ga-PSMA-11 PET/CT detected metastatic disease (M1) in 20.4% of cases, altering management and preventing prostatectomy in 24.0%. The accuracy for seminal vesicle invasion was 90.1% for 68Ga-PSMA-11 PET/CT versus 57.3% for MRI, and for lymph node metastases it was 91.1% for 68Ga-PSMA-11 PET/CT versus 69.7% for MRI. In 13.1% of patients (78/593), there were discordant results between 68Ga-PSMA-11 PET/CT and histopathology. 68Ga-PSMA-11 PET/CT had false-negative lymph node findings in 8.6% of cases, with the most clinically significant being 4.5% of patients incorrectly staged as N0. False-positive lymph node findings at 68Ga-PSMA-11 PET/CT occurred in 4.5% of patients.

68Ga-PSMA-11 PET/CT significantly improves staging accuracy, reducing the indication for prostatectomy and impacting treatment decisions. These findings, from a broad international cohort including low-, middle-, and high-income countries, support the global adoption of 68Ga-PSMA-11 PET/CT into standard staging protocols for high-risk PCa.

Previous studies have indicated that regional saturation prostate biopsy (RSB) is more effective than targeted biopsy (TB) or systematic biopsy (SB) for patients with prostate-specific antigen (PSA) levels between 4 and 20 ng/mL. However, its efficacy in patients with PSA levels ≥ 20 ng/mL remains unclear. PATIENTS AND

In this prospective, single-center, randomized controlled trial, we enrolled patients with PSA levels greater than 20 ng/mL and suspicious magnetic resonance imaging (MRI) findings from January 2021 to August 2023. The participants were randomized to undergo RSB or TB, and SB was also performed. The primary endpoint was the detection rate of clinically significant prostate cancer (csPCa), defined as an International Society of Urological Pathology (ISUP) grade ≥ 2.

RSB detected csPCa more frequently than did TB (90.2% versus 82.9%, p = 0.01) and SB (90.2% versus 82.5%, p = 0.01). Supplementary SB did not increase csPCa detection in the RSB group but did increase it in the TB group. Subgroup analysis revealed that RSB was particularly effective for patients with PSA levels between 20 and 50 ng/mL, prostate imaging-reporting and data system (PI-RADS) score of 3 lesions, prostate volume (PV) > 45 mL, and PSA density (PSAD) < 1.0 ng/mL/cc. However, the single-center design limits the generalizability of our findings.

Our trial suggests that RSB is superior to TB in detecting significant prostate cancers among patients with high PSA levels (≥ 20 ng/mL). Notably, perilesional biopsy is crucial for those with PSA levels between 20 and 50 ng/mL, larger PV, low PSAD, and low PI-RADS scores, enhancing csPCa detection.

Whether the performance in detecting local recurrent lesions is similar between multiparametric MRI (mpMRI) and PSMA PET/CT at biochemical failure after radical prostatectomy is controversial and the present study was done to elucidate this point within a prospective phase II on extreme hypofractionation for prostate cancer.

Patients referred for salvage radiotherapy after surgery for pT2-3pN0-x prostate cancer at a single Institution were considered. PSA at biochemical failure had to be higher than 0.2 ng/ml but lower than 2 ng/ml. Patients underwent both mpMRI of the pelvis and PSMA PET/CT. The detection of a discrete lesion within the prostatic fossa was considered the endpoint of the present study. The proportion of patients with positive findings in the two paired groups was compared with the McNemar test, while agreement with Cohen's k test.

107 consecutive patients were accrued from September 2022 to September 2024. The mean PSA value at restaging was 0.53 ng/ml. Overall, 68 patients (63.5 %, 95 %CI: 54.1-72.1 %) were found to harbor at least one lesion in the prostatic fossa; 24 (35.3 %), 4 (5.9 %) and 40 (58.8 %) were detected only by mpMRI, only by PSMA PET/CT and by both tests, respectively. The percentage of discordant pairs was higher than expected (28/68, 41.2 %) and significantly different (p < 0.001). The Cohen's agreement between the two imaging modalities was 0.49, p < 0.001.

mpMRI and PSMA PET/CT show inadequate agreement with the former detecting a significantly higher number of local lesions than the latter with both prognostic and therapeutic implications.

Reducing the overall treatment duration of prostate SBRT has the potential to improve patient comfort and treatment compliance. Additionally, focal boosting to the gross tumor volume (GTV) is of interest to enhance oncologic outcomes. The phase II PROSEVEN trial (MR-guided prostate stereotactic body radiotherapy in seven days) combined both strategies, utilizing MR-guided radiotherapy (MRgRT) to deliver treatment.

Treatment delivered 36 Gy in five fractions to the planning target volume (PTV), 40 Gy to the clinical target volume (CTV), and up to 42 Gy as a simultaneous integrated boost (SIB) to the intraprostatic tumor (GTV). This was administered using a 0.35-Tesla MR-Linac over a seven-day period. The primary endpoint was the incidence of clinician-reported acute GU and GI toxicity of grade 2 or higher, assessed using CTCAE v5.0. Secondary endpoints included patient-reported outcomes (PROMs). This phase II Proseven trial, approved by the Ethics Committee of UZ Brussels, has completed recruitment with five-year follow-up ongoing.

A total of 132 patients with low (12.1 %), intermediate (66.6 %), and limited high-risk (21.2 %) prostate cancer were included. The median PSA at diagnosis was 9.43 ng/ml. SIB to the GTV was performed in 85 % of patients, and 64.4 % completed the treatment within the specified 7 days OTT. No grade 3 acute GU or GI toxicity was observed. Acute Grade 2 GU toxicity occurred in 35 %. Acute Grade 2 GI toxicity occurred in 5 %.

Prostate SBRT with SIB to the GTV in seven days using MRgRT demonstrated acceptable acute GU toxicity rates and low acute GI toxicity.

The use of blood-based risk prediction tools has been proposed to improve prostate cancer screening, but data on repeated screening are lacking. Our aim was to compare outcomes using the blood tests prostate-specific antigen (PSA) and Stockholm3 for repeat prostate cancer screening.

In the population-based screening-by-invitation STHLM3-MRI trial, men aged 50-74 yr were invited to participate in screening. At 2-3 yr after the initial round, men with PSA ≥1.5 ng/ml at trial inclusion who were randomized to magnetic resonance imaging (MRI)-enhanced screening and were not diagnosed with prostate cancer after the initial round were invited for repeat screening involving analysis of PSA and Stockholm3. Biparametric 1.5-T MRI was performed in cases with PSA ≥3 ng/ml or Stockholm3 ≥0.11. Men with Prostate Imaging0Reporting and Data System ≥3 lesions were referred for targeted plus systematic biopsies. The primary outcome was Gleason ≥7 cancer. Secondary outcomes included the number of MRI scans and biopsy procedures, and detection of Gleason 6 and Gleason ≥4 + 3 cancer. Outcomes were compared using the relative positive fractions (RPF). KEY FINDINGS AND LIMITATIONS: Of 7609 men from the initial screening round, 2078 were eligible for repeat screening and 1500 (72%) participated. For detection of Gleason ≥7 prostate cancer, the area under the receiver operating characteristic curve was 0.765 (95% confidence interval [CI] 0.725-0.805) for Stockholm3 and 0.651 (95% CI 0.601-0.701) for PSA. Stockholm3 ≥0.15 was associated with 41% fewer MRI scans in comparison to PSA ≥3 ng/ml (RPF 0.59, 95%CI 0.54-0.64), while the detection of GS ≥4 + 3 cancers was similar (RPF 1.00, 95% CI 0.78-1.29). Stockholm3 ≥0.15 detected fewer Gleason ≥7 (RPF 0.75, 95% CI 0.59-0.95) and Gleason 6 (RPF 0.73, 95% CI 0.46-1.16) cancers. Stockholm3 ≥0.11 was associated with no decrease in the number of MRI scans, but an increase of the number of cancer cases detected. Limitations include the lack of long-term outcomes. CONCLUSIONS AND CLINICAL

Use of the Stockholm3 test for repeated prostate cancer screening could reduce the need for MRI while maintaining detection rates for high-risk cancer. PATIENT SUMMARY: In this study, we invited men to a second round of prostate cancer screening. We found that use of a new blood test called Stockholm3 can make screening programs more efficient by using fewer resources while still detecting aggressive cancers.

The study compares the results of cognitive MRI-ultrasonography fusion prostate biopsy in two positions: left lateral decubitus (LLD) and lithotomy.

From June 2023 to December 2024, 200 patients were randomly assigned to two groups (100 in LLD and 100 in lithotomy). Age, BMI, prostate volume, comorbidities, PSA levels, DRE (+) status, and PI-RADS ≥ 3 lesions were recorded. Pain was measured using the visual analog scale (VAS), and complications were monitored. Histopathological results were collected and analyzed.

No significant differences were found between the groups in terms of age, BMI, PSA, DRE status, prostate volume, comorbidities, or PI-RADS ≥ 3 lesions. Cancer detection rates were 38% in the LLD group and 32% in the lithotomy group (p = 0.550). The average VAS score was lower in the LLD group (2.41 ± 2.30) compared to the lithotomy group (3.22 ± 2.88) (p = 0.030). The mean Gleason score was similar between groups (LLD: 7.05 ± 1.11, Lithotomy: 7.29 ± 1.04; p = 0.247). No major complications occurred, but hematuria was more frequent in the lithotomy group (p = 0.006).

There were no significant differences in cancer detection rates or grades between the two groups. The lithotomy position had slightly higher pain scores but no major complications. Hematuria occurred more often in the lithotomy position. Cognitive MRI-US fusion biopsy is safe in both positions.

As antimicrobial resistance increases, safer alternative approaches to prostate biopsy are needed. PREVENT was a multi-institutional, randomized controlled trial comparing transperineal (TP) biopsy without antibiotic prophylaxis versus transrectal (TR) biopsy with targeted prophylaxis. The authors conducted a secondary cost-effectiveness analysis of PREVENT.

The authors designed a Markov model with a simulated cohort of 1000 biopsied men. They assessed the short-term cost-effectiveness over a 2-week period, comparing relative costs in US dollars and utility measured in quality-adjusted life years (QALYs). The strategies they compared were office-based, magnetic resonance imaging-guided biopsy using two approaches: (1) TP without antibiotics; or (2) TR with targeted antibiotic prophylaxis. Analysis was from a health care payer perspective using a willingness-to-pay (WTP) threshold of $100,000/QALY. Probabilistic sensitivity analysis was performed with 5000 Monte Carlo simulations.

Compared to TR, TP was dominant, offering lower cost and higher utility per patient. This finding was robust to sensitivity analyses with TP having >89% probability of cost-effectiveness regardless of WTP threshold. TP remained dominant when real-world infection rates were used. TP biopsy needed to prevent >0.5% infections compared to TR to maintain cost-effectiveness. Per 1000 patients, TP biopsy prevented 16 infections, and the additional cost to prevent a single infection was $3.18/patient.

In this model, TP biopsy was more cost-effective than TR from a health care payer perspective. In the setting of increasing concerns about the risk of infection from traditional TR biopsy, these findings suggest that office-based TP biopsy is a more cost-effective population-level alternative.

To demonstrate the safety and feasibility of 2-fraction stereotactic body radiation therapy (SBRT) for prostate cancer. METHODS AND MATERIALS: This single-center, noncomparative, phase 2/R-IDEAL 2b trial randomized 46 patients with intermediate/lower high-risk prostate cancer with visible gross tumor volume on multiparametric magnetic resonance imaging to receive 36.25 Gy in 5 fractions over 10 days or 24 Gy in 2 fractions with a gross tumor volume boost up to 27 Gy over 8 days. All treatment was delivered on a magnetic resonance linac with daily adaptive replanning. The primary endpoint was acute grade ≥2 (G2+) genitourinary (GU) toxicity (Common Terminology Criteria for Adverse Events version 5.0). Secondary endpoints include gastrointestinal (GI) toxicity and patient-reported outcomes.

G2+ GU acute toxicity was observed in 6 of 22 patients (27.3%; 95% CI, 0.11-0.50) in the 2-fraction group and 7 of 24 patients (29.2%; 95% CI, 0.13-0.50) in the 5-fraction group. There were no grade 3 GU toxicities. G2+ urinary frequency rose from 4.5% (1 of 22) at week 2 to 13.6% (3 of 22) at week 4 in 2-fraction SBRT. G2+ urinary frequency peaked earlier in 5-fraction SBRT at 16.7% (4 of 24) in week 2, falling to 12.5% (3 of 24) at week 4. At 12 weeks, median Expanded Prostate Cancer Index Composite-26 urinary incontinence score was 85.5 (IQR, 75-100) for 2-fraction SBRT and 100 (IQR, 93.8-100) for 5-fraction SBRT. Urinary irritative-obstructive scores were higher at 12 weeks in the 2-fraction group (93.8; IQR, 87.5-100) than in the 5-fraction group (87.5; IQR, 81.3-93.8). Peak International Prostate Symptoms Score was lower in the 2-fraction group (8; IQR, 4-11) than in the 5-fraction group (13.5; IQR, 10-17). G2+ GI acute toxicity occurred in 3 of 24 (6.8%) after 5-fraction SBRT, but none after 2-fraction SBRT.

Acceptable acute GU toxicity was seen after 2-fraction SBRT. Acute GI toxicity was low. Randomized trials are warranted to explore late toxicity and biochemical control.

Prostate cancer screening is challenged by overdetection, overtreatment, and high resource use. Prostate-specific antigen (PSA) density (PSAD) correlates more strongly with clinically significant cancer than PSA alone. We compare outcomes using various PSAD cutoffs to select men for magnetic resonance imaging (MRI).

STHLM3MRI is a screening-by-invitation trial with 49 118 men invited and 12 750 screened. In the experimental arm, participants with elevated PSA (≥3 ng/ml) had MRI and, if positive [PI-RADS] score ≥3), systematic and targeted biopsies. Evaluated PSAD cutoffs were 0.075, 0.10, 0.125, and 0.15 ng/ml2. Prostate volume was measured by MRI or transrectal ultrasound. The primary endpoint was Gleason ≥3 + 4 cancer detection. The secondary endpoints were Gleason 6 and ≥4 + 3 cancer detection, and the number of MRI scans and biopsies. Relative positive fractions (RPFs) compared the outcomes using PSA ≥3 ng/ml alone. KEY FINDINGS AND LIMITATIONS: Of 7609 men in the experimental arm, 929 (12.2%) had PSA ≥3 ng/ml, and 846 (91%) underwent MRI, with 38% having a PI-RADS score of ≥3. The median prostate volume was 45 ml (interquartile range [IQR], 33-62 ml) and PSAD 0.10 ng/ml2 (IQR, 0.07-0.14 ng/ml2). A PSAD cutoff of 0.075 ng/ml2 reduced Gleason 6 cancer detection by 17% (RPF, 0.83; 95% confidence interval [CI], 0.72-0.96), lowered MRI use by 28% (RPF, 0.72; 95% CI, 0.69-0.75), and missed 5% (RPF, 0.95; 95% CI, 0.92-0.98) of Gleason ≥3 + 4 cancer cases, with no difference in Gleason ≥4 + 3 cancer detection. Higher PSAD thresholds reduced Gleason 6 cancer detection and MRI use, but lowered Gleason ≥3 + 4 cancer detection. Limitations include assumed equivalency between MRI and ultrasound volume. CONCLUSIONS AND CLINICAL

The use of PSAD before MRI lowers overdiagnosis and resource use, while maintaining detection of significant cancer cases. Our results suggest that a PSAD cutoff above 0.075 ng/ml2 is not advisable, regardless of age, due to the increased risk of missing cancer cases with Gleason scores ≥3 + 4.

To assess whether biparametric MRI is noninferior to multiparametric MRI for diagnosis of clinically significant prostate cancer. DESIGN, SETTING, AND

A prospective, multicenter, within-patient, noninferiority trial of biopsy-naive men from 22 centers (12 countries) with clinical suspicion of prostate cancer (elevated prostate-specific antigen [PSA] level and/or abnormal digital rectal examination findings) from April 2022 to September 2023, with the last follow-up conducted on December 3, 2024. INTERVENTIONS: Participants underwent multiparametric MRI, comprising T2-weighted, diffusion-weighted, and dynamic contrast-enhanced (DCE) sequences. Radiologists reported abbreviated biparametric MRI first (T2-weighted and diffusion-weighted), blinded to the DCE sequence. After unblinding, radiologists reported the full multiparametric MRI. Patients underwent a targeted biopsy with or without systematic biopsy if either biparametric MRI or multiparametric MRI was suggestive of clinically significant prostate cancer. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of men with clinically significant prostate cancer. Secondary outcomes included the proportion of men with clinically insignificant cancer. The noninferiority margin was 5%.

Of 555 men recruited, 490 were included for primary outcome analysis. Median age was 65 (IQR, 59-70) years and median PSA level was 5.6 (IQR, 4.4-8.0) ng/mL. The proportion of patients with abnormal digital rectal examination findings was 12.7%. Biparametric MRI was noninferior to multiparametric MRI, detecting clinically significant prostate cancer in 143 of 490 men (29.2%), compared with 145 of 490 men (29.6%) (difference, -0.4 [95% CI, -1.2 to 0.4] percentage points; P = .50). Biparametric MRI detected clinically insignificant cancer in 45 of 490 men (9.2%), compared with 47 of 490 men (9.6%) with the use of multiparametric MRI (difference, -0.4 [95% CI, -1.2 to 0.4] percentage points). Central quality control demonstrated that 99% of scans were of adequate diagnostic quality. CONCLUSION AND RELEVANCE: In men with suspected prostate cancer, provided image quality is adequate, an abbreviated biparametric MRI scan, with or without targeted biopsy, could become the new standard of care for prostate cancer diagnosis. With approximately 4 million prostate MRIs performed globally annually, adopting biparametric MRI could substantially increase scanner throughput and reduce costs worldwide. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04571840.

To assess artificial intelligence (AI)'s added value in detecting prostate cancer lesions on MRI by comparing radiologists' performance with and without AI assistance.

A fully-crossed multi-reader multi-case clinical trial was conducted across three institutions with 10 non-expert radiologists. Biparametric MRI cases comprising T2WI, diffusion-weighted images, and apparent diffusion coefficient were retrospectively collected. Three reading modes were evaluated: AI alone, radiologists alone (unaided), and radiologists with AI (aided). Aided and unaided readings were compared using the Dorfman-Berbaum-Metz method. Reference standards were established by senior radiologists based on pathological reports. Performance was quantified via sensitivity, specificity, and area under the alternative free-response receiver operating characteristic curve (AFROC-AUC).

Among 407 eligible male patients (69.5±9.3years), aided reading significantly improved lesion-level sensitivity from 67.3% (95% confidence intervals [CI]: 58.8%, 75.8%) to 85.5% (95% CI: 81.3%, 89.7%), with a substantial difference of 18.2% (95% CI: 10.7%, 25.7%, p<0.001). Case-level specificity increased from 75.9% (95% CI: 68.7%, 83.1%) to 79.5% (95% CI: 74.1%, 84.8%), demonstrating non-inferiority (p<0.001). AFROC-AUC was also higher for aided than unaided reading (86.9% vs 76.1%, p<0.001). AI alone achieved robust performance (AFROC-AUC=83.1%, 95%CI: 79.7%, 86.6%), with lesion-level sensitivity of 88.4% (95% CI: 84.0%, 92.0%) and case-level specificity of 77.8% (95% CI: 71.5%, 83.3%). Subgroup analysis revealed improved detection for lesions with smaller size and lower prostate imaging reporting and data system scores.

AI-aided reading significantly enhances lesion detection compared to unaided reading, while AI alone also demonstrates high diagnostic accuracy.

