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Background: Multiparametric magnetic resonance imaging (mpMRI) is pivotal in prostate cancer (PCa) diagnosis, but some clinically significant (cs) PCa remain undetected. This study aims to understand the pathological and molecular basis for csPCa visibility at mpMRI., Methods: We performed a retrospective matched-pair cohort study, including patients undergoing radical prostatectomy (RP) for csPCa (i.e., ISUP grade group ≥ 2) from 2015 to 2020, in our tertiary-referral center. We screened for inclusion in the "mpMRI-invisible" cohort all consecutive men (N = 45) having a negative preoperative mpMRI. The "mpMRI-visible" cohort was matched based on age, PSA, prostate volume, ISUP grade group. Included patients underwent radiological and pathological open-label revisions and characterization of the tumor mRNA expression profile (analyzing 780 gene transcripts, signaling pathways, and cell-type profiling). We compared the clinical-pathological variables and the gene expression profile between matched pairs. The analysis was stratified according to histological characteristics and lesion diameter., Results: We included 34 patients (17 per cohort); mean age at RP and PSA were 70.5 years (standard deviation [SD] = 7.7), 7.1 ng/mL (SD = 3.3), respectively; 65% of men were ISUP 2. Overall, no significant differences in histopathological features, tumor diameter and location, mRNA profile, pathways, and cell-type scores emerged between cohorts. In the stratified analysis, an upregulation of cell adhesion and motility, of extracellular matrix remodeling and of metastatic process pathways was present in specific subgroups of mpMRI-invisible cancers., Conclusions: No PCa pathological or gene-expression hallmarks explaining mp-MRI invisibility were identified. Aggressive features can be present both in mpMRI-invisible and -visible tumors., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)

The role of neoadjuvant and adjuvant hormonal or chemotherapy-based treatments before or after radical prostatectomy in localized or locally advanced high-risk prostate cancer (PCa) is currently debatable. European guidelines recommend adjuvant androgen deprivation therapy (ADT) only in pN1 patients after extended pelvic lymph node dissection based on outdated evidence on standard hormonal agents. The introduction of new-generation androgen receptor targeting agents (ARTAs) has revolutionized the treatment of metastatic PCa and might also impact the perioperative management of patients with high-risk localized disease. In the last years, a renewed interest has also arisen in chemotherapy-based neoadjuvant or adjuvant treatments alone or in combination with ADT and/or ARTAs. In the present review, we gathered the current evidence on the oncological outcomes of neoadjuvant and adjuvant systemic treatments in surgically treated patients with localized or locally advanced PCa. Despite mild benefits in terms of pathologic responses or oncological outcomes reported in some studies investigating ADT and/or chemotherapy in this setting of patients, strong evidence to support their use in clinical practice is lacking. Promising data in favor of ARTAs have been gathered from phase II trials and prospective series, but definitive results from phase III trials are awaited to confirm these findings.

Introduction: The preservation of the bladder neck during robot-assisted radical prostatectomy (RARP) could improve urinary continence recovery and limit the risk of positive surgical margins (PSMs). We refined our lateral approach to the bladder neck technique and compared its outcomes with those of the standard anterior approach., Material and Methods: From a retrospective analysis of 599 consecutive RARPs, 171 patients treated with the lateral and 171 patients treated with the anterior approach were pair-matched 1:1 on the basis of age, grade, and pathological stage. We described our surgical technique and compared the two approaches in terms of basal PSMs, recovery of urinary continence, and complications., Results: As compared to the anterior approach, the lateral approach had shorter operative times and comparable rates of basal PSMs and postoperative complications. The rates of urinary continence after one, three, and 12 months were comparable between the two groups and were generally higher in localized disease. At regression analysis, predictors of urinary incontinence were only age, pathological stage T3b, ISUP grade 5 and nerve-sparing surgery., Conclusions: The lateral approach leads to an anatomical dissection of the bladder neck without increasing the risk of PSMs. However, no significant benefits in terms of continence recovery were demonstrated over the standard anterior approach.

Background and Objective: Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes., Material and Methods: Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value ≥ 0.1 ng/ml, at first PSA-measurement after salvage RP., Results: Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01)., Conclusion: Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA., (© 2023. The Author(s).)

Purpose: To evaluate biopsy-related complications and detection rates of any PCa and clinically significant PCa (csPCa, intended as grade group ≥ 2) between MRI-targeted TP fusion biopsies (TPBx) and TR ones (TRBx)., Methods: We performed a multicentric study on 4841 patients who underwent fusion biopsy between 2016 and 2023. A case-control matching was performed to find comparable cohorts of 646 TPBx and 646 TRBx. Mean T test and Pearson chi-square tests were used to compare continuous and categorical variables., Results: Baseline characteristics were comparable between the cohorts, except for target location with a higher rate of anterior lesions in TPBx group. Complications were rare and no difference was found between the groups, with similar rates of infections after TRBx and TPBx (N = 5 (0.8%) vs N = 2 (0.3%), p 0.45). All patients in TRBx and 90.1% in TPBx group received antibiotic prophylaxis. A higher csPCa detection rate was found in TPBx over the group (50.5% vs 36.2%, p < 0.001). On average, positive targeted cores were increased in TPBx group, for any PCa (1.6 vs 1.4, p 0.04) and csPCa (1.0 vs 0.8, p 0.02). Among the limitations of study, we acknowledge the retrospective design and the possible under-reporting of complications., Conclusions: MRI-targeted fusion TPBx achieves a significantly higher csPCa detection than TRBx, with a diagnostic advantage for apical and anterior lesions. No significant differences were found in terms of complications that were rare in both groups, considering a widespread adoption of antibiotic prophylaxis., (© 2024. The Author(s).)

