Retzius-sparing versus standard robot-assisted laparoscopic prostatectomy: A two-year patient-reported and oncological assessment.

PURPOSE: To evaluate the two-year functional and oncological outcomes of Retzius-sparing robot-assisted laparoscopic prostatectomy (rsRALP) and standard approach (sRALP). METHODS: A total of 200 consecutive patients who underwent either sRALP (n = 100) or rsRALP (n = 100) for clinically localized PCa at a single referral European center between 2015 and 2020 were identified from a prospectively cohort, as part of the Belgian Cancer Registry. Primary outcomes included functional outcomes and quality of life (QoL) using validated patient-reported outcome measures (PROMs) assessed at 1-, 3-, 12-, and 24-months post-surgery. Secondary outcomes comprised oncological outcomes reported as positive surgical margins (PSM) and 5-year biochemical recurrence (BCR). Kaplan-Meier analysis with log-rank test and multivariable Cox regression were used. RESULTS: The median follow-up was 60 months. No significant differences were observed between the surgical approaches in terms of patient and tumor characteristics. Urinary function and QoL were significantly better at each follow-up period (all p ≤ 0.01) with rsRALP, while sexual function was not significantly different 12 months after surgery. No significant difference in positive surgical margins rate was observed between surgical approaches (31% vs 32%, p = 0.9). Retzius-sparing RALP was associated with longer PSM lengths (5 mm vs 2.5 mm, p = 0.02), a higher multifocality rate (34% vs. 13%, p < 0.001), more occurrences in organ-confined disease (59% vs. 39%, p < 0.001) and at anterior locations (37% vs. 16%, p = 0.05). Five-year BCR-free survival was not significantly different, and surgical approach was not a predictor of BCR. CONCLUSIONS: The rsRALP approach significantly improves both early and short-term urinary function and QoL compared to sRALP. Despite being associated with worse PSM characteristics, no significant decrease in BCR-free survival was observed with rsRALP.

Magnetic resonance imaging targeted biopsy in biopsy-naïve patients and the risk of overtreatment in prostate cancer: a grading issue.

OBJECTIVE: To evaluate the impact of applying the 2014 and 2019 International Society of Urological Pathology (ISUP) recommendations on grade group distribution and concordance with radical prostatectomy (RP). MATERIALS AND METHODS: Overall, 655 biopsy-naïve patients diagnosed by magnetic resonance imaging (MRI) targeted and systematic biopsies for Prostate Imaging Reporting and Data System score ≥3 lesions were identified from a prospectively maintained database from 2016 and 2022. Clinically significant prostate cancer was detected in 249 patients, of whom 69 underwent RP. Wilcoxon signed rank and McNemar's tests were used to compare the ISUP grade group distribution and concordance with RP after applying the 2014 (i.e., highest grade) and 2019 (i.e., global grade) ISUP recommendations, respectively. RESULTS: Compared to the 2014 ISUP recommendations, the 2019 ISUP recommendations were associated with a significant decrease in ISUP Grade Group 4 (range of difference from -13% to -5%) and an increase in ISUP Grade Group 2 (range of difference from +6% to +11%) in MRI targeted biopsy only, MRI targeted with perilesional biopsies, and MRI targeted with systematic biopsies (all P < 0.01). In patients who underwent RP, a significant decrease in downgrading was observed with all biopsy strategies (range of difference from -19% to -12%; P ≤ 0.008), along with an increase in concordance with RP specimen (range of difference from +12% to +13%; P ≤ 0.02). The use of the 2019 ISUP recommendation was associated with RP specimen a lower treatment burden. CONCLUSIONS: The use of the 2019 ISUP recommendations mitigates the grade migration induced by MRI targeted biopsy and improves the concordance with the final RP specimen.

Targeted microwave ablation for prostate cancer (FOSTINE1b): a prospective 'ablate-and-resect' study.