The ARGOS-CLIMBER trial is a multi-institutional phase 1/2 study utilizing a combined prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/magnetic resonance imaging (MRI) approach to treat dominant intraprostatic lesions and affected lymph nodes in unfavorable intermediate and high-risk prostate cancer using a 5 fraction SABR and simultaneous in-field boost (SIB) technique. Here we report on the primary endpoint of toxicity within 6 months of treatment. METHODS AND MATERIALS: SIB volumes were defined utilizing a PET/MRI acquired using 18F-PSMA 1007. Five fraction SABR was planned to deliver doses (maximum SIB) to the prostate 35 Gy (50 Gy), seminal vesicles 25 Gy (50 Gy), and lymph nodes 25 Gy (35 Gy) while respecting organs at risk. Toxicity and quality of life (QOL) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 and Expanded Prostate Cancer Index Composite (EPIC-26) during radiation, at 6 weeks posttreatment, and at 6 months posttreatment.

In total, 50 patients were treated, 23 patients had unfavorable intermediate-risk disease, 23 were high risk, and 4 were very high-risk prostate cancer. Median prostate SIB of 41.6 Gy (IQR, 39.3-44.8 Gy) was delivered to a median of 1 intraprostatic lesion. Eighteen patients received nodal treatment. There was a single acute grade 3 gastrointestinal (GI) toxicity of diarrhea and a single late grade 4 GI toxicity of bleeding. With a median follow-up of 12 months, the EPIC-26 scale showed an increase in urinary irritation (P < .001) and no differences for urinary incontinence (P = .12) and GI QOL (P = .65) and a decrease in hormonal/sexual QOL (P < .001 and P < .001). Mean ± SD prostate-specific antigen, maximum standardized uptake value on PET, and maximum MRI Prostate Imaging Reporting and Data System (PIRADS) scores at baseline to 6 months decreased from 15.4 (± 10.3) to 0.18 (± 0.40) ng/mL, 25.5 (± 19.5) to 4.5 (± 7.7), and 4.7 (± 0.6) to 2.9 (± 1.5), respectively.

ARGOS-CLIMBER demonstrated acceptable 6-month toxicity using 5 fraction SABR with PET/MRI directed SIB to the prostate and lymph nodes.

To compare clinically significant prostate cancer (CS-PCa) detection by transperineal (TP) compared to transrectal (TR) magnetic resonance imaging (MRI)-ultrasonography (US) fusion prostate biopsy. PATIENTS AND

Males with abnormal prostate MRI (one or more lesion[s], Prostate Imaging-Reporting and Data System [PI-RADS] score ≥3) consenting to prostate biopsy were enrolled in a randomised control trial (NCT03936127) performed at single-site tertiary care referral centre from October 2022 to June 2024. The patients were randomised to either TP or TR biopsy approach. The primary outcome was CS-PCa (International Society of Urogenital Pathology Grade Group ≥2). Subgroup analysis of the primary outcome was stratified by lesion location (posterior, anterior; and apex, middle, base) and PI-RADS score. Secondary outcomes were detection of any grade PCa, infection, and patient pain score.

In total, 233 patients were randomised (119 patients with 168 lesions in the TP group and 114 patients with 151 lesions in the TR group). CS-PCa was detected in: 61% (73/119; 95% confidence interval [CI] 52-70%) for TP and 54% (62/114; 95% CI 45-64%) for TR (relative risk [RR] 1.13, 95% CI 0.93-1.38, P = 0.23). Adjusted CS-PCa detection rates were higher for TP in anterior lesions: 29% (95% CI 15-49%) vs 16% (95% CI 7-31%) (RR 1.81, 95% CI 1.05-3.12; P = 0.03) and PI-RADS score 4 lesions: 51% (95% CI 39-62%) vs 30% (95% CI 19-43%) (RR 1.77, 95% CI 1.13-2.76; P = 0.01), with no difference in apical lesions (RR 0.91, 95% CI 0.60-1.37; P = 0.65). The median (interquartile range) pain score was 3 (2-4) in the TP group and 2 (1-5) in the TR group (P = 0.09). There were no urinary tract infections or urosepsis events in either group. No patient was withdrawn due to adverse events.

In this trial, we failed to demonstrate a statistically significant, increase in the detection of CS-PCa using TP compared to TR biopsy. There were no sepsis events and biopsy was tolerated in both patient groups. MRI-US fusion prostate biopsy using a TP approach may be more advantageous for anterior and smaller lesions, higher powered studies are needed.

Focal salvage high dose-rate (HDR) prostate brachytherapy has emerged as a standard option for radiorecurrent prostate cancer. However, long-term prospective data remains limited. Our prospective study aimed to explore the toxicities, health-related quality of life (HRQOL) and efficacy of focal salvage HDR prostate brachytherapy. This report represents the updated results of the final cohort of patients.

Patients with biopsy-confirmed, MR-visible local recurrent prostate cancer after previous external-beam radiotherapy (XRT) and/or brachytherapy were eligible. MR-assisted, ultrasound-based focal HDR prostate brachytherapy with a prescription dose of 27 Gy in 2 fractions separated by 1-2 weeks apart was delivered. Adjuvant androgen deprivation therapy (ADT) was not used.

59 patients were enrolled in the study. Median follow up from salvage HDR was 54 months (11-132). The initial treatment was XRT only in 20 (34 %) and brachytherapy +/- XRT in 39 (66 %). The pre-HDR median PSA was 4.13 ng/mL (1.30-11.63). Twenty-five (42 %) were staged with a PSMA PET scan. One patient (1.7 %) required temporary urinary catheterization. There was only 1 grade 3-5 toxicity, a late grade 3 GU toxicity. Three-year biochemical failure-free survival and freedom from ADT or repeat salvage therapy rate was 54 % and 82 %, respectively. Of the 55 patients who had a post-HDR MRI (median 464 days), 46 (84 %) patients had a complete response and 9 had persistent disease. 8 (15 %) patients recurred elsewhere in the prostate.

Our toxicity and PSA failure-free results suggest that focal gland salvage HDR brachytherapy is well tolerated and effective. CLINICALTRIALS: gov identifier NCT01583920.

To evaluate [18F]F-DCFPyL PET/MRI whole-gland-derived radiomics for detecting clinically significant (cs) prostate cancer (PCa) within the prostate gland and predicting extra-prostatic metastasis (N and M staging).

In this single-centre, retrospective study, therapy-naïve PCa patients who underwent [18F]F-DCFPyL PET/MRI were included. Whole-prostate segmentation was performed. Feature extraction from each modality was done. The selection of potential variables was made through regularized binomial logistic regression. The oversampled training data were used to train binomial logistic regression for each outcome. The estimates of the models were calculated, and the mean accuracy was reported. The trained models were assessed on the test data for comparative evaluation of performance.

A total of 103 patients (mean age = 65; mean PSA = 23.4) were studied. Among them, 89 had csPCa and 20 had metastatic disease. There were five radiomics variables selected for the International Society of Urological Pathology Grade Group (ISUP GG) ≥ 2 from T2w, ADC, and PET. To detect N1, five radiomics variables were selected from the T2w and PET. For M1, four radiomics variables were selected from T2w and ADC. Regarding the performance of models for the prediction of csPCa, the imaging-based hybrid model (T2w + PET) provided the highest AUC (0.98). The performance of N1 models showed the highest AUC (0.80) for T2w + PET. To predict M1, the T2w + ADC model showed the highest AUC (0.93).

Whole-gland PET/MRI radiomics may provide a reliable model to predict csPCa. Also, acceptable performance was reached for predicting metastatic disease in our limited population. Our findings may support the value of whole-gland radiomics for non-invasive csPCa detection and prediction of metastatic disease. ADVANCES IN KNOWLEDGE: Whole-gland PET/MRI radiomics, a less operator-dependent segmentation method, can be potentially used for treatment personalization in PCa patients. TRIAL REGISTRATION: NCT03535831. Registered 2018; NCT03149861. Registered 2017.

A biomarker to help predict outcomes after prostate cancer (PCa) focal therapy would be of considerable interest. We sought to assess the association between treatment failure after focal therapy and the Decipher score, a tumor-based genomic classifier (GC).

We performed a post hoc analysis of a single-center phase II trial (ClinicalTrials.gov identifier: NCT03503643) in which patients with unilateral grade group (GG) 2-4 PCa (n = 108) underwent hemigland cryoablation of the prostate (2017-2021; n = 108). Pretreatment biopsy tissue was subjected to transcriptomic profiling to generate GC scores. The primary outcome was the association between GC-low (<0.45) versus GC-high (≥0.45) and in-field recurrence (GG ≥2) on magnetic resonance imaging-guided biopsy 6 months post-treatment, evaluated using multivariable logistic regression.

In the GC-high group (n = 37), treatment failure occurred in 17 patients (46%). In the GC-low group (n = 71), treatment failure occurred in 15 patients (21%). These differences were statistically significant (odds ratio [OR], 2.61 [95% CI, 1.05 to 6.51]; P = .04). Differences at 18 months were also significant (76% v 44%; OR, 3.58 [95% CI, 1.37 to 9.36], P = .009).

In patients with PCa otherwise suitable for management with focal therapy, a high GC score (≥0.45) was independently associated with treatment failure. A GC score derived from diagnostic biopsy can be used to help predict focal therapy outcomes.

Prostate biopsy (PBx) is crucial for diagnosing prostate cancer (PCa). This study aims to identify potential underdiagnosis of transition zone (TZ) PCa compared with peripheral zone (PZ) tumors and validate a novel PBx strategy to improve TZ tumor detection.

This study comprised two components: a retrospective analysis and a randomized clinical trial. The retrospective study included 217 patients who underwent radical prostatectomy after 8PZ + 4TZ + X transperineal transrectal ultrasound-magnetic resonance imaging-fusion PBx between 2018 and 2021. The clinical trial investigated biopsy efficacy in 400 patients who underwent either modified 8PZ + 10TZ + X PBx for the TZ lesion or 8PZ + 4TZ + X PBx after block random assignment between 2022 and 2023 at our center.

Retrospective analysis reveals identical TZ clinically significant prostate cancer (csPCa) detection rates for 8PZ + 4TZ + X and 4TZ + X PBx, both of which were insufficient for detecting TZ csPCa compared with PZ tumors. Based on these findings, 8PZ + 10TZ + X PBx was constructed. In the trial, the 10TZ + X and 8PZ + 10TZ + X PBx demonstrated identical TZ csPCa detection rates and biopsy positivity rate, outperforming the 4TZ + X and 8PZ + 4TZ + X PBx without increasing complications. The self-controlled comparison showed equivalent results for 8TZ + X and 8PZ + 10TZ + X PBx.

Our study found that PZ biopsies offer no additional benefit for TZ lesion tumors, and increasing the number of cores in the TZ region can compensate for the current limitations of TZ biopsies. These findings provide potential avenues for optimizing biopsy strategies for TZ lesions.

Recent advances in high-performance gradient technology have enabled shorter echo times (TEs) for diffusion-weighted prostate MRI. Short TE may improve the conspicuity of the usually T 2 hypointense lesions but may also influence the diagnostic performance of the apparent diffusion coefficient (ADC) due to a changed weighting of subcompartments, including prostate fluid and tissues. The purpose of this study was to evaluate the influence of TE on prostate diffusion-weighted images with respect to lesion conspicuity and diagnostic performance of the ADC.

This institutional review board-approved prospective monocentric study included n = 55 (mean age 69 ± 9 years) patients undergoing clinically indicated prostate MRI on two 3 T MRI scanners with high-performance gradients. Diffusion-weighted imaging (DWI) was performed with an echo-planar sequence at 2 different TEs, 41 ms and 70 ms, with b-values of 50 s/mm 2 and 800 s/mm 2 . Computed DWI was generated for a b-value of 1400 s/mm 2 . The lesion conspicuity and image quality were rated by 3 independent readers with a 5-point Likert scale and tested with the Wilcoxon rank sum test. Lesion ADCs were recorded, and their ability to detect significant lesions (Gleason score >6) was assessed with a receiver operator curve analysis.

Among the participants, n = 24 had clinically significant prostate cancer. The image quality at b  = 1400 s/mm 2 was rated significantly higher at TE = 41 ms than at TE = 70 ms (mean Likert score ± standard deviation for TE = 41 ms vs TE = 70 ms: R1: 4.06 ± 0.68 vs 3.02 ± 0.59; R2: 4.09 ± 0.82 vs 3.26 ± 0.67; R3: 4.16 ± 0.71 vs 3.18 ± 0.70; for all P 's < 0.001). The lesion conspicuity at b  = 1400 s/mm 2 was rated higher at TE = 41 ms than at TE = 70 ms (mean Likert score ± standard deviation for TE = 41 ms vs TE = 70 ms: R1: 4.55 ± 0.66 vs 4.46 ± 0.72, P  = 0.17; R2: 4.64 ± 0.59 vs 4.53 ± 0.63, P  = 0.03; R3: 4.53 ± 0.66 vs 4.28 ± 0.80, P  = 0.01). However, the ADC-based area under the curve for lesion characterization decreased from 0.80 at TE = 70 ms to 0.70 at TE = 41 ms ( P  = 0.07).

Shortening TE to 41 ms in prostate DWI increases lesion conspicuity on high b-value images; however, it negatively impacts the diagnostic performance of the ADC.

To prospectively compare the ability of 18F-PSMA-1007 PET/CT and whole-body MRI (WBMRI) with DWI to detect prostate cancer (PCa) lesions and assess their local stage. Additionally, to evaluate the correlation between PSMA uptake on PET/CT and PSMA expression as assessed by immunohistochemistry.

Men with newly diagnosed unfavourable intermediate or high-risk PCa underwent 18F-PSMA-1007 PET/CT and WBMRI with DWI before robot-assisted laparoscopic prostatectomy. Diagnostic accuracy for intraprostatic tumour localization, seminal vesicle invasion (SVI), and extraprostatic extension (EPE) was evaluated using whole-mount prostatectomy specimens as the reference standard. SUVmax was compared with immunohistochemical PSMA staining intensity quantified using QuPath software.

19 patients with 39 intraprostatic lesions in histopathology were included. The overall lesion detection rates for PET/CT were 84.6% and 82.1% for two independent readers, compared to 74.4% and 46.2% for MRI readers. The detection rates of index lesions were 94.7% for PET/CT and 74.0-84.0% for MRI, whereas those of non-index lesions were 70.0-75.0% for PET/CT and 20.0-65.0% for MRI. For detecting EPE, AUC values were 0.500-0.591 for PET/CT and 0.648-0.682 for MRI. For detecting SVI, AUC values ranged from 0.629 to 0.700 across both modalities. SUVmax showed a weak correlation with immunohistochemical expression of PSMA multiplied by lesion diameter (Spearman's ρ = 0.427, p = 0.013). Lesion diameters measured using 30% and 40% of SUVmax, as well as prostate SUVbackground x2, showed the closest agreement with histopathological measurements.

18F-PSMA-1007 PET/CT demonstrated high sensitivity in localizing intraprostatic carcinoma lesions but seemed inferior to WBMRI in detecting EPE. PSMA uptake appears to depend on both PSMA expression and lesion size. These findings highlight the complementary roles of PET/CT and MRI in the detection and tumor staging of PCa. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03537391. Registered 25 May 2018.

Up to 50% of clinical recurrences after curative-intent prostate cancer radiation are intraprostatic radiorecurrences (IPRRs). Salvage local therapy (SLT) is increasingly offered, particularly as focal SLT, to reduce toxicity due to prior radiation. Limited data exist on the relative value of magnetic resonance imaging (MRI), positron emission tomography/computed tomography (PET/CT), and biopsy on SLT target delineation. We compared MRI, PET/CT, and biopsy in patients with IPRRs and the impact each modality has on identifying IPRRs and defining the extent of prostatic involvement. METHODS AND MATERIALS: We performed a secondary analysis of 62 patients enrolled in a phase 1/2 clinical trial of salvage high-dose-rate brachytherapy. The IPRR was delineated using each imaging modality and by defining the involved regions of the prostate on biopsy. The exact binomial distribution was used to estimate the sensitivity of MRI and PET/CT to detect the IPRR. Exact conditional logistic regression was used to compare the tumor identified by MRI and PET/CT with the areas of biopsy involvement (gold standard) and estimate the proportion of patients with prostatic involvement outside of the image-defined targets.

The sensitivity for detecting the IPRR was 91.8% for MRI and 85.5% for PET/CT. Most patients had biopsy-proven cancer outside of the MRI-defined (70.5%) and PET/CT-defined (73.8%) target. Delineating the brachytherapy target using imaging only would have missed the full extent of recurrence in 63.9%.

Although MRI and PET/CT are valuable, a thorough biopsy is a mandatory tool to avoid missing areas of imaging-occult prostatic involvement when delivering focal SLT.

To evaluate the efficacy of adding a simple prostate mapping diagram to multiparametric prostate magnetic resonance imaging (mpMRI) reports, a randomized, prospective study is designed. Despite cognitive prostate biopsy is the most preferred approach among targeted biopsy methods due to its low cost and easy application, its operator dependency requires standardization to improve diagnostic accuracy for prostate cancer (PCa).

A total of 155 patients underwent mpMRI as the standard of care and were randomly assigned in a 1:1 ratio to two groups: prostate mapping diagram and standard group. In addition to the mpMRI reports, suspicious lesions (≥PI-RADS 3) were drawn on a schematic diagram by a single specialized uro-radiologist in the prostate mapping group. A single experienced urologist sampled four cores from each target in addition to a 12-core systematic biopsy in both groups. A Gleason score of 3+4 or higher was considered as clinically significant PCa (csPCa).

Overall cancer detection rate between the group 1 and 2 was statistically significant (57% and 35%, respectively, P=.006). Particularly, csPCa rates among the groups were 47% (36/77) and 21% (16/78) for group 1 and group 2, respectively (P<.001). The csPCa detection with only targeted biopsies was strikingly as high as 3-fold (17% vs 6%, P=.048) in the mapping group.

Our prospective study has shown that the addition of a simple mapping strategy to mpMRI reports significantly increased cancer rates by cognitive biopsy. We strongly recommend the use of a schematic mapping diagram in biopsy protocols.

To present the primary endpoint results, toxicities and quality of life (QoL) after two-year follow-up (FU) of the HypoFocal Phase II trial.

Intermediate- and high-risk prostate cancer (PCa) patients were treated with moderately hypofractionated radiotherapy (MHRT) of 60 Gy in 20 fractions and a focal-boost of up to 75 Gy in Arm A, or high-dose-rate-brachytherapy (HDR-BT) of 15 Gy to the whole-gland with a boost of up to 19 Gy, followed by external beam RT (EBRT) of 44 Gy in 20 fractions in Arm B. Boost was based on combined information by multiparametric-magentic-resonance-tomography (mpMRI) and positron-emission-tomography targeting prostate-specific-membrane-antigen (PSMA-PET). Genitourinary (GU) and gastrointestinal (GI) toxicities were assessed according to CTCAEv5.0. QoL was assessed with validated questionnaires (IPSS, QLQ-PR25 and QLQ-PR30).

Twenty-five patients were treated with MHRT and 30 patients with HDR-BT + EBRT. At two-year-FU, the rate of grade 2 + GU and GI toxicity was 24 % and 8 % in Arm A and 10 % and 0 % in Arm B, respectively. Two grade 3 GI toxicities were reported in Arm A, which can be attributed to multifactorial genesis and interventions. QoL was good with significant and minimally-important-differences only in bowel symptoms in Arm A and sexual functioning in Arm B. One patient in each arm relapsed. Limitations are the relatively small sample size.

This is the first trial do demonstrate safety and feasibility of focal dose-escalation based on mpMRI and PSMA-PET in MHRT and HDR-BT + EBRT in intermediate- and high-risk PCa. Particularly, HDR-BT offers good toxicity and QoL profiles. Radiation proctitis demands careful management.

To investigate the diagnostic value of magnetic resonance imaging (MRI) for persistent prostate cancer after irreversible electroporation (IRE) therapy. PATIENTS AND

This is a post hoc analysis from a multicentre randomised trial, in which men with localised low- to intermediate-risk prostate cancer were randomised to receive either focal or extended IRE ablation. All patients underwent repeat MRI scans at 6 and 12 months and transperineal template mapping biopsy (TMB) at 6 months post-IRE. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MRI were calculated for infield and outfield lesions using 2 × 2 contingency tables with 95% confidence intervals (CIs) for clinically significant prostate cancer and any-grade prostate cancer.