Introduction : This study aimed to evaluate the added diagnostic value of systematic biopsies (SBx) after magnetic resonance imaging (MRI)-targeted biopsies (TBx) and the presence of prostate cancer (PCa) outside MRI targets, in a prospective, contemporary, multicentric series of fusion biopsy patients. Methods : We collected data on 962 consecutive patients who underwent fusion biopsy between 2022 and 2024. Prostate cancer was considered clinically significant (csPCa) in the case of grade ≥ 2. Median test and Fisher exact chi-square tests were used. To identify predictors of out-field positivity, univariate and multivariable logistic regression analyses were performed. Results : Prostate cancer and csPCa were detected by TBx only in 56% and 50%, respectively, and by SBx only in 55% and 45%, respectively ( p < 0.001). Prostate cancer and csPCa were diagnosed by TBx in 100 (10%) and 82 (8%) SBx-negative cases and by SBx in 86 (9%) and 54 (6%) TBx-negative cases ( p < 0.001). Tumors outside MRI targets were found in 213 (33%) cases in the same lobe and 208 (32%) in the contralateral lobe, most of them being csPCa. Predictors of out-field contralateral PCa were positive DRE (HR 1.50, p 0.03), PSA density ≥ 0.15 (HR 2.20, p < 0.001), and PI-RADS score 5 (HR 2.04, p 0.01). Conclusions : Both TBx and SBx identify a non-negligible proportion of csPCa when the other modality is negative. SBx after TBx should always be considered given the risk of missing other csPCa foci within the prostate, especially in patients with positive DRE, PSA density ≥ 0.15, and PIRADS 5 lesions.

Background: High-risk prostate cancer (PCa) patients frequently experience recurrence and progression after radical prostatectomy (RP). Neoadjuvant androgen deprivation therapy (ADT) has not demonstrated a clear oncological benefit and is not currently recommended., Objective: The SUGAR trial is the first phase 2, randomised, controlled, multicentre, noncommercial, open-label study investigating single-agent perioperative darolutamide compared with the standard of care (ie, upfront RP, without neoadjuvant ADT)., Design, Setting, and Participants: SUGAR aims to randomise 240 men affected by nonmetastatic PCa, with the major eligibility criteria being International Society of Urological Pathology grade group ≥4, seminal vesicle invasion at magnetic resonance imaging and/or clinically node-positive disease. Patients in the experimental arm will undergo neoadjuvant darolutamide monotherapy, RP, and adjuvant darolutamide, completing 9 mo of treatment., Outcome Measurements and Statistical Analysis: The primary endpoint is noncurable recurrence-free survival, an innovative and clinically meaningful measure; the secondary endpoints encompass safety; recurrence-free, metastasis-free, and overall survival; pathological response; and quality of life. A predictive biomarker analysis will also be performed., Results and Limitations: Initial data suggest that intensified neoadjuvant treatment with androgen receptor signalling inhibitors (ARSIs) is associated with a sustained pathological response and may improve outcomes, via tumour downstaging and micrometastasis eradication. ARSI monotherapy could further enhance tolerability., Conclusions: SUGAR will provide efficacy and safety information on perioperative darolutamide monotherapy compared with upfront RP, in a contemporary high-risk PCa population undergoing surgery., Patient Summary: The on-going SUGAR clinical trial evaluates 9 mo of darolutamide treatment in addition to radical prostatectomy, in men affected by prostate cancer with specific high-risk characteristics. It investigates whether this hormonal treatment can lower the rates of noncurable recurrences, maintaining a favourable tolerability profile., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Salvage radical prostatectomy (sRP) yields poor functional outcomes and relatively high complication rates. Gleason score (GS) 6 prostate cancer (PCa) has genetic and clinical features showing little, if not absent, metastatic potential. However, the behavior of GS 6 PCa recurring after previous PCa treatment including radiotherapy and/or ablation has not been investigated., Objective: To evaluate the oncological outcomes of sRP for radio- and/or ablation-recurrent GS 6 PCa., Design, Setting, and Participants: Retrospective data of sRP for recurrent PCa after local nonsurgical treatment were collected from 14 tertiary referral centers from 2000 to 2021., Intervention: Prostate biopsy before sRP and sRP., Outcome Measurements and Statistical Analysis: A survival analysis was performed for pre-sRP biopsy and sRP-proven GS 6. Concordance between PCa at pre-sRP biopsy and sRP histology was assessed., Results and Limitations: We included GS 6 recurrent PCa at pre-sRP biopsy (n = 142) and at sRP (n = 50), as two cohorts. The majority had primary radiotherapy and/or brachytherapy (83.8% of GS 6 patients at pre-sRP biopsy; 78% of GS 6 patients at sRP) and whole-gland treatments (91% biopsy; 85.1% sRP). Biopsy GS 6 10-yr metastasis, cancer-specific survival (CSS), and overall survival (OS) were 79% (95% confidence interval [CI] 61-89%), 98% (95-99%), and 89% (78-95%), respectively. Upgrading at sRP was 69%, 35.5% had a pT3 stage, and 13.4% had positive nodes. The sRP GS 6 10-yr metastasis-free survival, CSS, and OS were 100%, 100%, and 90% (95% CI 58-98%) respectively; pT3 and pN1 disease were found in 12% and 0%, respectively. Overall complications, high-grade complications, and severe incontinence were experienced by >50%, >10%, and >15% of men, respectively (in both the biopsy and the sRP cohorts). Limitations include the retrospective nature of the study and absence of a centralized pathological review., Conclusions: GS 6 sRP-proven PCa recurring after nonsurgical primary treatment has almost no metastatic potential, while patients experience relevant morbidity of the procedure. However, a significant proportion of GS 6 cases at pre-sRP biopsy are upgraded at sRP. In the idea not to overtreat, efforts should be made to improve the diagnostic accuracy of pre-sRP biopsy., Patient Summary: We investigated the oncological results of salvage radical prostatectomy for recurrent prostate cancer of Gleason score (GS) 6 category. We found a very low malignant potential of GS 6 confirmed at salvage radical prostatectomy despite surgical complications being relatively high. Nonetheless, biopsy GS 6 was frequently upgraded and had less optimal oncological control. Overtreatment for recurrent GS 6 after nonsurgical first-line treatment should be avoided, and efforts should be made to increase the diagnostic accuracy of biopsies for recurrent disease., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Prehabilitation programs play a key role in optimizing patient experiences and outcomes after surgery. However, there are few data on robot-assisted radical prostatectomy, and prehabilitation programs may be challenging to launch and maintain over time for every patient. Here we report our 5-yr experience of an on-site prehabilitation program and its impact on patient and hospital outcomes. During the study period, we observed continuous improvements in the same-day discharge rate (from 0% to 26.4%), hospital stay (from 3 to 0.9. d), costs (-63%), days out of hospital within 30 d after surgery in our center, and in comparison to contemporary nationwide data. However, despite these advantages, maintenance and diffusion of this program could be challenging owing to the absence of incentive support and lack of human resources. This led us to develop two free-access mobile apps, available on the app stores for both patients and surgeons, that include checklists, remote monitoring, and multiple educational materials aimed at simplifying the widespread use of optimized perioperative pathways. PATIENT SUMMARY: We found that a prehabilitation program before surgery can help in optimizing patient outcomes after robot-assisted removal of the prostate. We translated this program into a mobile app available for every patient., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Transperineal mpMRI-targeted fusion prostate biopsies (TPFBx) are recommended for prostate cancer diagnosis, but little is known about their learning curve (LC), especially when performed under local anaesthesia (LA). We investigated how operators' and institutions' experience might affect biopsy results., Methods: Baseline, procedure and pathology data of consecutive TPFBx under LA were prospectively collected at two academic Institutions, from Sep 2016 to May 2019. Main inclusion criterion was a positive MRI. Endpoints were biopsy duration, clinically significant prostate cancer detection rate on targeted cores (csCDR-T), complications, pain and urinary function. Data were analysed per-centre and per-operator (with ≥ 50 procedures), comparing groups of consecutive patient, and subsequently through regression and CUSUM analyses. Learning curves were plotted using an adjusted lowess smoothing function., Results: We included 1014 patients, with 27.3% csCDR-T and a median duration was 15 min (IQR 12-18). A LC for biopsy duration was detected, with the steeper phase ending after around 50 procedures, in most operators. No reproducible evidence in favour of an impact of experience on csPCa detection was found at operator's level, whilst a possible gentle LC of limited clinical relevance emerged at Institutional level; complications, pain and IPSS variations were not related to operator experience., Conclusion: The implementation of TPFBx under LA was feasible, safe and efficient since early phases with a relatively short learning curve for procedure time., (© 2023. The Author(s).)