OBJECTIVE: 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 METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Active surveillance for low-risk prostate cancer with high tumor burden at biopsy: lessons learned from a contemporary radical prostatectomy cohort.

INTRODUCTION: To investigate whether initial tumor burden at biopsy could predict adverse features after radical prostatectomy (RP) in International Society of Urological Pathology (ISUP) 1 prostate cancer (PCa) patients. METHODS: This retrospective study was conducted in six referral centers. The cohort included patients with ISUP 1 PCa at systematic and MRI-targeted biopsy. We defined a high tumor burden at biopsy if ≥ 20% of cores were positive. The endpoint of the study was adverse features at RP, defined as ≥ pT3a stage and/or N1 and/or ISUP ≥ 3. Sensitivity analyses were performed to assess associations between different thresholds on biopsy (percentage of positive cores [PPC] ≥ 25%, ≥ 33%, ≥ 50%, bilateral positivity and positive cores > 3) and adverse features. As the number of targeted biopsies sampled may influence the number of positive cores, we used a virtual biopsy model in which all targeted biopsy results were interpreted as a single targeted biopsy. RESULTS: A total of 312 contemporary patients were included. At final pathology, 99 patients (32%) had adverse features. In multivariate logistic regression analysis, there was no statistical association between PPC > 20% and adverse features (OR = 1.22; 95%CI:0.69-2.22, p = 0.5). In sensitivity analysis, tumor burden at biopsy was not associated with the risk of adverse features, regardless of the definition used (all p > 0.05). When we considered a unique virtual targeted biopsy, tumor burden remained not associated with adverse features (all p > 0.05). CONCLUSIONS: ISUP 1 PCa tumor burden at biopsy did not predict adverse features in this study, suggesting that it should not be used alone as an exclusion criterion when assessing eligibility for active surveillance.

Predicting contralateral extraprostatic extension in unilateral high-risk prostate cancer: a multicentric external validation study.

PURPOSE: Accurate prediction of extraprostatic extension (EPE) is crucial for decision-making in radical prostatectomy (RP), especially in nerve-sparing strategies. Martini et al. introduced a three-tier algorithm for predicting contralateral EPE in unilateral high-risk prostate cancer (PCa). The aim of the study is to externally validate this model in a multicentric European cohort of patients. METHODS: The data from 208 unilateral high-risk PCa patients diagnosed through magnetic resonance imaging (MRI)-targeted and systematic biopsies, treated with RP between January 2016 and November 2021 at eight referral centers were collected. The evaluation of model performance involved measures such as discrimination (AUC), calibration, and decision-curve analysis (DCA) following TRIPOD guidelines. In addition, a comparison was made with two established multivariable logistic regression models predicting the risk of side specific EPE for assessment purposes. RESULTS: Overall, 38%, 48%, and 14% of patients were categorized as low, intermediate, and high-risk groups according to Martini et al.'s model, respectively. At final pathology, EPE on the contralateral prostatic lobe occurred in 6.3%, 12%, and 34% of patients in the respective risk groups. The algorithm demonstrated acceptable discrimination (AUC 0.68), comparable to other multivariable logistic regression models (p = 0.3), adequate calibration and the highest net benefit in DCA. The limitations include the modest sample size, retrospective design, and lack of central revision. CONCLUSION: Our findings endorse the algorithm's commendable performance, supporting its utility in guiding treatment decisions for unilateral high-risk PCa patients.

Transrectal versus transperineal prostate fusion biopsy: a pair-matched analysis to evaluate accuracy and complications.

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.

External validation and comparison of magnetic resonance imaging-based risk prediction models for prostate biopsy stratification.