A total of 106 patients were recruited to this study, including 39 patients (37%) with clinically insignificant prostate cancer and 67 patients (63%) with clinically significant prostate cancer (International Society of Urological Pathology grade ≥2). Of these, 101 patients underwent repeat MRI scan and prostate biopsy at 6 months after IRE. The rate of clinically significant prostate cancer detected by TMB infield and outfield was 9.9% (10/101) and 9.9% (10/101), respectively. In the treated area, the sensitivity, specificity, PPV and NPV for MRI to detect clinically significant prostate cancer were 30% (95% CI 6.7%-65%), 91% (95% CI 82%-96%), 27% (95% CI 6.0%-61%) and 92% (95% CI 84%-97%), respectively. In the untreated area, the sensitivity, specificity, PPV and NPV of MRI to detect clinically significant prostate cancer were 20% (95% CI 2.5%-56%), 91% (95% CI 82%-96%), 20% (95% CI 2.5%-56%) and 91% (95% CI 82%-96%), respectively.

Favourable specificity but poor sensitivity was achieved with use of MRI to detect persistent clinically significant prostate cancer after IRE treatment. Repeat TMB should not be deferred, regardless of MRI results.

Targeted microwave ablation (TMA) is a novel modality of focal therapy to treat localized prostate cancer (PCa). We evaluated its short-term functional and oncologic outcomes.

We performed a single-center, prospective, interventional phase I-II pilot trial (NCT04627896). TMA was performed in 11 patients with a single intracapsular MRI-visible lesion ≤12 mm, International Society of Urological Pathology (ISUP) grade ≤ 2, Prostate Specific Antigen (PSA) < 20 ng/mL, and a 5-mm safety distance from apex and rectum. Patients were treated with a 12 W very low-loss microwaves ablation system, guided by 3D ultrasound/MRI fusion imaging. Follow-up consisted in clinical visits, PSA and validated questionnaires. MRI was scheduled at five months and rebiopsy at six months. The primary endpoints of study were safety and efficacy (absence of tumour in the treated area).

No severe complications were reported. All patients were discharged the same day of treatment without bladder catheter. No significant changes in PSA or questionnaires scores were reported. At rebiopsy, no cancer was found in five patients (45%); eight patients (73%) had an absence of in-field PCa and nine patients (82%) had an absence of in-field ISUP ≥ 2 PCa. New cancer foci outside the treated area were found in three patients (27%). Limitations of this study were the very limited sample size, the short follow-up, and the lack of a comparator.

TMA guided by fusion imaging is a safe modality with good ablative efficacy.

PSMA PET offers the potential for improved local staging prior to radical prostatectomy (RP). We evaluated PSMA PET versus mpMRI for local and nodal staging for patients with localized NCCN high or very high risk prostate cancer undergoing RP.

A prospective single center pilot study was conducted from 9/2018 to 6/2022. Patients underwent both mpMRI and 18F-DCFPyL PSMA PET with limited MRI sequences, followed by RP with pelvic lymphadenectomy. Patient and side-specific performance of mpMRI and PSMA PET were compared to RP histopathological standard of truth for extraprostatic extension (EPE), seminal vesicle invasion (SVI), and lymph node involvement (LNI).

At RP, 79% (38/48) had EPE, 31% had SVI, and 31% had LNI. At the patient level for EPE, PSMA PET had similar sensitivity (65.8% vs. 84.2%, respectively, P = 0.07) but higher specificity (80% vs. 40%, P = 0.045) compared to mpMRI, respectively. For SVI, PSMA PET had lower sensitivity (62.5% vs. 87.5%, P = 0.046) and similar specificity (87.5% vs. 90.6%, P = 0.56). For side-specific LNI, PSMA PET had higher sensitivity (50% vs. 25%, P = 0.03) and similar specificity (96.1% vs. 94.7%, P = 0.71) compared to mpMRI.

PSMA PET offers higher specificity for EPE and higher sensitivity for LNI compared to mpMRI. PSMA PET may improve overall surgical planning, and may be combined with diagnostic mpMRI and clinicopathological variables through nomograms to further predict EPE, SVI, or LNI. CLINICAL TRIAL REGISTRATION: NCT03392181 https://clinicaltrials.gov/study/NCT03392181 .

To improve precision of secondary resection (SR) after positive surgical margin (PSM) detection by frozen section (FS) during nerve-sparing (NS) robot-assisted radical prostatectomy (RARP) by employing a personalised three-dimensional (3D)-printed prostate model derived from pelvic magnetic resonance imaging (MRI). This model was used to mark positive surgical margins (PSM) and guide intraoperative SR during NS-RARP. PATIENTS AND

Prospective multicentre cohort study with 100 patients undergoing NS-RARP between September 2018 and August 2021. Primary and secondary endpoints were the conversion rate of FS-identified PSM to a tumour-free margin and functional/oncological parameters within a 12-month follow-up, respectively.

A PSM was identified in 23% of cases during FS, with a conversion to negative surgical margins (NSM) in 83% (19/23 cases) by model-guided SR. The tumour detection rate in SR specimens was 39% (nine of 23 cases). Among the 19 patients with converted margins, 18 (95%) achieved undetectable prostate-specific antigen levels 2 months postoperatively, with six (32%) having subsequent biochemical recurrence within 12 months. prostate-specific-membrane-antigen positron emission tomography computed tomography found one local recurrence, and five cases of metastatic disease. In converted patients, the baseline median five-item version of the International Index of Erectile Function score decreased by 16% after 1 year, with no significant difference compared to patients with primarily NSM. Limitations include the absence of a control group, the potential for false-negative FS results and limited accuracy of MRI.

The integration of 3D-printed prostate models into NS-RARP has the potential to positively impact surgical outcomes by improving the precision of SR and optimising pathosurgical communication.

The optimal biopsy strategy in prostate cancer screening is unknown. This study aims to assess the diagnostic effects of omitting systematic biopsies in a screening cohort.

We used data from the STHLM3-MRI trial. A total of 7609 men aged 50-74 yr were randomised to undergo magnetic resonance imaging (MRI) if having an elevated risk of prostate cancer (prostate-specific antigen [PSA] ≥3 ng/ml or Stockholm3 ≥11%). Participants with Prostate Imaging Reporting and Data System (PI-RADS) ≥3 underwent targeted and systematic biopsies. Cancer detection rates from combined and targeted-only biopsies were presented as a risk ratio (RR). Subgroup analyses were stratified by age, PSA density (PSAd), and PI-RADS. Differences in reclassification rates at radical prostatectomy were calculated. KEY FINDINGS AND LIMITATIONS: The median age of the participants was 66 yr (interquartile range: 61-71) and PSA 3.8 ng/ml (2.9-5.8). Out of 395 men undergoing combined biopsies, 52 (13.2%) had International Society of Urological Pathology (ISUP) grade group (GG) 1 and 230 (58%) had ISUP GG ≥2 prostate cancer. Omission of systematic biopsies reduced cancer detection rates (RR of ISUP GG 1: 0.83 [95% confidence interval 0.64-1.07]; ISUP GG ≥2: 0.85 [0.81-0.90]; and ISUP GG ≥3: 0.86 [0.79-0.95]). Each case of averted ISUP GG 1 cancer was associated with 3.8 cases of missed ISUP GG ≥2 and 1.1 case of ISUP GG ≥3 cancer. Detection of fewer ISUP GG ≥2 cases than the number of avoided ISUP 1 cancer cases was observed in all subgroups when systematic biopsies were omitted. Using PSAd ≥0.05 ng/ml2 as a cut-off for a biopsy resulted in the same numbers of ISUP GG 1 tumours saved, with higher detection rates of ISUP GG ≥2 tumours. In 146 men undergoing radical prostatectomy, 46 (31.5%) versus 28 (19.2%) were upgraded following targeted biopsies versus a combined biopsy strategy (p < 0.05). CONCLUSIONS AND CLINICAL

Complete omission of systematic biopsies in prostate cancer screening is associated with decreased detection of significant cancer, while reducing overdetection of insignificant cancer to a smaller extent. This strategy also increased the risk of histopathological misclassification. PATIENT SUMMARY: In a prostate cancer screening setting, we examined the diagnostic effects of systematic biopsies in addition to targeted biopsies in men with suspicious magnetic resonance imaging lesions. We found that exclusion of systematic biopsies led to reduced detection of clinically significant prostate cancer. Our findings emphasise the importance of incorporating systematic biopsies alongside targeted biopsies for improved diagnostic outcomes.

Active surveillance (AS) is the preferred management strategy for low-risk prostate cancer. This study aimed to evaluate the impact of Habitat Risk Score (HRS), an automated approach for mpMRI analysis, for early detection of progressors in a prospective AS clinical trial (MAST NCT02242773).

The MAST protocol includes Confirmatory mpMRI ultrasound fusion (MRI-US) biopsy and yearly surveillance MRI-US biopsies for up to 3 years. Clinical and mpMRI data from patients that progressed based on protocol criteria at years 1-3 were reviewed. Patients were classified as "MRI/HRS Progressors" if the PI-RADS lesion(s) had been targeted throughout the surveillance and resulted in positive biopsies, or as "Missed Progressors" if the lesion(s) were not identified by PI-RADS ("PI-RADS Miss") or were missed by the biopsy ("Needle Miss"). HRS maps were generated for each patient and evaluated for association with histopathological progression.

Of the 34 patients, 15 were classified as "MRI/HRS Progressors" and 19 as "Missed Progressors" (12 "PI-RADS Miss", seven "Needle Miss"). In all cases, HRS confirmed the PI-RADS assessment. In the "PI-RADS Miss" group, HRS identified the lesions in all patients that were not targeted by biopsy and resulted in patient reclassification. HRS volumes showed clear association with tumor evolution both in terms of volume and aggressiveness over time.

HRS volumes can serve as a quantitative biomarker for early detection of progression and lead to timely conversion to treatment, thereby improving patient outcomes and reducing the burden of unnecessary surveillance.

Our goal was to determine whether the difference between MRI-based and ultrasound (US)-based volume measurements are associated with MRI/US-targeted fusion-guided biopsy outcomes.

This retrospective, single-center study involved 4177 consecutive patients biopsied between 2010 and 2023 using both MRI/US-targeted fusion and systematic biopsy. Biopsies were indicated because of elevated PSA levels or abnormal multiparametric MRI results. US volume measurements were calculated using the triplane ellipsoid formula, and MRI volumes were obtained by semiautomatic planimetric segmentation. Performance of fusion biopsy compared with systematic biopsy was analyzed with respect to the discordance between MRI and US volume measurements.

In 2736 patients (66%), biopsy detected prostate cancer. In cases where both techniques yielded prostate cancers (1695/2736 [62%]), a statistically higher proportion of patients had higher Gleason scores on MRI/US-targeted fusion biopsy compared with systematic biopsy (343 patients [20.2%] vs 137 patients [8.1%], P < .001). MRI volume measurements were significantly smaller compared with US volume measurements (median [IQR] 54 mL [39-77], 56 mL [40-80], respectively, P < .001). Beyond 5 mL volume discordance, MRI/US-targeted fusion biopsy gradually showed less added diagnostic benefit compared with systematic biopsy. In the ≤ 5 mL cohort, MRI/US-targeted fusion biopsy detected more aggressive tumors in 4 times as many patients as systematic biopsy (136 vs 32 patients, P < .001).

Although MRI/US-targeted fusion biopsy detected more prostate cancers than systematic biopsy, the performance of MRI/US-targeted fusion biopsy declined with more discordance between volumes measured in MRI vs US. Awareness of volume discordance in MRI- and US-based volume measurements should alert the operator about the possibility of reduced performance of MRI/US-targeted fusion biopsy.

Focal therapy (FT) is an emerging option for intermediate-risk prostate cancer (IR-PCa). Transperineal MRI fusion laser ablation of PCa (TPFLA) is a novel FT technique with limited data reported. We conducted a phase I clinical trial evaluating the safety, feasibility, and 1-year oncologic results for patients with IR-PCa treated with TPFLA in an office setting.

NCT05241236 aimed to evaluate TPFLA for the International Society of Urological Pathology-grade 2 (ISUP-2) tumors. All procedures were performed in the office using MR/US fusion imaging. The diode interstitial laser system fibers were applied through the perineum using local anesthesia. The primary outcome was safety and tolerability. Pain scores were recorded using analog scales. Thirty-day adverse events and 1-year prostate biopsy oncologic outcomes were noted. Functional outcomes at 3 months and 1 year were compared with baseline as well.

Thirty patients accrued had TPFLA safely in the office with no complications. TPFLA median pain score was 1. At 30 days, one man required a transurethral resection of the prostate (TURP). There were no imaging demonstrable cancers at 3 months and a significant improvement in urinary function (p = 0.001) was noted and sustained for the year. No patient experienced urinary incontinence. No changes in sexual function were observed (p = 0.7). At 1 year, 25/30 (83%) had no clinically significant cancer. However, 14 had PCa, in 5 (17%) solely in treated areas, all ISUP-1. Seven had PCa outside the treated areas. Two had infield and outfield recurrences, both were ISUP 2. At study closure, 16 patients were free from PCa, 3 were on active surveillance, 9 were treated focally with cryoablation, and 2 were converted to radical surgical procedure.

TPFLA appears to be a safe and an effective focal therapy for IR-PCa, offering a potential alternative to more radical treatments with a minimal periprocedural impact. Longer follow-up and larger studies are needed to confirm these results.

To evaluate MRI-based measurements of androgen-sensitive perineal/pelvic muscles in men with prostate cancer before and after androgen deprivation therapy (ADT) as a novel imaging marker for end-organ effects of hypogonadism. Diagnosing hypogonadism or testosterone deficiency (TD) requires both low serum testosterone and clinical symptoms, such as erectile dysfunction and reduced libido. However, the non-specific nature of many TD symptoms makes it challenging to initiate therapy. Objective markers of TD help to better identify patients who may benefit from testosterone supplementation; however, current markers, such as low bone mineral density, lack sensitivity. Previous studies suggest that decreased bulbocavernosus-muscle (BCM) thickness may be associated with TD, although it remains unclear if this is a correlative relationship.

Data were prospectively collected for patients with intermediate/high-risk localized prostate cancer enrolled in a phase II trial (NCT02430480). Patients received ADT before prostatectomy and underwent prostate MRI pre-/post-ADT. BCM, ischiocavernosus-muscle (ICM), and levator-ani-muscle (LAM) measurements were made using T2W-MRI. Paired t-tests evaluated changes in BCM/ICM/LAM width, and linear regression analyses evaluated relationships between changes in testosterone and muscle width.

Thirty-eight consecutive patients with pre-/post-ADT MRIs were analyzed. Baseline testosterone was 286.5ng/dL, and 36/38 patients had post-ADT testosterone <50ng/dL. Pre-ADT and post-ADT measurements of the bilateral BCM/ICM/LAM width were 7.16mm/7.95mm/5.53mm and 5.68mm/6.71mm/4.89mm, respectively (P <.001). Decreases in testosterone predicted reduction in combined perineal muscle (BCM+ICM) width (P = .032).

Androgen deprivation led to significant and relatively rapid decreases in BCM/ICM/LAM thickness. This objective biomarker of low testosterone states may help identify patients who will potentially benefit from testosterone replacement.

The purpose of this study was to assess safety and feasibility of percutaneous magnetic resonance-guided placement of an implantable microdevice (IMD) to evaluate in situ intratumor response to multiple pharmacologic agents in men with intermediate-risk and high-risk localized prostate cancer.

Biocompatible IMDs measuring 750 µm in diameter and 5 mm in length were prepared with 20 reservoirs containing candidate drug and drug combinations including second-generation androgen inhibitors, PARP inhibitors, PD-1 inhibitors, and conventional chemotherapy. Men with intermediate-risk or high-risk localized prostate cancer and MRI-visible lesions were enrolled. Up to 4 IMDs were placed using a transperineal approach into MRI-visible tumors 2 days before planned radical prostatectomy. After radical prostatectomy, the IMDs and a small segment of surrounding tumor tissue were removed and sectioned, stained, and analyzed for tissue drug response by a variety of pharmacodynamic markers.

Fourteen patients were enrolled: 7 (50%) with intermediate-risk and 7 (50%) with high-risk localized prostate cancer. A total of 53 IMDs were implanted (mean 3.8 per patient), and 49 IMDs (92%) were successfully retrieved. All men underwent uncomplicated robotic-assisted radical prostatectomy and bilateral pelvic lymph node dissection 2 days after IMD placement. There were no severe adverse events. Pathological examination of the tissues adjacent to the IMDs demonstrated differential drug response within patients and between patients. Limitations include small sample size.

A multidrug IMD can be safely placed percutaneously into MRI-visible lesions before radical prostatectomy, enabling assessment of tumor-specific local response to multiple agents simultaneously within the tumor's normal stromal environment to guide targeted systemic therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04399876.

To investigate the effect of using three-dimensional (3D) modeling before the surgery on positive surgical margins (PSM) in patients who underwent radical retropubic prostatectomy (RRP).

A prospective data analysis of 81 patients who underwent RRP between April 2021 and December 2023 was performed. Patients were randomized into 2 groups. In "3D group" (n:41), patients were evaluated by the surgeon and radiologist by using a 3D modeling of the mpMRI images which were done by two experienced radiologists just before the surgery. In "non-3D group" (n:40), the surgeon evaluated the mpMRI scans and reports by himself without a 3D modeling of the mpMRI before the operation. Finally, positive surgical margins of two groups were compared.

The mean age of the patients was 66.7 ± 5.2 and 65.3±4.9 years in 3D group and non-3D group, respectively. (p = .65) Preoperative PSA value, prostate volume, preoperative PIRADS 4 and PIRADS 5 scores, postoperative ISUP grades and T stages were statistically similar in both groups. (p > .05) The PSM rate was 24 (29.6%) in the overall patient population. PSM was detected in 6 (14.6%) and 18 (45%) of the patients in 3D group and non-3D group, respectively. (p = .005)

Using a 3D modeling of the mpMRI images before the surgery decreased the PSM rates after radical retropubic prostatectomy. The present study also reveals the importance of collaboration between radiologists and urologists in the accurate preoperative evaluation of prostate cancer.

Prostate cancer remains a significant public health challenge, an early detection with prostate-specific antigen (PSA) testing and biparametric MRI (bpMRI) can improve outcomes. However, participation hinges on motivational, psychological, and logistical factors. This study examines the motivational profile of men in the ProstaPilot study to guide strategies to increase uptake of state-of-the-art prostate cancer screening programs.

The ProstaPilot study enrolled 423 men who underwent both PSA testing and bpMRI of the prostate. Positive results (PSA ≥ 3 μg/L or PI-RADS 4-5 lesions) were referred for further urological examination and biopsy. Using an exploratory correlational design, 360 participants completed a detailed questionnaire. Motivational factors were extracted via Principal Component Analysis (PCA) with Oblimin rotation. Perceptions of prostate cancer risk, severity, and prevention were rated on 1-10 scales (10 = most positive).

PCA identified four motivational factors explaining 55.6% of variance: (1) concerns about screening (e.g., unnecessary surgery, loss of control); (2) perceived benefits of early detection; (3) social motivation (e.g., contributing to research, role modeling); and (4) barriers (e.g., logistics, embarrassment). Over half (51.1%) had not considered screening before ProstaPilot; others decided over varying timeframes. Participants showed high awareness of prostate cancer and valued early detection, rating screening effectiveness 9.55 ± 0.98 and trust in healthcare professionals 9.6 ± 1.0. Social/familial influences were moderate. Satisfaction was high: likelihood to recommend 9.45 ± 1.22; confidence in continuing participation 9.9 ± 0.39.

Highly motivated participants were marked by strong knowledge of prostate cancer screening, trust in healthcare providers, supportive social context, and high personal commitment. These findings support personalized, socially supportive, educational strategies to increase uptake of state-of-the-art screening. CLINICAL TRIAL REGISTRATION: The study was registered on September 21, 2024, with the identifier number NCT05603351.