Salvage radical prostatectomy (sRP) is a potentially curative option for locally radiorecurrent prostate cancer (PCa) but is associated with significant morbidity. Therefore, the European Association of Urology (EAU) guidelines recommend restricting sRP to a favorable-prognosis group according to the EAU criteria, but these have been validated considering only biochemical recurrence (BCR). Our aim was to test these criteria in a large, multicenter, contemporary cohort. We retrospectively reviewed 1265 patients who underwent sRP at 14 referral centers (2000-2021), stratified by compliance with the EAU criteria. Our primary outcome was metastasis-free survival (MFS). We included 1030 men, of whom 221 (21.5%) fully met the EAU recommended criteria for sRP and 809 (78.5%) did not. The EAU-compliant group experienced more favorable pathological and functional outcomes (79% vs 63% wearing no pads at 1 yr; p < 0.001) and had significantly better MFS (90% vs 76% at 5 yr; p < 0.001), prostate-specific antigen-free survival (55% vs 38% at 5 yr; p < 0.001), and overall survival (89% vs 84% at 5 yr; p = 0.01). This was verified by Cox regression analysis for MFS (hazard ratio 1.84, 95% confidence interval 1.13-2.99; p = 0.01). We found that adherence to the EAU criteria is associated with a lower risk of BCR and, more importantly, of metastasis after surgery. PATIENT SUMMARY: We looked at outcomes of surgical removal of the prostate for prostate cancer recurrence after radiotherapy or other nonsurgical treatments according to whether or not patients met the European Association of Urology (EAU) criteria for this surgery. We found that men who did not meet the criteria had a higher risk of metastasis and their benefit from surgery might be significantly less than for patients who do meet the EUA criteria., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: PSA density and an elevated PI-RADS score are among the strongest predictors of prostate cancer (PCa) in a fusion biopsy. Positive family history, hypertension, diabetes, and obesity have also been associated with the risk of developing PCa. We aim to identify predictors of the prostate cancer detection rate (CDR) in a series of patients undergoing a fusion biopsy., Methods: We retrospectively evaluated 736 consecutive patients who underwent an elastic fusion biopsy from 2020 to 2022. Targeted biopsies (2-4 cores per MRI target) were followed by systematic mapping (10-12 cores). Clinically significant PCa (csPCa) was defined as ISUP score ≥ 2. Uni- and multi-variable logistic regression analyses were performed to identify predictors of CDR among age, body mass index (BMI), hypertension, diabetes, positive family history, PSA, a positive digital rectal examination (DRE), PSA density ≥ 0.15, previous negative biopsy status, PI-RADS score, and size of MRI lesion., Results: The median patients' age was 71 years, and median PSA was 6.6 ng/mL. A total of 20% of patients had a positive digital rectal examination. Suspicious lesions in mpMRI were scored as 3, 4, and 5 in 14.9%, 55.0%, and 17.5% of cases, respectively. The CDR was 63.2% for all cancers and 58.7% for csPCa. Only age (OR 1.04, p < 0.001), a positive DRE (OR 1.75, p = 0.04), PSA density (OR 2.68, p < 0.001), and elevated PI-RADS score (OR 4.02, p = 0.003) were significant predictors of the CDR in the multivariable analysis for overall PCa. The same associations were found for csPCa. The size of an MRI lesion was associated with the CDR only in uni-variable analysis (OR 1.07, p < 0.001). BMI, hypertension, diabetes, and a positive family history were not predictors of PCa., Conclusions: In a series of patients selected for a fusion biopsy, positive family history, hypertension, diabetes, or BMI are not predictors of PCa detection. PSA-density and PI-RADS score are confirmed to be strong predictors of the CDR.

Introduction: When performing targeted biopsy (TBx), the need to add systematic biopsies (SBx) is often debated. Aim of the study is to evaluate the added value of SBx in addition to TBx in terms of prostate cancer (PCa) detection rates (CDR), and to test the concordance between multiparametric magnetic resonance imaging (mpMRI) findings and fusion biopsy results in terms of cancer location., Methods: We performed a retrospective, multicentric study that gathered data on 1992 consecutive patients who underwent elastic fusion biopsy between 2011 and 2020. A standardized approach was used, with TBx (2-4 cores per target) followed by SBx (12-14 cores). We assessed CDR of TBx, of SBx, and TBx+SBx for all cancers and clinically significant PCa (csPCa), defined as ISUP score ≥2. CDR was evaluated according to radiological and clinical parameters, with a particular focus on PI-RADS 3 lesions. In a subgroup of 1254 patients we tested the discordance between mpMRI findings and fusion biopsy results in terms of cancer location. Uni- and multivariable logistic regression analyses were performed to identify predictors of CDR., Results: CDR of TBx+SBx was 63.0% for all cancers and 38.8% of csPCa. Per-patient analysis showed that SBx in addition to TBx improved CDR by 4.5% for all cancers and 3.4% for csPCa. Patients with lesions scored as PI-RADS 3, 4, and 5 were diagnosed with PCa in 27.9%, 72.8%, and 92.3%, and csPCa in 10.7%, 43.6%, and 69.3%, respectively. When positive, PI-RADS 3 lesions were ISUP grade 1 in 61.1% of cases. Per-lesion analysis showed that discordance between mpMRI and biopsy was found in 56.6% of cases, with 710 patients having positive SBx outside mpMRI targets, of which 414 (58.0%) were clinically significant. PSA density ≥0.15 was a strong predictor of CDR., Conclusions: The addition of systematic mapping to TBx contributes to a minority of per-patient diagnoses but detects a high number of PCa foci outside mpMRI targets, increasing biopsy accuracy for the assessment of cancer burden within the prostate. High PSA-density significantly increases the risk of PCa, both in the whole cohort and in PI-RADS 3 cases., (© 2022 Wiley Periodicals LLC.)

Introduction: Androgen deprivation therapy (ADT) is the key of medical treatment for advanced prostate cancer (PCa), especially in elderly patients. However, the adherence of ADT prescription to current guidelines is not optimal and must be balanced against possible side effects. Aim of this study was to evaluate the prescriptive appropriateness of ADT and ADT-related adverse events in a referral center for PCa., Methods: Five hundred fifty six patients who received an outpatient prescription for ADT from 2014 to 2018 were retrospectively identified from an administrative database. Only standard ADT was considered, including GnRH agonists, GnRH antagonists, and antiandrogens. Prescriptive appropriateness was defined according to the last European Association of Urology (EAU) guidelines. Our cohort was stratified according to age categories and patient follow-up was updated., Results: Four hundred twenty five patients were available for analysis. Mean age was 80 years; 96.3% of our patients fell in the "elderly" category. There was a predominance of GnRH agonists over the antagonists (84.9% vs 13%). 15.5% of ADTs did not have an appropriate indication according to guidelines. Patient compliance to ADT was evaluated as good in 372 (87.5%) cases. ADT-related complications were detected in 166 (39%) patients: bone, cardiovascular, and other complications were reported in 7.3%, 8.9%, and 19% of patients. Progression of disease was noted in 165 (38.8%) cases during ADT. At last follow-up, 124 (30.1%) patients were deceased., Conclusions: In a referral center, most ADT prescriptions followed EAU guidelines, but a non-negligible proportion still did not fall within these indications, exposing patients to unnecessary side effects. Compliance to ADT was generally good with a predominant use of GnRH agonists. Tolerance to ADT was fair, even if standardized reports were lacking.

Introduction: When performing a nerve-sparing (NS) robotic radical prostatectomy (RARP), cancer location based on multiparametric MRI (mpMRI) is essential, as well as the location of positive biopsy cores outside mpMRI targets. The aim of this pilot study was to assess the feasibility of intraoperative 3D-TRUS-mpMRI elastic fusion imaging to guide RARP and to evaluate its impact on the surgical strategy., Methods: We prospectively enrolled 11 patients with organ-confined mpMRI-visible prostate cancer (PCa), histologically confirmed at transperineal fusion biopsy using Koelis Trinity. Before surgery, the 3D model of the prostate generated at biopsy was updated, showing both mpMRI lesions and positive biopsy cores, and was displayed on the Da Vinci robotic console using TilePro™ function., Results: Intraoperative 3D modeling was feasible in all patients (median of 6 min). The use of 3D models led to a major change in surgical strategy in six cases (54%), allowing bilateral instead of monolateral NS, or monolateral NS instead of non-NS, to be performed. At pathologic examination, no positive surgical margins (PSMs) were reported. Bilateral PCa presence was detected in one (9%), four (36%), and nine (81%) patients after mpMRI, biopsy, and RARP, respectively. Extracapsular extension was found in two patients (18%) even if it was not suspected at MRI., Conclusions: Intraoperative 3D-TRUS-mpMRI modeling with Koelis Trinity is feasible and reliable, helping the surgeon to maximize functional outcomes without increasing the risk of positive surgical margins. The location of positive biopsy cores must be registered in 3D models, given the rates of bilateral involvement not seen at mpMRI.