SABR-Dual is a phase-III trial with an initial phase-I safety cohort, of 2-fraction stereotactic radiotherapy (SABR) with optional magnetic resonance imaging (MRI)-based focal boost, using peri-rectal spacing, for localized prostate cancer. This represents the initial report from the phase-I non-randomized cohort. METHODS AND MATERIALS: Subjects had favorable intermediate risk (FIR) or low risk prostate adenocarcinoma, and gland volume <80 cc. All underwent radiopaque hydrogel spacer and fiducial marker placement before simulation (computed tomography and 3-tesla T2 MRI). The clinical target volume included the entire prostate, and in FIR patients, 1-2 cm of seminal vesicle. A 2-mm expansion was applied for planning target volume (PTV), and a dose of 27 Gy was prescribed to the PTV-prostate, 23 Gy to the PTV-seminal vesicle, with an optional 30 Gy simultaneous boost to an MRI-defined dominant lesion. Primary endpoint was 3-month patient-reported changes in quality of life based on the Expanded Prostate Cancer Index Composite-26, International Prostate Symptom Score, and Sexual Health Inventory for Men questionnaires. Secondary endpoints were 6-month quality of life, acute toxicity (using Common Terminology Criteria for Adverse Events version 5.0) and early Prostate specific antigen (PSA) response.

Among the 20 patients in the phase-I cohort, 95% had FIR disease, and 50% received a simultaneous boost. At median follow-up of 8 months, a 3-month minimally clinically important change occurred in 1/20 (5%), 6/20 (30%), 2/20 (10%), 4/20 (20%), and 5/20 (25%) in urinary incontinence, urinary obstructive, bowel, sexual, and hormonal domains. There was a mean increase of 1 ± 5.4 in International Prostate Symptom Score and decrease of 1.8 ± 6.5 in Sexual Health Inventory for Men scores. Rates of grade 2 urinary and bowel toxicity were 10% and 0%, respectively, with no grade ≥3 toxicities. Mean PSA decrease at last follow-up was 70.4% ± 17.7%.

This generalizable protocol of 2-fraction prostate SABR using peri-rectal spacing is a safe approach for ultra-hypofractionated dose-escalation, with minimal acute toxicity. Longer-term outcomes and direct comparison with standard 5-fraction SABR are being studied in the phase-III randomized portion of SABR-Dual.

Cognitive fusion MRI-guided targeted biopsy (cTB) has been widely used in the diagnosis of prostate cancer (PCa). However, cTB relies heavily on the operator's experience and confidence in MRI readings. Our objective was to compare the cancer detection rates of MRI artificial intelligence-guided cTB (AI-cTB) and routine cTB and explore the added value of using AI for the guidance of cTB.

This was a prospective, single-institution randomized controlled trial (RCT) comparing clinically significant PCa (csPCa) and PCa detection rates between AI-cTB and cTB. A total of 380 eligible patients were randomized to the AI-cTB group (n = 191) or the cTB group (n = 189). The AI-cTB group underwent AI-cTB plus systematic biopsy (SB) and the cTB group underwent routine cTB plus SB. The primary outcome was the detection rate of csPCa. The reference standard was the pathological results of the combination of TB (AI-cTB/cTB) and SB. Comparisons of detection rates of csPCa and PCa between groups were performed using the chi-square test or Fisher's exact test.

The overall csPCa and PCa detection rates of the whole inclusion cohort were 58.8% and 61.3%, respectively. The csPCa detection rates of TB combined with SB in the AI-cTB group were significantly greater than those in the cTB group at both the patient level (58.64% vs. 46.56%, p = 0.018) and per-lesion level (61.47% vs. 47.79%, p = 0.004). Compared with cTB, the AI-cTB could detect a greater proportion of patients with csPCa at both the per-patient level (69.39% vs. 49.71%, p < 0.001) and per-lesion level (68.97% vs. 48.57%, p < 0.001). Multivariate logistic analysis indicated that compared with the cTB, the AI-cTB significantly improved the possibility of detecting csPCa (p < 0.001).

AI-cTB effectively improved the csPCa detection rate. This study successfully integrated AI with TB in the routine clinical workflow and provided a research paradigm for prospective AI-integrated clinical studies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06362291.

Multiparametric magnetic resonance imaging (mpMRI) of the prostate is used for prostate cancer diagnosis. However, mpMRI has lower sensitivity for small tumours. Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) offers increased sensitivity over conventional imaging. This study aims to determine whether the diagnostic accuracy of 18F-DCFPyL PSMA-PET/CT was superior to that of mpMRI for detecting prostate cancer (PCa) at biopsy.

Between 2020 and 2021, a prospective multicentre single-arm phase 3 imaging trial enrolled patients with clinical suspicion for PCa to have both mpMRI and PSMA-PET/CT (thorax to thigh), with reviewers blinded to the results of other imaging. Multiparametric MRI was considered positive for Prostate Imaging Reporting and Data System (PIRADS) 3-5. PSMA-PET/CT was assessed quantitatively (positive maximum standardised uptake value [SUVmax] >7) and qualitatively (five-point lexicon of certainty). Patients underwent targeted and systematic biopsy, with the technique at the discretion of the treating urologist. Clinically significant PCa (csPCa) was defined as International Society of Urological Pathology grade group (GG) ≥2. The primary outcome was the diagnostic accuracy for detecting PCa, reported as sensitivity, specificity, negative predictive value (NPV), and area under the curve (AUC) of the receiver operating curve. The secondary endpoints included a comparison of the diagnostic accuracy for detecting csPCa, assessing gains in combining PMSA-PET/CT with mpMRI to mpMRI alone. KEY FINDINGS AND LIMITATIONS: Of the 236 patients completing both mpMRI and PSMA-PET/CT, 184 (76.7%) had biopsy. Biopsy histology was benign (n = 73), GG 1 (n = 27), and GG ≥2 (n = 84). The diagnostic accuracy of mpMRI for detecting PCa (AUC 0.76; 95% confidence interval [CI] 0.69, 0.82) was higher than that of PSMA-PET/CT (AUC 0.63; 95% CI 0.56, 0.70, p = 0.03). The diagnostic accuracy of mpMRI for detecting csPCa (AUC 0.72; 95% CI 0.67, 0.78) was higher than that of PSMA-PET/CT (AUC 0.62; 95% CI 0.55, 0.69) but not statistically significant (p = 0.27). A combination of PSMA-PET/CT and mpMRI showed excellent sensitivity (98.8%, 95% CI 93.5%, 100%) and NPV (96%, 95% CI 79.6%, 99.9%) over mpMRI alone (86.9% and 80.7%, respectively, p = 0.01). Thirty-two patients (13.6%) had metastatic disease. They tended to be older (68.4 vs 65.1 yr, p = 0.023), and have higher prostate-specific antigen (PSA; median PSA 9.6 vs 6.2ng/ml, p < 0.001) and abnormal prostate on digital rectal examination (78.2% vs 44.1%, p < 0.001). CONCLUSIONS AND CLINICAL

Multiparametric MRI had superior diagnostic accuracy to PSMA-PET/CT for detecting PCa, though the difference is not significant in case of csPCa detection. A combination of mpMRI and PSMA-PET/CT showed improved sensitivity and NPV. PSMA-PET/CT could be considered for diagnostic use in patients unable to have mpMRI or those with concerning clinical features but negative mpMRI. PATIENT SUMMARY: In this trial, we compared the ability of 18F-labelled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) with that of multiparametric magnetic resonance imaging (mpMRI) to diagnose prostate cancer by biopsy in a prostate-specific antigen screening population. We found that MRI was superior to PSMA to diagnose prostate cancer, though there was no difference in ability to diagnose clinically significant prostate cancer. PSMA-PET/CT could be considered for diagnostic use in patients unable to have mpMRI or those with concerning clinical features but negative mpMRI. Combining MRI with PSMA-PET increases the negative predictive value over MRI alone and may help men avoid invasive prostate biopsy.

Recent guidelines favor transperineal (TP) prostate biopsies over the transrectal (TR) approach due to a reduced sepsis risk. Yet, evidence from controlled trial comparing both approaches within the MRI-targeted pathway for significant prostate cancer (PCa) detection is lacking.

To compare the significant PCa detection rate between magnetic resonance imaging (MRI)-targeted TR and TP approaches in biopsy-naïve patients. DESIGN, SETTING, AND

In this noninferiority controlled trial, we randomized (ratio 1:1) 270 MRI-positive biopsy-naïve patients. INTERVENTION: MRI-targeted TP versus TR biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: The primary outcome was the detection rate of significant PCa (International Society of Urological Pathology [ISUP] ≥2) in MRI-targeted biopsies. Secondary outcomes were any-grade PCa detection, detection on concomitant systematic biopsy, complications, and functional outcomes. RESULTS AND LIMITATIONS: Targeted biopsies identified significant PCa in 47.2% of TP and 54.2% of TR participants (-7%, p = 0.6235). On a per-lesion analysis, posterior lesions yielded higher detection rates via TR (59.0% vs 44.3%, p = 0.0443), while anterior lesions were more frequently detected via TP (40.6% vs 26.5%, p = 0.2228). The overall (any grade) cancer detection rate in targeted biopsies was comparable between groups: 71.3% (TP) versus 64.1% (TR; p = 0.2209) with significantly more ISUP 1 cases detected in the TP arm. Adverse events of grade ≥2 were not different between TP (35.7%) and TR (40.5%, p = 0.4256). One TR patient (0.8%) experienced grade 3 sepsis. Quality of life, and urinary and sexual function, as well as pain scores, were comparable between groups.

Despite a comparable overall detection rate for any-grade PCa, noninferiority of TP over TR for MRI-targeted biopsies for significant PCa detection was not demonstrated. However, MRI lesion location influenced biopsy route performance, suggesting that a pragmatic approach based on lesion location might enhance significant PCa assessment. PATIENT SUMMARY: This trial compared the efficacy and safety of two biopsy approaches for prostate cancer diagnosis. Both approaches seem complementary according to the lesion location.

Data on the efficacy and safety of screening for prostate cancer with magnetic resonance imaging (MRI) are needed from studies of follow-up screening.

In a population-based trial that started in 2015, we invited men who were 50 to 60 years of age to undergo prostate-specific antigen (PSA) screening. Men with a PSA level of 3 ng per milliliter or higher underwent MRI of the prostate. Men were randomly assigned to the systematic biopsy group, in which they underwent systematic biopsy and, if suspicious lesions were found on MRI, targeted biopsy, or the MRI-targeted biopsy group, in which they underwent MRI-targeted biopsy only. At each visit, men were invited for repeat screening 2, 4, or 8 years later, depending on the PSA level. The primary outcome was detection of clinically insignificant (International Society of Urological Pathology [ISUP] grade 1) prostate cancer; detection of clinically significant (ISUP grade ≥2) cancer was a secondary outcome, and detection of clinically advanced or high-risk (metastatic or ISUP grade 4 or 5) cancer was also assessed.

After a median follow-up of 3.9 years (approximately 26,000 person-years in each group), prostate cancer had been detected in 185 of the 6575 men (2.8%) in the MRI-targeted biopsy group and 298 of the 6578 men (4.5%) in the systematic biopsy group. The relative risk of detecting clinically insignificant cancer in the MRI-targeted biopsy group as compared with the systematic biopsy group was 0.43 (95% confidence interval [CI], 0.32 to 0.57; P<0.001) and was lower at repeat rounds of screening than in the first round (relative risk, 0.25 vs. 0.49); the relative risk of a diagnosis of clinically significant prostate cancer was 0.84 (95% CI, 0.66 to 1.07). The number of advanced or high-risk cancers detected (by screening or as interval cancer) was 15 in the MRI-targeted biopsy group and 23 in the systematic biopsy group (relative risk, 0.65; 95% CI, 0.34 to 1.24). Five severe adverse events occurred (three in the systematic biopsy group and two in the MRI-targeted biopsy group).

In this trial, omitting biopsy in patients with negative MRI results eliminated more than half of diagnoses of clinically insignificant prostate cancer, and the associated risk of having incurable cancer diagnosed at screening or as interval cancer was very low. (Funded by Karin and Christer Johansson's Foundation and others; GÖTEBORG-2 ISRCTN registry number, ISRCTN94604465.).

Dose-escalated radiation therapy is associated with better biochemical control at the expense of toxicity. Stereotactic body radiation therapy (SBRT) with dose escalation to the dominant intraprostatic lesion (DIL) provides a logical approach to improve outcomes in high-risk disease while limiting toxicity. This study evaluated the toxicity and quality of life (QoL) with CyberKnife-based SBRT and simultaneous integrated boost in localized prostate cancer. METHODS AND MATERIALS: Eligible participants included newly diagnosed, biopsy-proven unfavorable intermediate- to high-risk localized prostate cancer (at least 1 of the following: Gleason ≥4+3, magnetic resonance imaging(MRI)-defined T3a N0, prostate-specific antigen ≥20) with up to 2 MRI-identified DILs. Participants received 36.25 Gy in 5 fractions on alternative days with a simultaneous boost to DIL up to 47.5 Gy as allowed by organ-at-risk constraints delivered by CyberKnife. All participants received androgen deprivation therapy. The primary outcome measure was acute grade 2+ genitourinary toxicity. Acute and late genitourinary and gastrointestinal toxicity using Radiation Therapy Oncology Group scoring, biochemical parameters, International Prostate Symptom Score, International Index of Erectile Function 5, and EQ-5D QoL outcomes were assessed.

Between 2013 and 2023, 20 participants were enrolled with a median follow-up of 30 months. The median D95 dose to DIL was 47.43 Gy. Cumulative acute grade 2+ genitourinary and gastrointestinal toxicity were 25% and 30%, respectively. One patient developed acute grade 3 genitourinary toxicity (5%). There is no late grade 3 genitourinary or gastrointestinal toxicity to date. International Prostate Symptom Score and urinary QoL scores recovered to baseline by 6 months. Patient-reported outcomes showed no significant change in EQ-5D QoL scores at 12 weeks and 1 year. There are no cases of biochemical relapse reported to date.

CyberKnife SBRT-delivered dose of 36.25 Gy to the prostate with a simultaneous integrated boost up to 47.5 Gy is well tolerated. Acute and late genitourinary and gastrointestinal toxicity rates are comparable to other contemporary SBRT trials and series with focal boost.

NCT03253744 is a phase 1 trial with the primary objective to identify the maximum tolerated dose (MTD) of salvage stereotactic body radiation therapy (SBRT) in patients with local prostate cancer recurrence after brachytherapy. Additional objectives included biochemical control and imaging response. METHODS AND MATERIALS: This trial was initially designed to test 3 therapeutic dose levels (DLs): 40 Gy (DL1), 42.5 Gy (DL2), and 45 Gy (DL3) in 5 fractions. Intensity modulation was used to deliver the prescription dose to the magnetic resonance imaging and prostate-specific membrane antigen-based positron emission tomography imaging-defined gross tumor volume while simultaneously delivering 30 Gy to an elective volume defined by the prostate gland. This phase 1 trial followed a 3+3 design with a 3-patient expansion at the MTD. Toxicities were scored until trial completion at 2 years post-SBRT using Common Terminology Criteria for Adverse Events version 5.0. Escalation was halted if 2 dose limiting toxicities occurred, defined as any persistent (>4 days) grade 3 toxicity occurring within the first 3 weeks after SBRT or any grade ≥3 genitourinary (GU) or grade 4 gastrointestinal toxicity thereafter.

Between August 2018 and January 2023, 9 patients underwent salvage SBRT and were observed for a median of 22 months (Q1-Q3, 20-43 months). No grade 3 to 5 adverse events related to study treatment were observed; thus, no dose limiting toxicities occurred during the observation period. Escalation was halted by amendment given excellent biochemical control in DL1 and DL2 in the setting of a high incidence of clinically significant late grade 2 GU toxicity. Therefore, the MTD was considered 42.5 Gy in 5 fractions (DL2). One- and 2-year biochemical progression-free survival were 100% and 86%, representing a single patient in the trial cohort with biochemical failure (prostate-specific antigen [PSA] nadir + 2.0) at 20 months posttreatment.

The MTD of salvage SBRT for the treatment of intraprostatic radiorecurrence after brachytherapy was 42.5 Gy in 5 fractions producing an 86% 2-year biochemical progression-free survival rate, with 1 poststudy failure at 20 months. The most frequent clinically significant toxicity was late grade 2 GU toxicity.

Survivors of surgically managed prostate cancer may experience urinary incontinence and erectile dysfunction. Our aim was to determine if 68Ga-prostate-specific membrane antigen-11 positron emission tomography CT (PSMA-PET) in addition to multiparametric (mp) MRI scans improved surgical decision-making for nonnerve-sparing or nerve-sparing approach.

We prospectively enrolled 50 patients at risk for extraprostatic extension (EPE) who were scheduled for prostatectomy. After mpMRI and PSMA-PET images were read for EPE prediction, surgeons prospectively answered questionnaires based on mpMRI and PSMA-PET scans on the decision for nerve-sparing or nonnerve-sparing approach. Final whole-mount pathology was the reference standard. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic curves were calculated and McNemar's test was used to compare imaging modalities.

The median age and PSA were 61.5 years and 7.0 ng/dL. The sensitivity for EPE along the posterior neurovascular bundle was higher for PSMA-PET than mpMRI (86% vs 57%, P = .03). For MRI, the specificity, positive predictive value, negative predictive value, and area under the curve for the receiver operating characteristic curves were 77%, 40%, 87%, and 0.67, and for PSMA-PET were 73%, 46%, 95%, and 0.80. PSMA-PET and mpMRI reads differed on 27 nerve bundles, with PSMA-PET being correct in 20 cases and MRI being correct in 7 cases. Surgeons predicted correct nerve-sparing approach 74% of the time with PSMA-PET scan in addition to mpMRI compared to 65% with mpMRI alone (P = .01).

PSMA-PET scan was more sensitive than mpMRI for EPE along the neurovascular bundles and improved surgical decisions for nerve-sparing approach. Further study of PSMA-PET for surgical guidance is warranted in the unfavorable intermediate-risk or worse populations.

To determine the accuracy of fluorine-18 PSMA-1007 PET/computed tomography (18F-PSMA-1007 PET/CT) compared to multiparametric magnetic resonance imaging (MRI) in the primary locoregional staging of intermediate-risk and high-risk prostate cancers. DESIGN, SETTING, AND

The Next Generation Trial was a phase 2 prospective validating paired cohort study assessing the accuracy of 18F-PSMA-1007 PET/CT and MRI for locoregional staging of prostate cancer, with results of histopathologic examination as the reference standard comparator. Radiologists, nuclear medicine physicians, and pathologists were blinded to preoperative clinical, pathology, and imaging data. Patients underwent all imaging studies and radical prostatectomies at 2 tertiary care hospitals in Alberta, Canada. Eligible participants included men with intermediate-risk or high-risk prostate cancer who consented to radical prostatectomy. Participants who underwent radical prostatectomy were included in the final analysis. Patients were recruited between March 2022 and June 2023, and data analysis occurred between July 2023 and December 2023. EXPOSURES: All participants underwent both 18F-PSMA-1007 PET/CT and MRI within 2 weeks of one another and before radical prostatectomy. MAIN OUTCOMES AND MEASURES: The primary outcome was the correct identification of the prostate cancer tumor stage by each imaging test. The secondary outcomes were correct identification of the dominant nodule, laterality, extracapsular extension, and seminal vesical invasion.

Of 150 eligible men with prostate cancer, 134 patients ultimately underwent radical prostatectomy (mean [SD] age at prostatectomy, 62.0 [5.7] years). PSMA PET was superior to MRI for the accurate identification of the final pathological tumor stage (61 [45%] vs 38 [28%]; P = .003). PSMA PET was also superior to MRI for the correct identification of the dominant nodule (126 [94%] vs 112 [83%]; P = .01), laterality (86 [64%] vs 60 [44%]; P = .001), and extracapsular extension (100 [75%] vs 84 [63%]; P = .01), but not for seminal vesicle invasion (122 [91%] vs 115 [85%]; P = .07). CONCLUSIONS AND RELEVANCE: In this phase 2 prospective validating paired cohort study, 18F-PSMA-1007 PET/CT was superior to MRI for the locoregional staging of prostate cancer. These findings support PSMA PET in the preoperative workflow of intermediate-risk and high-risk tumors.