Objective: To investigate the diagnostic accuracy of the PI-RADS v2.1 multiparametric magnetic resonance imaging (mpMRI) features in predicting extraprostatic extension (mEPE) of prostate cancer (PCa), as well as to develop and validate a comprehensive mpMRI-derived score (mEPE-score)., Methods: We retrospectively reviewed all consecutive patients admitted to two institutions for radical prostatectomy for PCa with available records of mpMRI performed between January 2015 and December 2020. Data from one institution was used for investigating diagnostic performance of each mEPE feature using radical prostatectomy specimens as benchmark. The results were implemented in a mEPE-score as follows: no mEPE features: 1; capsular abutment: 2; irregular or spiculated margin: 3; bulging prostatic contour, or asymmetry of the neurovascular bundles, or tumor-capsule interface > 1.0 cm: 4; ≥ 2 of the previous three parameters or measurable extraprostatic disease: 5. The performance of mEPE features was evaluated using the five diagnostic parameters and ROC curve analysis., Results: Two-hundred patients were enrolled at site 1 and 76 at site 2. mEPE features had poor sensitivities ranging from 0.08 (0.00-0.15) to 0.71 (0.59-0.83), whereas specificity ranged from 0.68 (0.58-0.79) to 1.00. mEPE-score showed excellent discriminating ability (AUC > 0.8) and sensitivity = 0.82 and specificity = 0.77 with a threshold of 3. mEPE-score had AUC comparable to ESUR-score (p = 0.59 internal validation; p = 0.82 external validation), higher than or comparable to mEPE-grade (p = 0.04 internal validation; p = 0.58 external validation), and higher than early-and-late-EPE (p < 0.0001 internal and external validation). There were no significant differences between readers having different expertise with EPE-score (p = 0.32) or mEPE-grade (p = 0.45), but there were significant differences for ESUR-score (p = 0.02) and early-versus-late-EPE (p = 0.03)., Conclusions: The individual mEPE features have low sensitivity and high specificity. The use of mEPE-score allows for consistent and reliable assessment for pathologic EPE., Key Points: • Individual PI-RADS v2.1 mpMRI features had poor sensitivities ranging from 0.08 (0.00-0.15) to 0.71 (0.59-0.83), whereas Sp ranged from 0.68 (0.58-0.79) to 1.00. • mEPE-score is an all-inclusive score for the assessment of pEPE with excellent discriminating ability (i.e., AUC > 0.8) and Se = 0.82, Sp = 0.77, PPV = 0.74, and NPV = 0.84 with a threshold of 3. • The diagnostic performance of the expert reader and beginner reader with pEPE-score was comparable (p = 0.32)., (© 2022. The Author(s).)

Purpose: To assess differences in referral and pathologic outcomes for uro-oncology cases prior to and during the COVID pandemic, comparing clinical and pathological data of cancer surgeries performed at an academic referral center between 2019 and 2020., Methods: We collected data of 880 prostate biopsies, 393 robot-assisted radical prostatectomies (RARP) for prostate cancer (PCa), 767 trans-urethral resections of bladder tumor (TURB) and 134 radical cystectomies (RC) for bladder cancer (BCa), 29 radical nephro-ureterectomies (RNU) for upper tract urothelial carcinoma, 130 partial nephrectomies (PN) and 12 radical nephrectomies (RN) for renal cancer, and 41 orchifunicolectomies for testicular cancer. Data of patients treated in 2019 (before COVID-19 pandemic) were compared to patients treated in 2020 (during pandemic)., Results: No significant decline in uro-oncological surgical activity was seen between 2019 and 2020. No significant increase in time between diagnosis and surgery was observed for all considered cancers. No differences in terms of main pathologic features were observed in patients undergoing RARP, TURB, RNU, RN/PN, or orchifunicolectomy. A higher proportion of ISUP grade 3 and 4 PCa were diagnosed in 2020 at biopsy (p = 0.001), but this did not translate into worse pathological grade/stage at RARP. In 2020, more advanced disease features were seen after RC, including lymph node involvement (p = 0.01) and non-organ confined disease (p = 0.02)., Conclusion: Neither decline in uro-oncologic activity nor delay between diagnosis and treatment was observed at our institution during the first year of COVID-19 pandemic. No significant worsening of cancer disease features was found in 2020 except for muscle-invasive BCa., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To build a machine learning (ML) model to detect extraprostatic extension (EPE) of prostate cancer (PCa), based on radiomics features extracted from prostate MRI index lesions., Methods: Consecutive MRI exams of patients undergoing radical prostatectomy for PCa were retrospectively collected from three institutions. Axial T2-weighted and apparent diffusion coefficient map images were annotated to obtain index lesion volumes of interest for radiomics feature extraction. Data from one institution was used for training, feature selection (using reproducibility, variance and pairwise correlation analyses, and a correlation-based subset evaluator), and tuning of a support vector machine (SVM) algorithm, with stratified 10-fold cross-validation. The model was tested on the two remaining institutions' data and compared with a baseline reference and expert radiologist assessment of EPE., Results: In total, 193 patients were included. From an initial dataset of 2436 features, 2287 were excluded due to either poor stability, low variance, or high collinearity. Among the remaining, 14 features were used to train the ML model, which reached an overall accuracy of 83% in the training set. In the two external test sets, the SVM achieved an accuracy of 79% and 74% respectively, not statistically different from that of the radiologist (81-83%, p = 0.39-1) and outperforming the baseline reference (p = 0.001-0.02)., Conclusions: A ML model solely based on radiomics features demonstrated high accuracy for EPE detection and good generalizability in a multicenter setting. Paired to qualitative EPE assessment, this approach could aid radiologists in this challenging task., Key Points: • Predicting the presence of EPE in prostate cancer patients is a challenging task for radiologists. • A support vector machine algorithm achieved high diagnostic accuracy for EPE detection, with good generalizability when tested on multiple external datasets. • The performance of the algorithm was not significantly different from that of an experienced radiologist., (© 2021. The Author(s).)