Magnetic resonance imaging(MRI) and targeted biopsies reduce overdiagnosis of prostate cancer(PC). It is uncertain how this strategy performs for low PSA levels. The objective was to investigate the PI-RADS distribution, frequency and characteristics of screen-detected PC with PSA of 1.8-<3ng/ml and 3-<10ng/ml.

In the population-based Göteborg-2 screening study, 17 974 men choose to participate by having a PSA(2015-2020). One-third of the participants(n=6006) were randomized to Arm 3, men with a PSA ≥1.8ng/ml were recommended MRI. Men with positive MRI(PI-RADS3-5) had four targeted biopsies from each MRI-visible lesion. Clinically significant PC was defined as Gleason score ≥3+4. KEY FINDINGS AND LIMITATIONS: 6006 men were included. Median age was 55.9 years. 670(11%) had PSA of 1.8-<3ng/ml(low-PSA group), median PSA 2.1ng/ml, and 377(6.3%) had PSA of 3-<10ng/ml(high-PSA group), median PSA 3.9ng/ml. PI-RADS scores of 3, 4, and 5 were observed in 7.8%, 15%, and 1.0% in the low-PSA group, and in 6.9%, 17%, and 5.3% in the high-PSA group, respectively. PC was found in 64 men (41%, 95%CI 0.33-0.49) with positive MRI findings in the low-PSA group, 33(21%) had Gleason 6 and 31(20%) had Gleason ≥7. In the high-PSA group, PC was detected in 61men (56%, 95%CI 0.46-0.66), 26(24%) had Gleason 6 and 35(32%) had Gleason ≥7. Limitations include results from only a single screening round. CONCLUSIONS AND CLINICAL

A non-negligible number of men with PSA 1.8-3ng/ml have clinically significant PC. Whether a delay in the diagnosis of these tumors until they reached PSA ≥3ng/ml would impair their chance of cure remains to be evaluated.

This study aimed to verify the feasibility and short-term prognosis of prostatectomy without biopsy.

Patients with a rising PSA level ranging from 4 to 30 ng/mL were scheduled for multiparametric (mp) MRI and 18F-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Forty-seven patients (cT2N0M0) with Prostate Imaging Reporting and Data System ≥ 4 and molecular imaging PSMA score ≥ 2 were enrolled. All candidates underwent robot-assisted laparoscopic radical prostatectomy without biopsy. Prostate cancer detection rate, index tumors localization correspondence rate, positive surgical margin, complications, postoperative hospital stay, and PSA level in a 6-week postoperative follow-up visit were collected.

All the patients with positive mpMRI and PSMA PET were diagnosed with clinically significant prostate cancer. A total of 80 lesions were verified as cancer by pathology, of which 63 cancer lesions were clinically significant prostate cancer. Fifty-one lesions were simultaneously found by mpMRI and PSMA PET. A total of 23 lesions were invisible on either image, and all lesions were ≤ International Society of Urological Pathology 2 or ≤ 15 mm. Forty-five (95.7%) index tumors found by mpMRI combined with PSMA PET were consistent with pathology. Nine patients reported positive surgical margin.

Biopsy-free prostatectomy is safe and feasible for patients with evaluation strictly by mpMRI combined with 18F-PSMA PET/CT.

To assess histopathological outcomes, as well as feasibility and safety of targeted microwave ablation (TMA) via the Trinity® system (KOELIS, La Tronche, France). PATIENTS AND

Prospective, single-institution, interventional Phase IIa study with an 'ablate-and-resect' design. In all, 11 patients diagnosed with localised prostate cancer (PCa) underwent TMA via the Trinity system under conscious sedation in an outpatient setting using a single transrectal TATO® 18-G antenna with different treatment regimens. Magnetic resonance imaging (MRI) and robot-assisted radical prostatectomy (RARP) were conducted at 7 days and 1 month after TMA, respectively. Nine patients received RARP, and two patients chose to withdraw their consent following TMA. These men chose an active surveillance protocol upon confirmation of a low-risk prostate cancer diagnosis. Functional outcomes and adverse events were evaluated at baseline and follow-up visits using validated questionnaires. Prostate volumetry and confirmation of necrosis were carried out through MRI and whole-mount histopathological examination.

The TMA was successfully executed, and all patients were discharged on the same day. No severe adverse events (Common Terminology Criteria for Adverse Events Grade ≥3) were reported at the 7-day and 1-month follow-up visits. Additionally, no declines were observed in urinary, sexual and ejaculation functional outcomes. T1-weighted MRI revealed clear and well-defined ablation zones. The RARP was executed without difficulty, particularly during the dissection of the posterior plane. As a result, no intraoperative complications were encountered. Histopathological assessment on surgical specimens confirmed the absence of viable cells, indicating complete necrosis of the ablative zone if a power intensity >10 W was used during TMA. Ablation zone volumetry revealed no notable distinctions between the three-dimensional segmentation of the virtual ablation zone at TMA (median volume: 2 mL) and MRI (median volume: 1.923 mL). Conversely, a significant reduction was noted in the surgical specimen (median volume: 0.221 mL).

Targeted microwave ablation via the Trinity system for localised PCa treatment proves to be a secure and feasible procedure, with complete necrosis evidence within the ablation zone on surgical specimens.

Artificial intelligence (AI) systems can potentially aid the diagnostic pathway of prostate cancer by alleviating the increasing workload, preventing overdiagnosis, and reducing the dependence on experienced radiologists. We aimed to investigate the performance of AI systems at detecting clinically significant prostate cancer on MRI in comparison with radiologists using the Prostate Imaging-Reporting and Data System version 2.1 (PI-RADS 2.1) and the standard of care in multidisciplinary routine practice at scale.

In this international, paired, non-inferiority, confirmatory study, we trained and externally validated an AI system (developed within an international consortium) for detecting Gleason grade group 2 or greater cancers using a retrospective cohort of 10 207 MRI examinations from 9129 patients. Of these examinations, 9207 cases from three centres (11 sites) based in the Netherlands were used for training and tuning, and 1000 cases from four centres (12 sites) based in the Netherlands and Norway were used for testing. In parallel, we facilitated a multireader, multicase observer study with 62 radiologists (45 centres in 20 countries; median 7 [IQR 5-10] years of experience in reading prostate MRI) using PI-RADS (2.1) on 400 paired MRI examinations from the testing cohort. Primary endpoints were the sensitivity, specificity, and the area under the receiver operating characteristic curve (AUROC) of the AI system in comparison with that of all readers using PI-RADS (2.1) and in comparison with that of the historical radiology readings made during multidisciplinary routine practice (ie, the standard of care with the aid of patient history and peer consultation). Histopathology and at least 3 years (median 5 [IQR 4-6] years) of follow-up were used to establish the reference standard. The statistical analysis plan was prespecified with a primary hypothesis of non-inferiority (considering a margin of 0·05) and a secondary hypothesis of superiority towards the AI system, if non-inferiority was confirmed. This study was registered at ClinicalTrials.gov, NCT05489341.

Of the 10 207 examinations included from Jan 1, 2012, through Dec 31, 2021, 2440 cases had histologically confirmed Gleason grade group 2 or greater prostate cancer. In the subset of 400 testing cases in which the AI system was compared with the radiologists participating in the reader study, the AI system showed a statistically superior and non-inferior AUROC of 0·91 (95% CI 0·87-0·94; p<0·0001), in comparison to the pool of 62 radiologists with an AUROC of 0·86 (0·83-0·89), with a lower boundary of the two-sided 95% Wald CI for the difference in AUROC of 0·02. At the mean PI-RADS 3 or greater operating point of all readers, the AI system detected 6·8% more cases with Gleason grade group 2 or greater cancers at the same specificity (57·7%, 95% CI 51·6-63·3), or 50·4% fewer false-positive results and 20·0% fewer cases with Gleason grade group 1 cancers at the same sensitivity (89·4%, 95% CI 85·3-92·9). In all 1000 testing cases where the AI system was compared with the radiology readings made during multidisciplinary practice, non-inferiority was not confirmed, as the AI system showed lower specificity (68·9% [95% CI 65·3-72·4] vs 69·0% [65·5-72·5]) at the same sensitivity (96·1%, 94·0-98·2) as the PI-RADS 3 or greater operating point. The lower boundary of the two-sided 95% Wald CI for the difference in specificity (-0·04) was greater than the non-inferiority margin (-0·05) and a p value below the significance threshold was reached (p<0·001).

An AI system was superior to radiologists using PI-RADS (2.1), on average, at detecting clinically significant prostate cancer and comparable to the standard of care. Such a system shows the potential to be a supportive tool within a primary diagnostic setting, with several associated benefits for patients and radiologists. Prospective validation is needed to test clinical applicability of this system. FUNDING: Health~Holland and EU Horizon 2020.

The comparative effectiveness of transrectal and transperineal prostate biopsy in detecting clinically significant prostate cancer is not well understood. We conducted a randomized clinical trial to determine whether transperineal biopsy improves the detection of clinically significant prostate cancer.

Of the 840 men randomized, 93% were White, 44% had a previous biopsy, with a median age of 66 years and median PSA density of 0.14. Of these, 384 underwent transrectal and 398 underwent transperineal prostate biopsy. Prebiopsy prostate MRI was performed in 96% of men. Grade Group ≥ 2 prostate cancer was classified as clinically significant. Odds ratios were calculated using logistic regression to evaluate the effect of biopsy procedures on cancer detection rates.

The detection rates of clinically significant prostate cancer were 47.1% and 43.2% (odds ratio 1.17; 95% CI, 0.88-1.55) for transrectal and transperineal biopsy, respectively. Age, PSA density, clinical stage and Prostate Imaging Reporting and Data System score were associated with the diagnosis of clinically significant cancer, whereas history of previous biopsy, anterior tumors, and biopsy procedure (transrectal or transperineal) were not. Clinically significant cancer detection rates in biopsy-naïve men undergoing MRI-targeted transrectal or transperineal biopsy were 59% and 62%, respectively. The overall cancer detection rates following transrectal and transperineal biopsy were 72.1% and 70.4%, respectively.

There was no significant difference noted in the detection of clinically significant prostate cancer following transrectal or transperineal prostate biopsy. Urologists may utilize either biopsy procedure that best suits their patients' needs and practice setting.

The prospective randomized PRECISE trial demonstrated that magnetic resonance imaging (MRI) with only targeted biopsy (TBx) was noninferior to systematic transrectal ultrasound biopsy (SBx) in the detection of International Society of Urological Pathology grade group (GG) ≥2 prostate cancer (PC). An unanswered question is the outcome for patients who avoided a biopsy because of negative MRI findings.

To explore the rate of PC diagnosis based on 2-yr MRI for PRECISE participants who had no biopsy and for patients who had a negative result or GG 1 on TBx in comparison to those with a negative result or GG 1 on SBx. DESIGN, SETTING, AND

The PRECISE prospective trial was conducted at five Canadian academic centers. The present analysis was for trial participants who were not diagnosed with clinically significant PC (csPC) at baseline. Of 453 randomized patients, 146 were diagnosed with GG ≥2 at baseline and were excluded. Eligible patients for this study included 83 men from the MRI arm who had negative MRI findings and no biopsy, 120 from the overall cohort who had a negative SBx or TBx, and 72 from the overall cohort who were diagnosed with GG 1 disease. INTERVENTION: MRI at 2 yr in all men in the MRI and SBx arms and TBx for lesions with a Prostate Imaging-Reporting and Data System score of ≥3 or on the basis of clinical suspicion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the proportion of men diagnosed with GG ≥2 cancer. Secondary outcomes included the MRI outcome and the proportion of men diagnosed with GG 1 PC. RESULTS AND LIMITATIONS: Evaluable 2-yr MRI scans were available for 75 (56%) eligible patients in the MRI arm and 69 (49%) in the SBx arm. Of these patients, 55 (73%) in the MRI arm and 51 (67%) SBx arm had negative 2-yr MRI. Of the 76 patients in the SBx arm with 2-yr MRI, 16 (21%) had a biopsy, for which the result was negative in eight (10%), GG1 in two (2.6%), and GG ≥2 in six (7.9%) cases. Of the 75 men in the MRI arm with 2-yr MRI, eight (11%) were biopsied, for which the result was negative in four cases (5%) and GG ≥2 in the other four (5%). At 2 yr, including baseline biopsy results, 116/221 (52.5%) in the MRI arm and 113/204 (55%) in the SBx arm were free of GG ≥2 disease, treatment, death from any cause, or progression (OR 1.08; p = 0.66).

After 2-yr follow-up including MRI for patients in both arms of PRECISE, there was no difference in the rate of csPC diagnosis between the MRI and SBx groups, even though 38% of men in the MRI group avoided an initial biopsy. PATIENT SUMMARY: The PRECISE trial compared systematic biopsy of the prostate to a strategy of magnetic resonance imaging (MRI) with targeted biopsy of any lesions suspicious for cancer on the scan. After 2 years of follow-up that included 2-year MRI with or without biopsy in both groups, there was no difference in the rate of diagnosis of significant cancer, even though 38% of men in the initial MRI arm avoided an initial biopsy, and 30% avoided biopsy altogether. The PRECISE trial is registered on ClinicalTrials.gov as NCT02936258.

A prerequisite before introducing a screening program is that the screening examinations are acceptable to participants.

To evaluate the acceptance and bother of prostate cancer screening examinations. DESIGN, SETTING, AND

The randomized population-based GÖTEBORG-2 prostate cancer screening trial invited >37 000 men for prostate-specific antigen (PSA) testing followed by magnetic resonance imaging (MRI) in case of elevated PSA and prostate biopsy (targeted and/or systematic) if indicated. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Participants were asked to fill out a questionnaire and rate the level of bother associated with each examination (PSA, MRI, and prostate biopsy) on a categorical scale ranging from 1 to 5 (1 = "not at all bothersome" and 5 = "very bothersome"), and to rate their willingness to repeat the examinations, by marking an X on a continuous scale ranging from 0 to 10 (0 = "yes, without any hesitation" and 10 = "no, absolutely not"). Wilcoxon signed rank test was used. RESULTS AND LIMITATIONS: Compliance with MRI was 96% (1790/1872), compliance with biopsy was 89% (810/907), and the response rate to the questionnaire was 75% (608/810). Men who underwent all examinations (n = 577) responded that biopsy was more bothersome than PSA test (p < 0.001) and MRI (p < 0.001). High levels of bother (≥4 out of 5) were reported by 2% (12/577) for PSA test, 8% (46/577) for MRI, and 43% (247/577) for biopsy. Men were more willing to repeat MRI than biopsy (p < 0.001), but the difference was small (median 0.2 [interquartile range 0.1-0.6] vs 0.5 [0.1-2.0]).

Biopsies are more bothersome than MRI, but a large majority of men accept to repeat both examinations if necessary. Omitting biopsy for MRI-negative men and shifting to targeted biopsies only will reduce bother for men participating in prostate cancer screening. PATIENT SUMMARY: We asked men how bothersome they found the prostate-specific antigen (PSA) test, magnetic resonance imaging (MRI), and prostate biopsies. Biopsies were more bothersome than PSA and MRI, but most men were willing to repeat all procedures if necessary.

We prospectively enrolled 27 men with suspected biochemically recurrent PC after initial treatment but noncontributory conventional imaging results (negative or equivocal findings on MRI, CT, and/or bone scan). Participants underwent 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI within 2 wk in noncontrolled order. The SUVmax of putative PC lesions was measured and compared with a composite reference standard (histopathology, follow-up imaging, prostate-specific antigen change). The SUVmax and SUVmean of background organs were measured. Vital signs were recorded before injection of the radiopharmaceuticals and after the scans. Adverse events were recorded up to 72 h after each scan.

The prostate-specific antigen level at enrollment was 3.5 ± 3.9 ng/mL (range, 0.3-13.5 ng/mL). 68Ga-NeoB PET/MRI detected 31 lesions in 18 patients (66.7%), whereas 68Ga-PSMA-R2 identified 20 lesions in 15 participants (55.6%). 68Ga-NeoB PET/MRI showed higher sensitivity (85.7% vs. 71.4%), accuracy (88.9% vs. 77.8%), and negative predictive value (66.7% vs. 50.0%) than 68Ga-PSMA-R2, whereas specificity and positive predictive value were equally high (100.0% for both). In 6 patients, 68Ga-NeoB PET/MRI identified 14 lesions that were false-negative on 68Ga-PSMA-R2 PET/MRI. The mean lesion SUVmax was 6.6 ± 3.2 (range, 2.9-13.2) for 68Ga-NeoB and 4.4 ± 1.5 (range, 2.6-8.8) for 68Ga-PSMA-R2 (P = 0.019). Overall lower uptake was noted in tumors and background organs for 68Ga-PSMA-R2. There were no significant changes in vital signs before and after the scans. No adverse events were reported in the 72-h period after scans.

68Ga-NeoB and 68Ga-PSMA-R2 are safe for diagnostic imaging. 68Ga-NeoB PET/MRI showed better diagnostic performance than 68Ga-PSMA-R2. 68Ga-PSMA-R2 showed overall lower uptake, equally in background organs and tumors, and might therefore not be an ideal theranostic compound. Further evaluation in larger cohorts is needed to confirm our preliminary data.

To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan. DESIGN, SETTING, AND

The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020. INTERVENTIONS: Participating men randomized to the intervention underwent PSA testing. Those with a PSA level of 3.0 ng/mL or higher underwent additional testing for high-grade prostate cancer with a 4-kallikrein panel risk score. Those with a kallikrein panel score of 7.5% or higher underwent an MRI of the prostate gland, followed by targeted biopsies for those with abnormal prostate gland MRI findings. Final data collection occurred through June 31, 2023. MAIN OUTCOMES AND MEASURES: In descriptive exploratory analyses, the cumulative incidence of low-grade and high-grade prostate cancer after the first screening round were compared between the group invited to undergo prostate cancer screening and the control group.

Of 60 745 eligible men (mean [SD] age, 57.2 [4.0] years), 15 201 were randomized to be invited and 45 544 were randomized not to be invited to undergo prostate cancer screening. Of 15 201 eligible males invited to undergo screening, 7744 (51%) participated. Among them, 32 low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected, with 1 cancer grade group result missing. Among the 7457 invited men (49%) who refused participation, 7 low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%) were detected, with 7 cancer grade groups missing. For the entire invited screening group, 39 low-grade prostate cancers (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected. During a median follow-up of 3.2 years, in the group not invited to undergo screening, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected. The risk difference for the entire group randomized to the screening invitation vs the control group was 0.11% (95% CI, 0.03%-0.20%) for low-grade and 0.51% (95% CI, 0.33%-0.70%) for high-grade cancer. CONCLUSIONS AND RELEVANCE: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality outcome. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03423303.

National Comprehensive Cancer Network guidelines include prostate-specific membrane antigen (PSMA)-targeted PET for detection of biochemical recurrence of prostate cancer. However, targeting a single tumour characteristic might not be sufficient to reflect the full extent of disease. Gastrin releasing peptide receptors (GRPR) have been shown to be overexpressed in prostate cancer. In this study, we aimed to evaluate the diagnostic performance of the GRPR-targeting radiopharmaceutical 68Ga-RM2 in patients with biochemical recurrence of prostate cancer.

This single-centre, single-arm, phase 2/3 trial was done at Stanford University (USA). Adult patients (aged ≥18 years) with biochemical recurrence of prostate cancer, a Karnofsky performance status of 50 or higher, increasing prostate-specific antigen concentration 0·2 ng/mL or more after prostatectomy or 2 ng/mL or more above nadir after radiotherapy, and non-contributory conventional imaging (negative CT or MRI, and bone scan) were eligible. All participants underwent 68Ga-RM2 PET-MRI. The primary outcome was the proportion of patients with PET-positive findings on 68Ga-RM2 PET-MRI compared with MRI alone after initial therapy, at a per-patient and per-lesion level. The primary outcome would be considered met if at least 30% of patients had one or more lesions detected by 68Ga-RM2 PET-MRI and the detection by 68Ga-RM2 PET-MRI was significantly greater than for MRI. Each PET scan was interpreted by three independent masked readers using a standardised evaluation criteria. This study is registered with ClinicalTrials.gov, NCT02624518, and is complete.

Between Dec 12, 2015, and July 27, 2021, 209 men were screened for eligibility, of whom 100 were included in analyses. Median follow-up was 49·3 months (IQR 36·7-59·2). The primary endpoint was met; 68Ga-RM2 PET-MRI was positive in 69 (69%) patients and MRI alone was positive in 40 (40%) patients (p<0·0001). In the per-lesion analysis 68Ga-RM2 PET-MRI showed significantly higher detection rates than MRI alone (143 vs 96 lesions; p<0·0001). No grade 1 or worse events were reported.

68Ga-RM2 PET-MRI showed better diagnostic performance than MRI alone in patients with biochemical recurrence of prostate cancer. Further prospective comparative studies with PSMA-targeted PET are needed to gain a better understanding of GRPR and PSMA expression patterns in these patients. FUNDING: The US Department of Defense.

To evaluate biomarker-based risk estimation (Stockholm3 risk scores or prostate-specific antigen [PSA] levels) with systematic biopsies vs an MRI-enhanced strategy (PSA levels and MRI with systematic and targeted biopsy) for the detection of clinically significant prostate cancer in a screening setting. DESIGN, SETTING, AND

This open-label randomized clinical trial conducted in Stockholm, Sweden, between April 4, 2018, and December 10, 2020, recruited men aged 50 to 74 years with no history of prostate cancer. Participants underwent blood sampling for PSA and Stockholm3 tests to estimate their risk of clinically significant prostate cancer (Gleason score ≥3 + 4). After the blood tests were performed, participants were randomly assigned in a 2:3 ratio to receive a Stockholm3 test with systematic biopsy (biomarker group) or a PSA test followed by MRI with systematic and targeted biopsy (MRI-enhanced group). Data were analyzed from September 1 to November 5, 2023. INTERVENTIONS: In the biomarker group, men with a Stockholm3 risk score of 0.15 or higher underwent systematic biopsies. In the MRI-enhanced group, men with a PSA level of 3 ng/mL or higher had an MRI and those with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3 or higher (range: 1-5, with higher scores indicating a higher likelihood of clinically significant prostate cancer) underwent targeted and systematic biopsies. MAIN OUTCOMES AND MEASURES: Primary outcome was detection of clinically significant prostate cancer (Gleason score ≥3 + 4). Secondary outcomes included detection of clinically insignificant cancer (Gleason score ≤6) and the number of biopsy procedures performed.

Of 12 743 male participants (median [IQR] age, 61 [55-67] years), 5134 were assigned to the biomarker group and 7609 to the MRI-enhanced group. In the biomarker group, 8.0% of men (413) had Stockholm3 risk scores of 0.15 or higher and were referred for systematic biopsies. In the MRI-enhanced group, 12.2% of men (929) had a PSA level of 3 ng/mL or higher and were referred for MRI with biopsies if they had a PI-RADS score of 3 or higher. Detection rates of clinically significant prostate cancer were comparable between the 2 groups: 2.3% in the biomarker group and 2.5% in the MRI-enhanced group (relative proportion, 0.92; 95% CI, 0.73-1.15). More biopsies were performed in the biomarker group than in the MRI-enhanced group (326 of 5134 [6.3%] vs 338 of 7609 [4.4%]; relative proportion, 1.43 [95% CI, 1.23-1.66]), and more indolent prostate cancers were detected (61 [1.2%] vs 41 [0.5%]; relative proportion, 2.21 [95% CI, 1.49-3.27]). CONCLUSIONS AND RELEVANCE: Findings of this randomized clinical trial indicate that combining a Stockholm3 test with systematic biopsies is comparable with MRI-based screening with PSA levels and systematic and targeted biopsies for detection of clinically significant prostate cancer, but this approach resulted in more biopsies as well as detection of a greater number of indolent cancers. In regions where access to MRI is lacking, the Stockholm3 test can aid in selecting patients for systematic prostate biopsy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03377881.

Real-time intrafraction tracking/gating is an integral component of magnetic resonance imaging-guided radiation therapy (MRgRT) and may have contributed to the acute toxicity reduction during prostate stereotactic body radiation therapy observed on the MRgRT-arm of the MIRAGE (MAGNETIC RESONANCE IMAGING-GUIDED Stereotactic Body Radiotherapy for Prostate Cancer) randomized trial (NCT04384770). Herein we characterized intrafraction prostate motion and assessed gating effectiveness. METHODS AND MATERIALS: Seventy-nine patients were treated on an MR-LINAC. Real-time cine imaging was acquired at 4Hz in a sagittal plane. If >10% of the prostate area moved outside of a 3-mm gating boundary, an automatic beam hold was initiated. An in-house tool was developed to retrospectively extract gating signal for all patients and identify the tracked prostate in each cine frame for a subgroup of 40 patients. The fraction of time the prostate was within the gating window was defined as the gating duty cycle (GDC).

A total of 391 treatments from 79 patients were analyzed. Median GDC was 0.974 (IQR, 0.916-0.983). Fifty (63.2%) and 24 (30.4%) patients had at least 1 fraction with GDC ≤0.9 and GDC ≤0.8, respectively. Incidence of low GDC fractions among patients appeared stochastic. Patients with minimum GDC <0.8 trended toward more frequent grade 2 genitourinary toxicity compared with those with minimum GDC >0.8 (38% vs 18%, P = .065). Prostate intrafraction motion was mostly along the bladder-rectum axis and predominantly in the superior-anterior direction. Motion in the inferior-posterior direction was associated with significantly higher rate of acute grade 2 genitourinary toxicity (66.7% vs 13.9%, P = .001). Gating limited mean prostate motion during treatment delivery in fractions with a GDC <0.9 (<0.8) to 2.9 mm (2.9 mm) versus 4.1 mm (4.7 mm) for ungated motion.

Fractions with large intrafraction motion were associated with increased toxicity and their occurrence among patients appears stochastic. Real-time tracking/gating effectively mitigated this motion and is likely a major contributing factor of acute toxicity reduction associated with MRgRT.

To demonstrate the added benefit of multiparametric (mp)MRI risk stratification during active surveillance.

This prospective, single-arm, nonrandomized study included 82 men with low-risk prostate cancer (PCa). We compared two biopsy strategies in parallel. The first biopsy strategy was an in-bore and transrectal ultrasound (TRUS) biopsy in men with suspicious mpMRI findings. The second was a TRUS biopsy in all 82 men, blinded to the results of the previously performed mpMRI.

We identified 27/82 men with suspicious mpMRI. Of those 27 men, we detected 8/27 with csPCa on biopsy, and we identified two men with in-bore biopsy exclusively, three men with TRUS biopsy exclusively, and three men with both biopsy strategies. Of the 55/82 men with nonsuspicious mpMRI (who only received TRUS biopsies), two men had csPCa. TRUS biopsy of the entire cohort of 82 men would have led to the correct diagnosis of 80% men with csPCa, requiring all 82 men to receive biopsies (csPCa in 10% of the 82 biopsies). Conducting in-bore biopsies plus TRUS biopsies in men with suspicious mpMRI would have also led to the detection of 80% of men with csPCa, requiring only 27 men to receive biopsies (csPCa in 30% of the 27 biopsies).

The combination of TRUS and in-bore biopsies, limited to men with suspicious mpMRI, resulted in a similar detection rate of csPCa compared to TRUS biopsies of all men but required only one-third of men to undergo biopsy. Our results indicate that in-bore and TRUS biopsies continue to complement each other.

Bone metastasis is a significant contributor to morbidity and mortality in advanced prostate cancer, and early diagnosis is challenging due to its insidious onset. The use of machine learning to obtain prognostic information from pathological images has been highlighted. However, there is a limited understanding of the potential of early prediction of bone metastasis through the feature combination method from various sources. This study presents a method of integrating multimodal data to enhance the feasibility of early diagnosis of bone metastasis in prostate cancer. METHODS AND MATERIALS: Overall, 211 patients diagnosed with prostate cancer (PCa) at Gansu Provincial Hospital between January 2017 and February 2023 were included in this study. The patients were randomized (8:2) into a training group (n = 169) and a validation group (n = 42). The region of interest (ROI) were segmented from the three magnetic resonance imaging (MRI) sequences (T2WI, DWI, and ADC), and pathological features were extracted from tissue sections (hematoxylin and eosin [H&E] staining, 10 × 20). A deep learning (DL) model using ResNet 50 was employed to extract deep transfer learning (DTL) features. The least absolute shrinkage and selection operator (LASSO) regression method was utilized for feature selection, feature construction, and reducing feature dimensions. Different machine learning classifiers were used to build predictive models. The performance of the models was evaluated using receiver operating characteristic curves. The net clinical benefit was assessed using decision curve analysis (DCA). The goodness of fit was evaluated using calibration curves. A joint model nomogram was eventually developed by combining clinically independent risk factors.

The best prediction models based on DTL and pathomics features showed area under the curve (AUC) values of 0.89 (95% confidence interval [CI], 0.799-0.989) and 0.85 (95% CI, 0.714-0.989), respectively. The AUC for the best prediction model based on radiomics features and combining radiomics features, DTL features, and pathomics features were 0.86 (95% CI, 0.735-0.979) and 0.93 (95% CI, 0.854-1.000), respectively. Based on DCA and calibration curves, the model demonstrated good net clinical benefit and fit.

Multimodal radiomics and pathomics serve as valuable predictors of the risk of bone metastases in patients with primary PCa.

To compare the diagnostic accuracy and detection rates of PET/MRI with [68Ga]Ga-PSMA-11 and [68Ga]Ga-M2 in patients with biochemical recurrence of prostate cancer (PCa).

Sixty patients were enrolled in this prospective single-center phase II clinical trial from June 2020 to October 2022. Forty-four/60 completed all study examinations and were available at follow-up (median: 22.8 months, range: 6-31.5 months). Two nuclear medicine physicians analyzed PET images and two radiologists interpreted MRI; images were then re-examined to produce an integrated PET/MRI report for both [68Ga]Ga-PSMA-11 and [68Ga]Ga-RM2 examinations. A composite reference standard including histological specimens, response to treatment, and conventional imaging gathered during follow-up was used to validate imaging findings. Detection rates, accuracy, sensitivity, specificity, positive, and negative predictive value were assessed. McNemar's test was used to compare sensitivity and specificity on a per-patient base and detection rate on a per-region base. Prostate bed, locoregional lymph nodes, non-skeletal distant metastases, and bone metastases were considered. p-value significance was defined below the 0.05 level after correction for multiple testing.

Patients' median age was 69.8 years (interquartile range (IQR): 61.8-75.1) and median PSA level at time of imaging was 0.53 ng/mL (IQR: 0.33-2.04). During follow-up, evidence of recurrence was observed in 31/44 patients. Combining MRI with [68Ga]Ga-PSMA-11 PET and [68Ga]Ga-RM2 PET resulted in sensitivity = 100% and 93.5% and specificity of 69.2% and 69.2%, respectively. When considering the individual imaging modalities, [68Ga]Ga-RM2 PET showed lower sensitivity compared to [68Ga]Ga-PSMA-11 PET and MRI (61.3% vs 83.9% and 87.1%, p = 0.046 and 0.043, respectively), while specificity was comparable among the imaging modalities (100% vs 84.6% and 69.2%, p = 0.479 and 0.134, respectively).

This study brings further evidence on the utility of fully hybrid PET/MRI for disease characterization in patients with biochemically recurrent PCa. Imaging with [68Ga]Ga-PSMA-11 PET showed high sensitivity, while the utility of [68Ga]Ga-RM2 PET in absence of a simultaneous whole-body/multiparametric MRI remains to be determined.

To describe outcomes of prostate-specific antigen (PSA)-based screening with MRI and prostate biopsies at repeat screening. DESIGN, SETTING, AND

This secondary analysis examined the population-based, screen-by-invitation STHLM3-MRI randomized clinical trial, which recruited Swedish men aged 50 to 74 years. Men were eligible for repeat screening at 2 to 3 years if they had PSA levels of 1.5 ng/mL or greater at trial inclusion, were randomized to the MRI-targeted group (including screening using biomarkers and MRI), and were not diagnosed with prostate cancer after the first screening round. Repeat screening was performed between November 10, 2021, and February 20, 2023. Data analysis was performed between May and August 2023. INTERVENTION: Participants underwent blood sampling, including PSA testing. A biparametric MRI scan was performed if PSA levels were 3 ng/mL or greater, and men with lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3 or greater were referred for targeted and systematic biopsies. MAIN OUTCOMES AND MEASURES: The primary outcome was clinically significant prostate cancer (Gleason score of ≥3 + 4). Secondary outcomes included the proportion of men with clinically insignificant cancer (Gleason score of 6), the number of elevated PSA tests, MRI scans, and biopsy procedures.

Of 7609 men from the first screening round, 2078 (27.3%) were eligible for and were invited for rescreening. Among the invitees, 1500 (72.2%) participated. Their median age was 67 (IQR, 61-72) years. Of 1094 men with PSA levels between 1.5 and 2.9 ng/mL in the first screening round, 326 (29.8%) had levels of 3 ng/mL or greater in the second round. Overall, 667 men (44.5%) had PSA levels of 3 ng/mL or greater: 617 underwent MRI (92.5%), revealing 51 (7.6%) with equivocal lesions (PI-RADS score of 3) and 33 (4.9%) with suspicious lesions (PI-RADS score of ≥4). Only 10 of 383 men (2.6%) with a prior negative MRI result had a lesion with a PI-RADS score of 4 or greater. Among the 1500 rescreened men, 48 (3.2%) had a Gleason score of 3 + 4 or greater, including 19 (1.3%) with a score of 4 + 3 or greater and 11 (0.7%) with a score of 6. CONCLUSIONS AND RELEVANCE: In this secondary analysis of the STHLM3-MRI randomized clinical trial, cancer detection during the second screening round in biennial PSA and MRI-based prostate cancer screening was limited, and the detection of low-grade tumors remained low. A substantial proportion of men exhibited elevated PSA levels during rescreening, and a considerable portion of MRI scans performed lacked lesions suggestive of cancer. Future studies should explore strategies to reduce MRI-related resource use. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03377881.

The main objective is to propose an MRI-based screening protocol, investigating the role of MRI without the injection of contrast media (bi-parametric MRI, bpMRI) as a secondary prevention test for prostate cancer (PCa) early diagnosis, comparing MRI with the prostate specific antigen (PSA) test. For this reason, preliminary results of Prostate Cancer Secondary Screening in Sapienza (PROSA) are presented, to investigate the efficiency of an MRI-based screening protocol. PROSA is a prospective, randomized, single-center study. To date, 351 men have been enrolled and blindly randomized into two different arms: (A) Men underwent a bpMRI regardless of their PSA values (175); (B) Men followed as per clinical practice: those with increased PSA (61) were referred to bpMRI, while those with normal PSA (112) were not. Men who screened positive on MRI were directed to MR-directed targeted biopsy. On arm A, 4 clinically significant PCa have been detected, while none was found on arm B (p = 0.046). To evaluate the efficiency of the screening protocol, we calculated the experimental event rate (EER, 3.6%), control event rate (CER, 1.2%.), absolute risk reduction (ARR, 2.5%), and number needed to treat (NNT, 40.3). PROSA represents an interesting experience in the field of imaging-based PCa screening. The preliminary data from this trial highlight the promising role of non-contrast MRI as a screening tool for early detection of PCa. Further data will finally validate the most appropriate screening program. CLINICAL RELEVANCE STATEMENT: PROSA depicts an interesting experience in the field of research focused on imaging-based prostate cancer screening. Its preliminary data highlight the promising role of non-contrast MRI as a screening tool for early detection of PCa. KEY POINTS: • Promotion of an MRI-based screening protocol, investigating the role of non-contrast MRI as a secondary prevention test for prostate cancer early diagnosis, comparing MRI with PSA test. • Prostate Cancer Secondary Screening in Sapienza (PROSA) represents an interesting experience in the field of research focused on imaging-based prostate cancer screening; its preliminary results indicate that it is possible to use non-contrast MRI as a screening tool for early detection of PCa. • This new approach to PCa screening could facilitate the early diagnosis of clinically significant prostate cancer while reducing the number of unnecessary prostate biopsies and the detection of clinically insignificant prostate cancer.

The role of multiparametric magnetic resonance imaging (MRI) for detecting recurrent prostate cancer after radiotherapy is unclear.

To evaluate MRI and MRI-targeted biopsies for detecting intraprostatic cancer recurrence and planning for salvage focal ablation. DESIGN, SETTING, AND

FOcal RECurrent Assessment and Salvage Treatment (FORECAST; NCT01883128) was a prospective cohort diagnostic study that recruited 181 patients with suspected radiorecurrence at six UK centres (2014 to 2018); 144 were included here. INTERVENTION: All patients underwent MRI with 5 mm transperineal template mapping biopsies; 84 had additional MRI-targeted biopsies. MRI scans with Likert scores of 3 to 5 were deemed suspicious. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: First, the diagnostic accuracy of MRI was calculated. Second, the pathological characteristics of MRI-detected and MRI-undetected tumours were compared using the Wilcoxon rank sum test and chi-square test for trend. Third, four biopsy strategies involving an MRI-targeted biopsy alone and with systematic biopsies of one to two other quadrants were studied. Fisher's exact test was used to compare MRI-targeted biopsy alone with the best other strategy for the number of patients with missed cancer and the number of patients with cancer harbouring additional tumours in unsampled quadrants. Analyses focused primarily on detecting cancer of any grade or length. Last, eligibility for focal therapy was evaluated for men with localised (≤T3bN0M0) radiorecurrent disease. RESULTS AND LIMITATIONS: Of 144 patients, 111 (77%) had cancer detected on biopsy. MRI sensitivity and specificity at the patient level were 0.95 (95% confidence interval [CI] 0.92 to 0.99) and 0.21 (95% CI 0.07 to 0.35), respectively. At the prostate quadrant level, 258/576 (45%) quadrants had cancer detected on biopsy. Sensitivity and specificity were 0.66 (95% CI 0.59 to 0.73) and 0.54 (95% CI 0.46 to 0.62), respectively. At the quadrant level, compared with MRI-undetected tumours, MRI-detected tumours had longer maximum cancer core length (median difference 3 mm [7 vs 4 mm]; 95% CI 1 to 4 mm, p < 0.001) and a higher grade group (p = 0.002). Of the 84 men who also underwent an MRI-targeted biopsy, 73 (87%) had recurrent cancer diagnosed. Performing an MRI-targeted biopsy alone missed cancer in 5/73 patients (7%; 95% CI 3 to 15%); with additional systematic sampling of the other ipsilateral and contralateral posterior quadrants (strategy 4), 2/73 patients (3%; 95% CI 0 to 10%) would have had cancer missed (difference 4%; 95% CI -3 to 11%, p = 0.4). If an MRI-targeted biopsy alone was performed, 43/73 (59%; 95% CI 47 to 69%) patients with cancer would have harboured undetected additional tumours in unsampled quadrants. This reduced but only to 7/73 patients (10%; 95% CI 4 to 19%) with strategy 4 (difference 49%; 95% CI 36 to 62%, p < 0.0001). Of 73 patients, 43 (59%; 95% CI 47 to 69%) had localised radiorecurrent cancer suitable for a form of focal ablation.

For patients with recurrent prostate cancer after radiotherapy, MRI and MRI-targeted biopsy, with or without perilesional sampling, will diagnose cancer in the majority where present. MRI-undetected cancers, defined as Likert scores of 1 to 2, were found to be smaller and of lower grade. However, if salvage focal ablation is planned, an MRI-targeted biopsy alone is insufficient for prostate mapping; approximately three of five patients with recurrent cancer found on an MRI-targeted biopsy alone harboured further tumours in unsampled quadrants. Systematic sampling of the whole gland should be considered in addition to an MRI-targeted biopsy to capture both MRI-detected and MRI-undetected disease. PATIENT SUMMARY: After radiotherapy, magnetic resonance imaging (MRI) is accurate for detecting recurrent prostate cancer, with missed cancer being smaller and of lower grade. Targeting a biopsy to suspicious areas on MRI results in a diagnosis of cancer in most patients. However, for every five men who have recurrent cancer, this targeted approach would miss cancers elsewhere in the prostate in three of these men. If further focal treatment of the prostate is planned, random biopsies covering the whole prostate in addition to targeted biopsies should be considered so that tumours are not missed.