Background: Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP show improved results. Our objectives were to evaluate sRP oncological outcomes and predictors of positive margins and biochemical recurrence (BCR)., Methods: We retrospectively collected data of sRP for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers in United States, Australia and Europe, from 2000 to 2016. SM and BCR were evaluated in a univariate and multivariable analysis. Overall and cancer-specific survival were also assessed., Results: We included 414 cases, 63.5% of them performed after radiotherapy. Before sRP the majority of patients had biopsy Gleason score (GS) ≤7 (55.5%) and imaging negative or with prostatic bed involvement only (93.3%). Final pathology showed aggressive histology in 39.7% (GS ≥9 27.6%), with 52.9% having ≥pT3 disease and 16% pN+. SM was positive in 29.7%. Five years BCR-Free, cancer-specific survival and OS were 56.7%, 97.7% and 92.1%, respectively. On multivariable analysis pathological T (pT3a odds ratio [OR] 2.939, 95% confidence interval [CI] 1.469-5.879; ≥pT3b OR 2.428-95% CI 1.333-4.423) and N stage (pN1 OR 2.871, 95% CI 1.503-5.897) were independent predictors of positive margins. Pathological T stage ≥T3b (OR 2.348 95% CI 1.338-4.117) and GS (up to OR 7.183, 95% CI 1.906-27.068 for GS >8) were independent predictors for BCR. Limitations include the retrospective nature of the study and limited follow-up., Conclusions: In a contemporary series, sRP showed promising oncological control in the medium term despite aggressive pathological features. BCR risk increased in case of locally advanced disease and higher GS. Future studies are needed to confirm our findings., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To evaluate the premalignant potential of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP)., Methods: Patients diagnosed with monofocal HGPIN (mHGPIN), widespread HGPIN (≥4 cores, wHGPIN) and/or ASAP who underwent at least one rebiopsy during their follow-up, were enrolled. All enrollment biopsies underwent central pathologic revision. Risks for PCa were estimated using Fine and Gray method for competing risk., Results: Pathologic revision changed the original diagnosis in 32.3% of cases. Among 336 cases enrolled, PCa was diagnosed in 164 (48.8%), and more specifically in 20 (30.3%) mHGPIN, 10 (34.5%) wHGPIN, 101 (54.0%) ASAP, and 33 (61.1%) HGPIN + ASAP (mean follow-up 124 months). Most PCa were Gleason score 6(3 + 3) (51.0%) and 7(3 + 4) (34.3%). On multivariate analysis, HGPIN + ASAP (HR 2.76, p  < 0.001) and ASAP alone (HR 2.41, p  < 0.001) were the only lesions significantly associated with PCa development. Of all cancers detected, 64.3% were at first rebiopsy. A rebiopsy performed within 3 months after ASAP diagnosis had a 45% chance of finding PCa. At Kaplan-Meier survival curves, median PCa-free survival was 48.1 months for HGPIN + ASAP and 64.9 months for ASAP ( p 0.0005 at Log-rank test). At 1 year, 70% of HGPIN + ASAP, 73% of ASAP, 89% of wHGPIN, and 84% of mHGPIN were PCa-free., Conclusion: The diagnosis of ASAP and HGPIN strongly relies on the expertise of dedicated uro-pathologists. Finding of ASAP is a strong risk factor for a subsequent PCa diagnosis, advising a rebiopsy, possibly within 3 months. m/wHGPIN should not be routinely rebiopsied.