This trial's purpose was to determine the late toxicity associated with dose escalation to Prostate Imaging Reporting and Data System (PI-RADS) III-V lesions on multiparametric magnetic resonance imaging (MRI) with an image guided combined IMRT-stereotactic body radiation therapy (SBRT) approach in men with localized prostate cancer. METHODS AND MATERIALS: In this phase 2 trial patients with localized prostate cancer with clinical tumor stage T1-T3bN0 and at least one PIRADS III-V lesion were recruited to receive 45 Gy in 25 fractions to the prostate and seminal vesicles followed by a boost of 18 Gy in 3 fractions to the prostate with a simultaneous integrated boost 21 Gy in 3 fractions to the PI-RADS lesion(s). The primary endpoint was the cumulative incidence of late grade ≥3 genitourinary and gastrointestinal toxicity by 18 months (National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0).

Overall, 50 patients were enrolled in this study, and 43 patients completed at least 18 months of follow-up. The cumulative incidence of grade 1, 2, and 3 late genitourinary toxicity at 18 months was 18%, 53%, and 2%. One patient was noted to have grade 3 hematuria and needed cystoscopy-guided cauterization. No acute grade 3 gastrointestinal or genitourinary toxicities were observed. The cumulative incidence of grade 1, 2, and 3 late gastrointestinal toxicity at 18 months was 31%, 4%, and 0%, respectively. At a median follow-up of 43.5 months, 3 patients developed biochemical recurrence, each with distant bone metastases without local or nodal recurrence. At 3 years, freedom from biochemical failure rate was 95.3% (95% CI, 89.2%-100%).

Multiparametric MRI-guided dose escalation to PI-RADS III-V lesions using a combined image guided IMRT-SBRT approach is associated with an acceptable risk of late gastrointestinal and genitourinary toxicity. The results should be interpreted with caution considering their single institutional nature, small sample size, and short follow-up and should be validated in a larger study.

In this prospective phase 2 trial, we investigated the toxicity and patient-reported quality-of-life outcomes in patients treated with stereotactic body radiation therapy (SBRT) to the prostate gland and a simultaneous focal boost to magnetic resonance imaging (MRI)-identified intraprostatic lesions while also de-escalating dose to the adjacent organs at risk. METHODS AND MATERIALS: Eligible patients included low- or intermediate-risk prostate cancer (Gleason score ≤7, prostate specific antigen ≤20, T stage ≤2b). SBRT was prescribed to 40 Gy in 5 fractions delivered every other day to the prostate, with any areas of high disease burden (MRI-identified prostate imaging reporting and data system 4 or 5 lesions) simultaneously escalated to 42.5 to 45 Gy and areas overlapping organs at risk (within 2 mm of urethra, rectum, and bladder) constrained to 36.25 Gy (n = 100). Patients without a pretreatment MRI or without MRI-identified lesions were treated to dose of 37.5 Gy with no focal boost (n = 14).

From 2015 to 2022, a total of 114 patients were enrolled with a median follow-up of 42 months. No acute or late grade 3+ gastrointestinal (GI) toxicity was observed. One patient developed late grade 3 genitourinary (GU) toxicity at 16 months. In patients treated with focal boost (n = 100), acute grade 2 GU and GI toxicity was seen in 38% and 4% of patients, respectively. Cumulative late grade 2+ GU and GI toxicities at 24 months were 13% and 5% respectively. Patient-reported outcomes showed no significant long-term change from baseline in urinary, bowel, hormonal, or sexual quality-of-life scores after treatment.

SBRT to a dose of 40 Gy to the prostate gland with a simultaneous focal boost up to 45 Gy is well tolerated with similar rates of acute and late grade 2+ GI and GU toxicity as seen in other SBRT regimens without intraprostatic boost. Moreover, no significant long-term changes were seen in patient-reported urinary, bowel, or sexual outcomes from pretreatment baseline.

Current management of prostate cancer (PC) lacks biomarker tests and diagnostic procedures that can accurately distinguish clinically significant and clinically insignificant PCs at an early stage of the disease.

To compare the Stockholm 3 (STHLM3) test and prostate-specific antigen (PSA) as entry tests for magnetic resonance imaging (MRI) in a prospective study of PC diagnosis in general practice. DESIGN, SETTING, AND

Participants were biopsy-naïve men aged 50-69 yr who had a PSA test in general practice. Participants with PSA 1-10 ng/ml also had an STHLM3 test and were referred for MRI if the STHLM311 test was positive (risk ≥11%) and/or PSA ≥3 ng/ml, and to targeted MRI-guided biopsy (MRGB) if their Prostate Imaging-Reporting and Data System (PI-RADS) score was ≥3. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the number of International Society of Urological Pathology grade group ≥2 (GG ≥2) cases detected with a positive STHLM311 test versus PSA ≥3 ng/ml. Post hoc analysis was performed using a higher STHLM3 test cutoff (risk ≥15%; positive STHLM315 test). RESULTS AND LIMITATIONS: Between January 2018 and December 2021, we recruited 1905 men. The STHLM3 test was performed in 1134 participants. Of these, 437 underwent MRI and 117 underwent MRGB, which detected 38 (32.5%) GG ≥2 and 52 (44.4%) with GG 1 cases. In comparison to PSA ≥3 ng/ml, a positive STHLM311 test increased detection of GG ≥2 from 30 to 37 cases (23.3%, 95% confidence interval [CI] 5.6-52.2%) and detection of GG 1 from 37 to 50 cases (35.1%, 95%CI 11.6-66.7%). STHLM315 positivity did not differ from PSA ≥3 ng/ml regarding detection of GG ≥2 PC (30 vs 32; 6.6%, 95% CI -8.1% to 25.9%), GG 1 PC (37 vs 37; 0.0%, 95% CI -19.6% to 25.0%), or MRGB use (88 vs 83; -5.7%, 95% CI -17.9% to 7.4%), but reduced MRI scans from 320 to 236 (-26.2%, 95% CI -33.1% to -18.9%).

The STHLM311 test improved sensitivity but not specificity for detection of GG ≥2 PC in the clinical setting of nonsystematic PC testing in general practice. Further studies are needed to validate a possible benefit of using a higher cutoff for STHLM3 positivity as an entry test for MRI. PATIENT SUMMARY: We used a test called STHLM3 for detection of prostate cancer in general practice and compared its performance to the conventional PSA (prostate-specific antigen) test. We found that STHLM3 test results of 11% or above were not better at selecting men for MRI (magnetic resonance imaging) scans than the PSA test with a cutoff of 3 ng/ml or above. Analysis suggested that a higher cutoff for a positive STHLM3 test may improve selection of men for MRI scans, but further validation is needed.

This study aimed to develop and validate a model based on biparametric magnetic resonance imaging (bpMRI) for the detection of clinically significant prostate cancer (csPCa) in biopsy-naïve patients.

This retrospective study included 324 patients who underwent bpMRI and MRI targeted fusion biopsy (MRGB) and/or systematic biopsy, of them 217 were randomly assigned to the training group and 107 were assigned to the validation group. We assessed the diagnostic performance of three bpMRI-based scorings in terms of sensitivity and specificity. Subsequently, 3 models (Model 1, Model 2, and Model 3) combining bpMRI scorings with clinical variables were constructed and compared with each other using the area under the receiver operating characteristic (ROC) curves (AUC). The statistical significance of differences among these models was evaluated using DeLong's test.

In the training group, 68 of 217 patients had pathologically proven csPCa. The sensitivity and specificity for Scoring 1 were 64.7% (95% CI 52.2%-75.9%) and 80.5% (95% CI 73.3%-86.6%); for Scoring 2 were 86.8% (95% CI 76.4%-93.8%) and 73.2% (95% CI 65.3%-80.1%); and for Scoring 3 were 61.8% (95% CI 49.2%-73.3%) and 80.5% (95% CI 73.3%-86.6%), respectively. Multivariable regression analysis revealed that scorings based on bpMRI, age, and prostate-specific antigen density (PSAD) were independent predictors of csPCa. The AUCs for the 3 models were 0.88 (95% CI 0.83-0.93), 0.90 (95% CI 0.85-0.94), and 0.88 (95% CI 0.83-0.93), respectively. Model 2 showed significantly higher performance than Model 1 (P = 0.03) and Model 3 (P < 0.01).

All three scorings had favorite diagnostic accuracy. While in conjunction with age and PSAD the prediction power was significantly improved, and the Model 2 that based on Scoring 2 yielded the highest performance.

Targeting biopsy (TBx) of suspicious lesions combined with random systematic biopsy (SBx) improves detection rates of prostate cancer (PCa) during magnetic resonance imaging (MRI)/ultrasound (US) fusion prostate biopsy. However, this combination increases the number of biopsy cores, prolongs the procedure time, and increases complications and costs, leading to the overdiagnosis of clinically insignificant PCa (ciPCa). This study aims to evaluate the optimal sampling design to achieve a detection rate of clinically significant PCa (csPCa) equal to standard TBx with SBx with fewer biopsy cores.

Of 508 consecutive men who underwent transperineal MRI/US fusion prostate biopsy at our center between January 2020 and December 2022, 364 patients with a single unilateral suspicious lesion on MRI were included in the study. Three biopsy strategies were randomly selected to evaluate the diagnostic accuracy of PCa detection: (1) TBx with ipsilateral SBx, (2) TBx with contralateral SBx, and (3) TBx only. The PCa detection sensitivity for selected biopsy strategies was compared with the reference standards. The significance of differences in cancer detection between sampling schemes was determined using McNemar's test.

PCa was diagnosed in 182 of 364 men using TBx with bilateral SBx. International Society of Urological Pathology grade group (ISUP GG) ≥ 2 and ISUP GG ≥ 3 PCa was detected in 84/364 (23.1%) and 42/364 (11.5%), respectively, while ISUP GG 1 PCa was diagnosed in 98/364 (26.9%). Combining TBx with ipsilateral SBx detected 94.5% of all, 98.8% of ISUP GG ≥ 2, 100% of ISUP GG ≥ 3, and 89.8% of ISUP GG 1 PCa. TBx with contralateral SBx detected fewer csPCa (91.7% vs. 98.8%, p = 0.03), as did TBx alone (90.5 vs. 98.8, p = 0.008).

Our study demonstrates that TBx with ipsilateral SBx performed around the multiparametric MRI-suspected lesion in transperineal MRI/US biopsy of the prostate achieves a very high detection rate for csPCa (ISUP ≥ 2) without compromising the detection of increased risk PCa (ISUP ≥ 3). In addition, this strategy reduces the number of biopsy cores by 8-10 per patient, procedure time, and pathology processing costs and decreases ciPCa detection.

Ultra-hypofractionated image-guided stereotactic body radiotherapy (SBRT) is increasingly used for definitive treatment of localized prostate cancer. Magnetic resonance imaging-guided radiotherapy (MRgRT) facilitates improved visualization, real-time tracking of targets and/or organs-at-risk (OAR), and capacity for adaptive planning which may translate to improved targeting and reduced toxicity to surrounding tissues. Given promising results from NRG-GU003 comparing conventional and moderate hypofractionation in the post-operative setting, there is growing interest in exploring ultra-hypofractionated post-operative regimens. It remains unclear whether this can be done safely and whether MRgRT may help mitigate potential toxicity. SHORTER (NCT04422132) is a phase II randomized trial prospectively evaluating whether salvage MRgRT delivered in 5 fractions versus 20 fractions is non-inferior with respect to gastrointestinal (GI) and genitourinary (GU) toxicities at 2-years post-treatment.

A total of 136 patients will be randomized in a 1:1 ratio to salvage MRgRT in 5 fractions or 20 fractions using permuted block randomization. Patients will be stratified according to baseline Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domain scores as well as nodal treatment and androgen deprivation therapy (ADT). Patients undergoing 5 fractions will receive a total of 32.5 Gy over 2 weeks and patients undergoing 20 fractions will receive a total of 55 Gy over 4 weeks, with or without nodal coverage (25.5 Gy over 2 weeks and 42 Gy over 4 weeks) and ADT as per the investigator's discretion. The co-primary endpoints are change scores in the bowel and the urinary domains of the EPIC. The change scores will reflect the 2-year score minus the pre-treatment (baseline) score. The secondary endpoints include safety endpoints, including change in GI and GU symptoms at 3, 6, 12 and 60 months from completion of treatment, and efficacy endpoints, including time to progression, prostate cancer specific survival and overall survival.

The SHORTER trial is the first randomized phase II trial comparing toxicity of ultra-hypofractionated and hypofractionated MRgRT in the salvage setting. The primary hypothesis is that salvage MRgRT delivered in 5 fractions will not significantly increase GI and GU toxicities when compared to salvage MRgRT delivered in 20 fractions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04422132. Date of registration: June 9, 2020.

We report herein the impact of focal therapy (FT) on multi-domain functional outcomes in a Phase II prospective clinical trial (NCT04138914) in focal cryotherapy for clinically significant prostate cancer (csPCa).

The primary outcome was the detection of a ≥5 point deterioration in any of the four main expanded prostate index composite (EPIC) functional domains. Pretreatment multiparametric magnetic resonance imaging (mpMRI) and transperineal targeted and systematic saturation biopsy were used to select patients with prostate-specific antigen (PSA)≤20 ng/mL, Gleason grade group (GG) ≤4, mpMRI lesion volume ≤ 3 mL (for a single lesion) or ≤1.5 mL (where two lesions were present). Focal cryotherapy was performed with a minimum 5 mm margin around each target lesion. EPIC scores were obtained at baseline and posttreatment at 1, 3, 6, and 12 months. Mandatory repeat mpMRI and prostate biopsy were performed at 12 months to determine the infield and outfield recurrence.

Twenty-eight patients were recruited. The mean age was 68 years, with PSA of 7.3 ng/mL and PSA density of 0.19 ng/mL2 . No Clavien-Dindo ≥3 complications occurred. Transient worsening of EPIC urinary (mean diff 16.0, p < 0.001, 95% confidence interval [CI]: 8.8-23.6) and sexual function scores (mean diff 11.0, p:0.005, 95% CI: 4.0-17.7) were observed at 1-month posttreatment, with recovery by Month 3. A subgroup who had ablation extending to the neurovascular bundle had a trend to delayed recovery of sexual function to Month 6. At 12-month repeat mpMRI and biopsy, 22 patients (78.6%) had no detectable csPCa. Of the six patients (21.4%) who had csPCa recurrences, four were GG2, one GG3, and one GG4. Four patients underwent repeat FT, one underwent radical prostatectomy, while the remaining one patient with low-volume GG2 cancer opted for active surveillance.

FT using cryotherapy was associated with a transient deterioration of urinary and sexual function with resolution at 3 months posttreatment and with reasonable early efficacy in well-selected csPCa patients.

We examined the interfractional variations of clinical target volumes (CTVs), planning target volumes (PTVs), and organs-at-risk (OARs) in patients receiving MRI-guided stereotactic body radiotherapy (SBRT) to the prostate bed and evaluated the potential role of adaptive planning.

31 patients received 30-34 Gy in five fractions to the prostate bed on a phase II clinical trial. OARs, CTVs, and PTVs were retrospectively contoured on daily pretreatment MRIs (n = 155). Geometric comparisons were made between initial planning contours and daily pretreatment contours. Predicted treatment plans for each fraction were evaluated using the following constraints: CTV V95%>93%, PTV V95%>90%, bladder Dmax < 36.7 Gy, bladder V32.5 Gy < 35%, rectum Dmax < 36.7 Gy, rectum V27.5 Gy < 45%, rectum 32.5 Gy < 30%, and rectal wall V24Gy < 50%. Adaptive planning was simulated for all fractions that failed to meet these criteria. Plans were then re-evaluated.

Median change in volume was 0.48% for CTV, -24.5% for bladder, and 6.95% for rectum. Median DSC was 0.89 for CTV, 0.79 for bladder, and 0.76 for rectum. 145/155 fractions (93.5%) met CTV V95%>93%. 75/155 fractions (48.4%) failed at least one OAR dose constraint. Overall, 83/155 fractions (53.5%) met criteria for adapting planning. This affected 24/31 patients (77.4%). Following adaptive planning, all fractions met CTV V95%>93% and PTV V95%>90% and 120/155 fractions (77.4%) met all OAR constraints.

Due to significant interfractional variations in anatomy, a majority of fractions failed to meet both target volume and OAR constraints. However, adaptive planning was effective in overcoming these anatomic changes. Adaptive planning should be routinely considered in prostate bed SBRT.

To compare the correlation of Gleason score (GS) and ISUP grade determined by prostate biopsies (PBx) and radical prostatectomy (RP) specimens according to the biopsy technique: ultrasound randomised (RBx) vs. MRI/ultrasound fusion targeted (TBx).

Between March 2013 and June 2018, we retrospectively included patients who underwent RP for prostate cancer (PCa) histopathologically proven by RBx and/or TBx. All patients had a prebiopsy MRI by a single radiologist (using PI-RADS score), then transrectal RBx (12cores, blinded to MRI lesions) and TBx (2-4 cores/target) with elastic MRI/ultrasound fusion (UroStation™, Koelis, Grenoble, France). Histological findings were compared: PBx vs. RP.

One hundred and four patients underwent RP after RBx and/or TBx. ISUP concordance rate was better with the association RBx+TBx 49% (51/104) vs. 43.3% with TBx (P=0.07) and 43.3% with RBx (P=0.13). With RBx, 50% of the patients were downgraded (52/104) against 42.3% (44/104) with TBx (P=0.088). The association RBx+TBx significantly decreased the rate of downgrading of the ISUP score compared to the ISUP score of RP 35.6% (37/104) vs. RBx (50%, P=0.0001) and vs. TBx (42.3%, P=0.016).

In half of cases, the ISUP score was underestimated in RBx compared to RP specimens. Adding TBx to RBx significantly reduced downgrading. The combination of both biopsy techniques appeared to be the best protocol to get closer to ISUP score and GS of the RP specimens. LEVEL OF EVIDENCE: C.

This is the first report of the 2SMART Phase II trial evaluating the safety of two-fraction stereotactic ablative radiotherapy (SABR) with focal boost to magnetic resonance imaging (MRI) defined dominant intra-prostatic lesion (DIL) for localised prostate cancer.

Men with low or intermediate risk prostate cancer were eligible for the study. The gross tumour volume (GTV) was MRI-defined DIL, and the clinical target volume (CTV) was entire prostate gland. The planning target volume (PTV) was a 2 mm expansion anteroposterior and lateral, and 2.5 mm superoinferior. The prescribed dose was 32 Gy to GTV, and 26 Gy to CTV. Primary endpoint was minimal clinically important change (MCIC) in quality of life (QOL) within 3-months of SABR, assessed using the EPIC-26 questionnaire. Secondary endpoints were acute and late toxicities (assessed using CTCAEv4), PSA nadir, and biochemical failure (based on Phoenix criteria).

Thirty men were enrolled in the study - 2 (7%) had low-risk and 28 (93%) had intermediate risk prostate cancer. The median follow-up was 44 months (range:39-49 months). The median PSA nadir was 0.25 ng/mL, with median time to nadir of 37 months. One patient (3%) had biochemical failure at 44 months post-treatment. Ten (33%), six (20%), and three (10%) men had acute MCIC in urinary, bowel, and sexual QOL domains respectively. No acute or late grade ≥ 3 urinary or bowel toxicities were observed.

This novel protocol of two-fraction prostate SABR with MRI-defined DIL boost is a safe approach for dose-escalation, with minimal impact on acute QOL and no grade ≥ 3 toxicities.

The significance of metastasis-directed therapy for oligometastatic prostate cancer has been widely discussed, and targeted therapy for progressive sites is a feasible option as a multidisciplinary treatment for castration-resistant prostate cancer (CRPC). When oligometastatic CRPC with only bone metastases progresses after targeted therapy, it tends to progress as multiple bone metastases. The progression of oligometastatic CRPC after targeted therapy may be due in part to the presence of micrometastatic lesions that, though undetected on imaging, were present prior to targeted therapy. Thus the systemic treatment of micrometastases in combination with targeted therapy for progressive sites is expected to enhance the therapeutic effect. Radium-223 dichloride (radium-223) is a radiopharmaceutical that selectively binds to sites of increased bone turnover and inhibits the growth of adjacent tumor cells by emitting alpha rays. Therefore, for oligometastatic CRPC with only bone metastases, radium-223 may enhance the therapeutic effect of radiotherapy for active metastases.

This phase II, randomized trial of Metastasis-Directed therapy with ALpha emitter radium-223 in men with oligometastatic CRPC (MEDAL) is designed to assess the utility of radium-223 in combination with metastasis-directed radiotherapy in patients with oligometastatic CRPC confined to bone. In this trial, patients with oligometastatic CRPC with three or fewer bone metastases on whole-body MRI with diffusion-weighted MRI (WB-DWI) will be randomized in a 1:1 ratio to receive radiotherapy for active metastases plus radium-223 or radiotherapy for active metastases alone. The prior use of androgen receptor axis-targeted therapy and prostate-specific antigen doubling time will be used as allocation factors. The primary endpoint will be radiological progression-free survival against progression of bone metastases on WB-DWI.

This will be the first randomized trial to evaluate the effect of radium-223 in combination with targeted therapy in oligometastatic CRPC patients. The combination of targeted therapy for macroscopic metastases with radiopharmaceuticals targeting micrometastasis is expected to be a promising new therapeutic strategy for patients with oligometastatic CRPC confined to bone. Trial registration Japan Registry of Clinical Trials (jRCT) (jRCTs031200358); Registered on March 1, 2021, https://jrct.niph.go.jp/latest-detail/jRCTs031200358.

Artificial intelligence ultrasound of prostate (AIUSP)-targeted biopsy has been used for prostate cancer (PCa) diagnosis. The objective of this prospective multi-center head-to-head clinical randomized comparative trail (RCT) is to compare PCa detection rate in the TRUS-guided 12-core standard systematic biopsy (TRUS-SB) group and cognitive fused mpMRI-guided 12-core biopsy (mpMRI) group against AIUSP group.

Four hundred patients were randomized to three arms and underwent biopsies by TRUS-SB (n = 133), mpMRI (n = 134), and AIUSP (n = 133) between January 2015 and December 2017. In TRUS-SB group, a standard 12-core systematic biopsy was performed. In mpMRI group, mpMRI-suspicious lesions (PI-RADS 3-5) were targeted by 2-core biopsy followed by a 10-core systematic biopsy. Otherwise, 12-core systematic biopsy was performed. In AIUSP group, a 6-core targeted biopsy was performed. The primary endpoint was PCa detection rate.

AIUSP detected the highest rate of PCa (66/133, 49.6%) compared to TRUS-SB (46/133, 34.6%, p = 0.036) and mpMRI (48/134, 35.8%, p = 0.052). Compared to TRUS-SB (35/133, 26.3%) and mpMRI (31/134, 23.1%) groups, clinically significant PCa (csPCa) detection rate was 32.3% (43/133) in AIUSP group. Overall biopsy core positive rate in the TRUS-SB group (11.0%, 176/1598) and in the mpMRI group (12.7%, 204/1608) was significantly lower than that in the AIUSP group (22.7%, 181/798, p < 0.001).

AIUSP detected the highest rate of overall and significant PCa compared to TRUS-SB and mpMRI, and could be used as an alternative to systematic biopsy in the future. REGISTRATION: This trial was registered in ISRCTN (ISRCTN18033113).

To assess the proportion of clinically significant (cs) prostate cancer (PCa) found during follow-up in patients with negative systematic biopsy (SB) followed by non-suspicious multiparametric magnetic resonance imaging (mpMRI) and persistent clinical suspicion of PCa compared to the general population. PATIENTS AND

A prospective study in a subgroup of patients from a multicentre randomized controlled trial was conducted between 2014 and 2017, including 665 men with prior negative SB with a persistent elevated prostate-specific antigen and/or suspicious digital rectal examination undergoing mpMRI. All patients with negative SB and Prostate Imaging-Reporting and Data System (PI-RADS) ≤2 on mpMRI entered biochemical follow-up. Follow-up data until December 2021 were collected by reviewing institutional hospital records and the Dutch Pathology Registry (PALGA). The primary outcome was the observed number of csPCa (Gleason ≥3 + 4/International Society of Urological Pathology grade group ≥2) cases during follow-up compared to the expected number in the general population (standardized incidence ratio [SIR]).

In total, 431 patients had non-suspicious mpMRI and entered biochemical follow-up. After a median (interquartile range) follow-up of 41 (23-57) months, 38 patients were diagnosed with PCa, of whom 13 (3.0%) had csPCa. The SIR for csPCa was 4.3 (95% confidence interval 2.3-7.4; total excess of eight cases). A higher risk of a positive biopsy for (cs)PCa based on the European Randomized Study of Screening for Prostate Cancer risk calculator and a suspicious repeat MRI (PI-RADS ≥3) were significant predictive factors for csPCa.

After negative prior biopsy and non-suspicious mpMRI the risk of csPCa is low. However, compared to the general population, the risk of csPCa is increased despite the high negative predictive value of mpMRI. More research focusing on biochemical and image-guided risk-adapted diagnostic surveillance strategies is warranted.

Safety and efficacy of ultrasound prostate ablation for radiorecurrent prostate cancer (PCa) in the presence of gold fiducial markers has not been previously reported.

To evaluate safety, functional, and early-stage oncological outcomes for patients with gold fiducial markers undergoing salvage magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (sTULSA) for radiorecurrent PCa.

Data were acquired from an ethics-approved, single-center phase-1 study. Eight patients with 18 total gold fiducial markers inside the planned treatment volume were identified. MRI controls were performed at three and 12 months, followed by PSMA-PET-CT imaging and biopsies at 12 months. A control cohort of 13 patients who underwent sTULSA without markers were also identified for safety profile comparison. Adverse events were reported using the Clavien-Dindo classification, and questionnaires including EPIC-26, IPSS, and IIEF-5 were collected.

Of 18 markers, 2 (11%) were directly responsible for poor ultrasound penetration. However, there were no local recurrences at 12 months. PSA, prostate volume, and non-perfused volume all decreased over time. At 12 months, 11/18 (61%) of fiducial markers had disappeared via sloughing. The adverse event profile was similar between both patient cohorts, and when controlled for ablation type, no statistical difference in functional outcomes between the two cohorts was observed.

Patients with radiorecurrent PCa with intraprostatic gold fiducial markers can be successfully treated with TULSA. The early-stage efficacy of sTULSA for patients with intraprostatic gold markers is encouraging and the safety profile is unaffected by marker presence.

In the era of mpMRI guided target fusion biopsy (FB), the role of concomitant standard biopsy (SB) in naïve patients still remains under scrutiny. The aim of this study was to compare the detection rate (DR) of clinically significant prostate cancer (csPCa) in biopsy naïve patients with positive mpMRI who underwent FB alone (Arm A) vs FB+SB (Arm B). Secondary objectives were to compare the incidence of complications, the overall PCa DR and the biopsy results with final pathological findings after robotic prostatectomy (RARP).

This is a single center prospective non-inferiority parallel two arms (1:1) randomized control trial (ISRCTN registry number ISRCTN60263108) which took place at San Luigi Gonzaga University Hospital, Orbassano (Turin, Italy) from 4/2019 to 10/2021. Eligible participants were all adults aged<75 years old, biopsy naïve, with serum PSA<15 ng/mL and positive mpMRI (Pi-Rads V.2>3). FB was performed under ultrasound guidance using the BioJet fusion system; four to six target samples were obtained for each index lesion. SB was performed in accordance with the protocol by Rodríguez-Covarrubias. RARP with total anatomical reconstruction was carried out when indicated. DR of PCa and csPCA (Gleason Score >7) were evaluated. Post-biopsy complications according to Clavien-Dindo were recorded. Concordance between biopsy and RARP pathological findings was evaluated. Fisher's Exact test and Mann-Whitney test were applied; furthermore, Logistic Principal Component Analysis (LogPCA) and Pearson's correlation method, in terms of correlation funnel plots, were performed to explore data in a multivariate way.

201 and 193 patients were enrolled in Arm A and B, respectively. csPCa DR was 60.2% vs. 60.6% in Arm A and B respectively (Δ 0.4%; P=0.93); whilst overall PCa DR was 63.7% vs. 71.0% (Δ 7.3%; P=0.12). However, in a target only setting, the addition of SB homolaterally to the index lesion reaching a non-inferior performance compared to the combined sampling (Δ PCa DR 3%). Although the differences of 7.3% in PCa DR, during RARP were registered similar nerve sparing rate (P=0.89), positive surgical margins (P=0.67) and rate of significant upgrading (P=0.12). LogPCA model showed no distinction between the two cohorts; and Pearson's correlation values turned to be between -0.5 and +0.5. In Arm B, the lesion diameter <10 mm is the only predictive variable of positive SB only for PCa (P=0.04), with an additional value +3% for PCa DR.

In biopsy naïve patients, FB alone is not inferior to FB+SB in detecting csPCa (Δ csPCa DR 0.4%). Δ 7.3% in overall PCa DR was registered between the two Arms, however the addition of further standard samples homolaterally to mp-MRI index lesion improved the overall PCa DR of FB only sampling (Δ PCa DR 3%). The omission of SB did not influence the post-surgical outcomes in terms of NS approach, PSMr and upgrading/downgrading.

MRI-targeted biopsy (MRTB) improves the clinically significant prostate cancer (csPCa) detection rate with fewer biopsy cores in men with suspected PCa. However, whether concurrent systematic biopsy (SB) can be avoided in patients undergoing MRTB remains unclear.

To evaluate the potential value of MRI-based radiomics models in avoiding unnecessary SB in biopsy-naïve patients. STUDY TYPE: Retrospective. POPULATION: A total of 226 patients (mean age 66.6 ± 9.02 years) with suspicion of PCa (PI-RADS score ≥ 3) and received combined cognitive MRTB with SB were retrospectively recruited and randomly divided into training (N = 180) and test (N = 46) cohorts at an 8:2 ratio. FIELD STRENGTH/SEQUENCE: A 3.0 T, biparametric MRI (bpMRI) including T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) map. ASSESSMENT: The whole prostate gland (PG) and the index lesion (IL) were delineated. Three radiomics models of bpMRIPG , bpMRIIL , and bpMRIPG+IL were constructed, respectively, and the performance of each radiomics model was compared with that of PI-RADS assessment. STATISTICAL TESTS: The least absolute shrinkage and selection operator (LASSO) regression method was used to select texture features. The area under the curve (AUC) and decision curve analysis were used to estimate the models.

The bpMRIPG+IL radiomics model exhibited good discrimination, calibration, and net benefits, which would reduce the SB biopsy in 71.2% and 71.4% of men with PI-RADS ≥ 5 lesions in the training and test cohorts, respectively. DATA

A bpMRIPG+IL radiomics model may outperform PI-RADS category in help reducing unnecessary SB in biopsy-naïve patients. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 6.

Multiparametric magnetic resonance imaging (mpMRI) and targeted biopsy (TB) facilitate accurate detection of clinically significant prostate cancer (csPC). However, it remains unclear how targeted cores should be applied for accurate diagnosis of csPC.

To assess csPC detection rates for two target-directed MRI/transrectal ultrasonography (TRUS) fusion biopsy approaches, conventional TB and target saturation biopsy (TS). DESIGN, SETTING, AND

This was a prospective single-center study of outcomes for transperineal MRI/TRUS fusion biopsies for 170 men. Half of the men (n = 85) were randomized to conventional TB with four cores per lesion and half (n = 85) to TS with nine cores. Biopsies were performed by three experienced board-certified urologists. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PC and csPC (International Society of Urological Pathology grade group ≥2) detection rates for systematic biopsy (SB), TB, and TS were analyzed using McNemar's test for intrapatient comparisons and Fisher's exact test for TS versus TB. A combination of targeted biopsy (TS or TB) and SB served as the reference. RESULTS AND LIMITATIONS: According to the reference, csPC was diagnosed for 57 men in the TS group and 36 men in the TB group. Of these, TS detected 57/57 csPC cases and TB detected 33/36 csPC cases (p = 0.058). Detection of Gleason grade group 1 disease was 10/12 cases with TS and 8/17 cases with TB (p = 0.055). In addition, TS detected 97% of 63 csPC lesions, compared to 86% with TB (p = 0.1). Limitations include the single-center design, the limited generalizability owing to the transperineal biopsy route, the lack of central review of pathology and radical prostatectomy correlation, and uneven distributions of csPC prevalence, Prostate Imaging-Reporting and Data System (PI-RADS) 5 lesions, men with two or more PI-RADS ≥3 lesions, and prostate-specific antigen density between the groups, which may have affected the results.

In our study, rates of csPC detection did not significantly differ between TS and TB. PATIENT SUMMARY: In this study, we investigated two targeted approaches for taking prostate biopsy samples after observation of suspicious lesions on prostate scans. We found that the rates of detection of prostate cancer did not significantly differ between the two approaches.

The bombesin derivative RM2 is a GRPr antagonist with strong binding affinity to prostate cancer (PCa). In this study, the impact of [68Ga]Ga-RM2 positron emission tomography-computed tomography (PET-CT) for the detection of primary PCa was compared with that of [18F]FCH PET-CT and multiparametric magnetic resonance imaging (mpMRI).

This phase I/II study was conducted in 30 biopsy-positive PCa subjects. The patients were stratified into high (10 patients), intermediate (10 patients), and low risk (10 patients) for extraglandular metastases as defined by National Comprehensive Cancer Network (NCCN) criteria (NCCN Clinical Practice Guidelines in Oncology, 2016). The prostate gland was classified in 12 anatomic segments for data analysis of the imaging modalities as well as histopathologic findings. The segment with the highest radiotracer uptake was defined as the "index lesion." All cases were scheduled to undergo prostatectomy with pelvic lymph node (LN) dissection in intermediate- and high-risk patients. Intraprostatic and pelvic nodal [68Ga]Ga-RM2 and [18F]FCH PET-CT findings were correlated with mpMRI and histopathologic results.

Of the 312 analyzed regions, 120 regions (4 to 8 lesions per patient) showed abnormal findings in the prostate gland. In a region-based analysis, overall sensitivity and specificity of [68Ga]Ga-RM2 PET-CT in the detection of primary tumor were 74% and 90%, respectively, while it was 60% and 80% for [18F]FCH PET-CT and 72% and 89% for mpMRI. Although the overall sensitivity of [68Ga]Ga-RM2 PET-CT was higher compared to that of [18F]FCH PET-CT and mpMRI, the statistical analysis showed only significant difference between [68Ga]Ga-RM2 PET-CT and [18F]FCH PET-CT in the intermediate-risk group (p = 0.01) and [68Ga]Ga-RM2 PET-CT and mpMRT in the high-risk group (p = 0.03). In the lesion-based analysis, there was no significant difference between SUVmax of [68Ga]Ga-RM2 and [18F]FCH PET-CT in the intraprostatic malignant lesions ([68Ga]Ga-RM2: mean SUVmax: 5.98 ± 4.13, median: 4.75; [18F]FCH: mean SUVmax: 6.08 ± 2.74, median: 5.5; p = 0.13).

[68Ga]Ga-RM2 showed promising PET tracer for the detection of intraprostatic PCa in a cohort of patients with different risk stratifications. However, significant differences were only found between [68Ga]Ga-RM2 PET-CT and [18F]FCH PET-CT in the intermediate-risk group and [68Ga]Ga-RM2 PET-CT and mpMRT in the high-risk group. In addition, GRP-R-based imaging seems to play a complementary role to choline-based imaging for full characterization of PCa extent and biopsy guidance in low- and intermediate-metastatic-risk PCa patients and has the potential to discriminate them from those at higher risks. KEY POINTS: • [68Ga]Ga-RM2 is a promising PET tracer with a high detection rate for intraprostatic PCa especially in intermediate-risk prostate cancer patients. • GRPr-based imaging seems to play a complementary role to choline-based or PSMA-based PET/CT imaging in selected low- and intermediate-risk PCa patients for better characterization and eventually biopsy guidance of prostate cancer disease.

NCT03253744 was a phase 1 trial to identify the maximum tolerated dose (MTD) of image-guided, focal, salvage stereotactic body radiation therapy (SBRT) for patients with locally radiorecurrent prostate cancer. Additional objectives included biochemical control and imaging response. METHODS AND MATERIALS: The trial design included 3 dose levels (DLs): 40 Gy (DL1), 42.5 Gy (DL2), and 45 Gy (DL3) in 5 fractions delivered ≥48 hours apart. The prescription dose was delivered to the magnetic resonance- and prostate-specific membrane antigen imaging-defined tumor volume. Dose escalation followed a 3+3 design with a 3-patient expansion at the MTD. Toxicities were scored until 2 years after completion of SBRT using Common Terminology Criteria for Adverse Events, version 5.0, criteria. Escalation was halted if 2 dose-limiting toxicities occurred, defined as any persistent (>4 days) grade 3 toxicity occurring within the first 3 weeks after SBRT and any grade 3 genitourinary (GU) or grade 4 gastrointestinal (GI) toxicity thereafter.

Between August 2018 and May 2022, 8 patients underwent salvage focal SBRT, with a median follow-up of 35 months. No dose-limiting toxic effects were observed on DL1. Two patients were enrolled in DL2 and experienced grade 3 GU toxicities, prompting de-escalation and expansion (n = 6) at the MTD (DL1). The most common toxicities observed were grade ≥2 GU toxicities, with only a single grade 2 GI toxicity and no grade ≥3 GI toxicities. One patient experienced biochemical failure (prostate-specific antigen nadir + 2.0) at 33 months.

The MTD for focal salvage SBRT for isolated intraprostatic radiorecurrence was 40 Gy in 5 fractions, producing a 100% 24-month biochemical progression free survival, with 1 poststudy failure at 33 months. The most frequent clinically significant toxicity was late grade ≥2 GU toxicity.

To report acute toxicity and health-related quality of life (HRQoL) outcomes of a phase II clinical trial of magnetic resonance imaging (MRI)-guided prostate high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy. METHODS AND MATERIALS: Patients with intermediate- and high-risk prostate cancer (PCa) were eligible. Treatment consisted of a single 15 Gy MRI-guided HDR-BT followed by external beam radiotherapy (37.5-46 Gy depending on their risk category). Dosimetry, toxicity and HRQoL outcomes were collected prospectively at baseline, 1 and 3 months using Common Terminology Criteria for Adverse Events Version 4.0 and the expanded PCa index composite, respectively. General linear mixed modeling was conducted to assess the changes in expanded PCa index composite domain scores over time. A minimally important difference was defined as a deterioration of HRQoL scores at 3 months compared to baseline ≥ 0.5 standard deviation. A p value ≤ 0.05 was considered statistically significant.

Sixty-one patients were included. Acute grade (G)2 urinary toxicity was observed in 18 (30%) patients while 1 (2%) patient had G3 toxicity, and none had G4 toxicity. Two patients had an acute urinary retention. G2 gastrointestinal toxicity was reported by 5 (8%) patients with no G3-4. Compared to baseline, urinary HRQoL scores significantly declined at 1 month (p < 0.001) but recovered at 3 months (p > 0.05). Bowel (p < 0.001) and sexual (p < 0.001) domain scores showed a significant decline over the 3-month follow-up period. At 3 months, 44%, 49% and 57% of patients reported a minimally important difference respectively in the urinary bowel and sexual domains.

MRI-guided HDR-BT boost is a safe and well tolerated treatment of intermediate- and high-risk PCa in the acute setting. A longer follow-up and a comparison to ultrasound-based HDR-BT are needed to assess the potential benefit of MRI-guided prostate HDR-BT.