Objectives: To externally validate the currently available nomograms for predicting lymph node invasion (LNI) in patients with prostate cancer (PCa) and to assess the potential risk of complications of extended pelvic lymph node dissection (ePLND) when using the recommended threshold., Methods: A total of 14 921 patients, who underwent radical prostatectomy with ePLND at eight European tertiary referral centres, were retrospectively identified. After exclusion of patients with incomplete biopsy or pathological data, 12 009 were included. Of these, 609 had undergone multiparametic magnetic resonance imaging-targeted biopsies. Among ePLND-related complications we included lymphocele, lymphoedema, haemorrhage, infection and sepsis. The performances of the Memorial Sloan Kettering Cancer Centre (MSKCC), Briganti 2012, Briganti 2017, Briganti 2019, Partin 2016 and Yale models were evaluated using receiver-operating characteristic curve analysis (area under the curve [AUC]), calibration plots, and decision-curve analysis., Results: Overall, 1158 patients (9.6%) had LNI, with a mean of 17.7 and 3.2 resected and positive nodes, respectively. No significant differences in AUCs were observed between the MSKCC (0.79), Briganti 2012 (0.79), Partin 2016 (0.78), Yale (0.80), Briganti 2017 (0.81) and Briganti 2019 (0.76) models. A direct comparison of older models showed that better discrimination was achieved with the MSKCC and Briganti 2012 nomograms. A tendency for underestimation was seen for all the older models, whereas the Briganti 2017 and 2019 nomograms tended to overestimate LNI risk. Decision-curve analysis showed a net benefit for all models, with a lower net benefit for the Partin 2016 and Briganti 2019 models. ePLND-related complications were experienced by 1027 patients (8.9%), and 12.6% of patients with pN1 disease., Conclusions: The currently available nomograms have similar performances and limitations in the prediction of LNI. Miscalibration was present, however, for all nomograms showing a net benefit. In patients with only systematic biopsy, the MSKCC and Briganti 2012 nomograms were superior in the prediction of LNI., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Objective: To assess the outcomes of multiparametric magnetic resonance imaging (mpMRI) transperineal targeted fusion biopsy (TPFBx) under local anaesthesia., Patients and Methods: We prospectively screened 1327 patients with a positive mpMRI undergoing TPFBx (targeted cores and systematic cores) under local anaesthesia, at two tertiary referral institutions, between September 2016 and May 2019, for inclusion in the present study. Primary outcomes were detection of clinically significant prostate cancer (csPCa) defined as (1) International Society of Urological Pathologists (ISUP) grade >1 or ISUP grade 1 with >50% involvement of prostate cancer (PCa) in a single core or in >2 cores (D1) and (2) ISUP grade >1 PCa (D2). Secondary outcomes were: assessment of peri-procedural pain (numerical rating scale [NRS]) and procedure timings; erectile (International Index of Erectile Function) and urinary (International Prostate Symptom Score) function changes; and complications. We also investigated the value of systematic sampling and concordance with radical prostatectomy (RP)., Results: A total of 1014 patients were included, of whom csPCa was diagnosed in 39.4% (n = 400). The procedure was tolerable (NRS pain score 3.1 ± 2.3), with no impact on erectile (P = 0.45) or urinary (P = 0.58) function, and a low rate of complications (Clavien-Dindo grades 1 or 2, n = 8; grade >2, n = 0). No post-biopsy sepsis was recorded. Twenty-two men (95% confidence interval [CI] 17-29) needed to undergo additional systematic biopsy to diagnose one csPCa missed by targeted biopsies (D1). ISUP grade concordance of biopsies with RP was as follows: k = 0.40 (95% CI 0.31-0.49) for targeted cores alone and k = 0.65 (95% CI 0.57-0.72; P < 0.05) overall., Conclusions: The use of TPFBx under local anaesthesia yielded good csPCa detection and was feasible, quick, well tolerated and safe. Infectious risk was negligible. Addition of systematic to targeted cores may not be needed in all men, although it improves csPCa detection and concordance with RP., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Purpose: Several transperineal biopsy series have proven feasibility under local anesthesia. However, there is a lack of large analyses detailing pain outcomes and factors influencing pain., Materials and Methods: From 2016 to 2019 we performed a multicenter prospective study in men undergoing multiparametric magnetic resonance imaging-transperineal fusion biopsies (target+systematic cores) under local anesthesia. Primary outcomes were 1) pain scores (assessed through a 0 to 10-point numeric rating scale) and 2) identification of factors associated with severe pain. The secondary outcome was to evaluate pain influence on clinically significant prostate cancer target cores detection., Results: We included 1,008 men undergoing transperineal fusion biopsies under local anesthesia. Mean±SD numeric rating scale pain scores were 3.9±2.1 at local anesthesia administration and 3.1±2.3 when performing biopsies. Pain was not associated with lower clinically significant prostate cancer detection on targeted cores (p=0.23 and p=0.47 depending on clinically significant prostate cancer definition). On multivariate analysis age (OR 0.96, 95% CI 0.94-0.99) and severe anxiety (OR 2.99, 95% CI 1.83-4.89) were a protective and risk factor, respectively, for severe biopsy pain. Procedural time was also associated with an increased risk of experiencing severe biopsy pain (OR 1.04, 95% CI 1.00-1.08). If aiming to test the possible effects of anxiety preventive measures on pain, an anxiety cutoff greater than 6 on a numeric rating scale would decrease to 13% the number of patients being treated while identifying 56% of those experiencing severe pain., Conclusions: Transperineal fusion biopsies under local anesthesia result in moderate pain. Pain does not influence clinically significant prostate cancer target detection. Patient anxiety predicts pain. A numeric rating scale based anxiety assessment may be used to identify those at higher risk for experiencing severe pain in men undergoing transperineal fusion biopsies.

Objective: To evaluate machine learning-based classifiers in detecting clinically significant prostate cancer (PCa) with Prostate Imaging Reporting and Data System (PI-RADS) score 3 lesions., Methods: We retrospectively enrolled 346 patients with PI-RADS 3 lesions at two institutions. All patients underwent prostate multiparameter MRI (mpMRI) and transperineal MRI-ultrasonography (MRI-US)-targeted biopsy. We collected data on age, pre-biopsy serum prostate-specific antigen (PSA) level, prostate volume (PV), PSA density (PSAD), the location of suspicious PI-RADS 3 lesions, and histopathology results. Four machine learning-based classifiers-logistic regression, support vector machine, eXtreme Gradient Boosting (XGBoost), and random forest-were trained using datasets from Nanjing Drum Tower Hospital. External validation was carried out using datasets from Molinette Hospital., Results: Among 287 PI-RADS 3 patients, prostate cancer was proven pathologically in 59 (20.6%), and 228 (79.4%) had benign lesions. For 380 PI-RADS 3 lesions, 81 (21.3%) were proven to be PCa and 299 (78.7%) benign. Among four classifiers, the random forest classifier had the best performance in both patient-based and lesion-based datasets, with overall accuracy of 0.713 and 0.860, sensitivity of 0.857 and 0.613, and area under curve (AUC) of 0.771 and 0.832, respectively. In external validation, our best classifiers had an AUC of 0.688 with the best sensitivity (0.870) and specificity (0.500) in the 59 PI-RADS 3 patients in Molinette Hospital dataset., Conclusions: The machine learning-based random forest classifier provided a reliable probability if a PI-RADS 3 patient was benign., Key Points: • Machine learning-based classifiers could combine the clinical characteristics with accessible information on image report of PI-RADS 3 patient to generate a probability of malignancy. • This probability could assist surgeons to make diagnostic decisions with more confidence and higher efficiency.

Objective: To evaluate the feasibility of "in-office" TPFBx under local anesthesia (LA)., Materials and Methods: We prospectively screened for eligibility data of 724 consecutive men undergoing either TPFBx (target and systematic cores) or TPSBx (systematic cores only) from September 2016 to June 2018 due to suspicion of prostate cancer (CaP), according to predefined exclusion criteria., Results: We included 459 men (TPFBx n = 279 including n = 338 mpMRI lesions, Pi-RADS 4 in 63.6%; TPSBx n = 180). Median procedural time and maximum pain were 19 minutes and 5 numeric rating scale (NRS) points; pain was highest at the time of LA. Only 1 major complication occurred (Clavien 3a). Hematuria and hematospermia were frequent (72.6% and 54.2%). Vaso-vagal reactions and AUR were rare (0.7% and 0.4%). No cases of UTI and 1 case of fever were recorded. No significant changes in erectile and urinary functions were noted from baseline compared to 40 days after TPFBx (P = .86 and P = .89). In comparison with TPSBx the sole differences were pain during prostatic sampling (P = .03), duration of hematospermia (P <.0001) and procedural time (P <.001) all higher for TPFBx. Clinically significant (cs) CaP was detected in n = 150 (53.8%) patients in the TPFBx group (34.9%, 51.7%, and 75% of Pirads 3, 4, and 5, respectively). Addition of systematic cores detected n = 25 csCaP that were missed by targeted cores (17.4% of all csCaP)., Conclusion: TPFBx under LA are feasible, yielding high tolerability, low complications, no impact on erectile and urinary function and good csCaP detection. Addition of systematic to targeted cores remains recommended. Further studies are needed to confirm our findings., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Salvage radical prostatectomy (sRP) represents a curative option for prostate cancer (PCa) biochemical recurrence (BCR) after radiation therapy (RT). In this review, we aimed to outline the contemporary results and use of sRP., Methods: A web search was performed on the Ovid platform using Embase and Medline databases from January 2010 using pre-defined search terms. Web search was implemented by manual search. Oncological and functional outcomes and complications were summarized using standard classification systems, when feasible., Results: sRP is currently underused, being chosen for radio-recurrent PCa treatment in around 1% of the cases. Surgery is complex due to radiation-induced tissue changes making posterior planes and apex dissection particularly challenging. Patient selection is paramount to maximize the oncological benefit. Most series report a BCR-free survival > 60%, mainly at the end of a short- to intermediate-term follow-up. Five-year progression-free survival is nearly 50% and 5-year cancer-specific survival rates are around 90%. Major peri-operative complications, anastomotic leaks and strictures, still more frequent than in a primary RP setting, have been steering towards more acceptable rates in recent years, when compared to historical series. Continence rates are widely variable, often in between 39 and 60%. Potency remains difficult to recover., Conclusions: sRP represents a curative option with promising short- to medium-term oncological results and acceptable side effects, in high-volume institutions. In appropriately selected patients, the procedure should not be underused due to the fear of poor functional outcomes and/or complications. Prospective studies are needed to assess the long-term outcomes and to further refine patient selection criteria.

Purpose: To study the detection of clinically significant prostate cancer (PCa) by readers with different experience, comparing performance with biparametric magnetic resonance imaging (bmMRI) and with the reference multiparametric (mpMRI)., Methods: Retrospective analysis of 68 patients with mpMRI of the prostate at 1.5 Tesla using a 32 phased-array coil. Forty-five patients (cases) underwent radical prostatectomy, whereas 23 (controls) had a negative prostate biopsy and ≥ 2.5 years of negative follow-up. Six observers (two with 1000 cases interpreted, two with 300, two with 100) performed the analysis first with bpMRI including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps and T2-weighted (T2W) imaging in three planes and, after 1 month, with mpMRI, adding dynamic contrast enhancement (DCE). The performance was quantified by sensitivity (SNS), specificity (SPC) and area under the curve (AUC) of the ROC (Receiver Operating Characteristics) procedure., Results: Concordance within observers of equivalent experience was good (weighted Cohen's k ≈ 0.7). The two expert readers performed as well in bpMRI as in mpMRI (SNS = 0.91-0.96, AUC = 0.86-0.93; p ≥ 0.10); readers with 300 cases performed well in mpMRI, but significantly worse in bpMR: SNS = 0.58 versus 0.91 (p < 0.0001) and AUC = 0.73 versus 0.86 (p = 0.01); the limited experience of readers with 100 cases showed in mpMRI (SNS = 0.71; AUC = 0.77) and even more in bpMRI (SNS = 0.50; AUC = 0.68)., Conclusion: The study revealed the impact of the readers' experience when using bpMRI. The bpMRI without contrast media was a valid alternative for expert readers, whereas less experienced ones needed DCE to significantly boost SNS and AUC. Results indicate 700-800 cases as threshold for reliable interpretation with bpMRI.