PURPOSE: Magnetic resonance imaging (MRI) is a promising tool for risk assessment, potentially reducing the burden of unnecessary prostate biopsies. Risk prediction models that incorporate MRI data have gained attention, but their external validation and comparison are essential for guiding clinical practice. The aim is to externally validate and compare risk prediction models for the diagnosis of clinically significant prostate cancer (csPCa). METHODS: A cohort of 4606 patients across fifteen European tertiary referral centers were identified from a prospective maintained database between January 2016 and April 2023. Transrectal or transperineal image-fusion MRI-targeted and systematic biopsies for PI-RADS score of ≥ 3 or ≥ 2 depending on patient characteristics and physician preferences. Probabilities for csPCa, defined as International Society of Urological Pathology (ISUP) grade ≥ 2, were calculated for each patients using eight models. Performance was characterized by area under the receiver operating characteristic curve (AUC), calibration, and net benefit. Subgroup analyses were performed across various clinically relevant subgroups. RESULTS: Overall, csPCa was detected in 2154 (47%) patients. The models exhibited satisfactory performance, demonstrating good discrimination (AUC ranging from 0.75 to 0.78, p < 0.001), adequate calibration, and high net benefit. The model described by Alberts showed the highest clinical utility for threshold probabilities between 10 and 20%. Subgroup analyses highlighted variations in models' performance, particularly when stratified according to PSA level, biopsy technique and PI-RADS version. CONCLUSIONS: We report a comprehensive external validation of risk prediction models for csPCa diagnosis in patients who underwent MRI-targeted and systematic biopsies. The model by Alberts demonstrated superior clinical utility and should be favored when determining the need for a prostate biopsy.

The impact of prostate volume estimation on the risk-adapted biopsy decision based on prostate-specific antigen density and magnetic resonance imaging score.

PURPOSE: Utility of prostate-specific antigen density (PSAd) for risk-stratification to avoid unnecessary biopsy remains unclear due to the lack of standardization of prostate volume estimation. We evaluated the impact of ellipsoidal formula using multiparametric magnetic resonance (MRI) and semi-automated segmentation using tridimensional ultrasound (3D-US) on prostate volume and PSAd estimations as well as the distribution of patients in a risk-adapted table of clinically significant prostate cancer (csPCa). METHODS: In a prospectively maintained database of 4841 patients who underwent MRI-targeted and systematic biopsies, 971 met inclusions criteria. Correlation of volume estimation was assessed by Kendall's correlation coefficient and graphically represented by scatter and Bland-Altman plots. Distribution of csPCa was presented using the Schoots risk-adapted table based on PSAd and PI-RADS score. The model was evaluated using discrimination, calibration plots and decision curve analysis (DCA). RESULTS: Median prostate volume estimation using 3D-US was higher compared to MRI (49cc[IQR 37-68] vs 47cc[IQR 35-66], p < 0.001). Significant correlation between imaging modalities was observed (τ = 0.73[CI 0.7-0.75], p < 0.001). Bland-Altman plot emphasizes the differences in prostate volume estimation. Using the Schoots risk-adapted table, a high risk of csPCa was observed in PI-RADS 2 combined with high PSAd, and in all PI-RADS 4-5. The risk of csPCa was proportional to the PSAd for PI-RADS 3 patients. Good accuracy (AUC of 0.69 and 0.68 using 3D-US and MRI, respectively), adequate calibration and a higher net benefit when using 3D-US for probability thresholds above 25% on DCA. CONCLUSIONS: Prostate volume estimation with semi-automated segmentation using 3D-US should be preferred to the ellipsoidal formula (MRI) when evaluating PSAd and the risk of csPCa.

External validation of biochemical recurrence definition to predict oncologic outcomes following focal therapy for localized prostate cancer using high intensity focused ultrasound.

PURPOSE: This is an external validation of several biochemical recurrence definitions based on prostate specific antigen criteria (PSA). The purpose is to predict the need of additional treatment and failure after focal therapy using high intensity focused ultrasound (HIFU) for localized prostate cancer (PCa). MATERIALS AND METHODS: A total of 343 consecutive patients who underwent HIFU with Ablatherm® and Focal One® devices between June 2001 and November 2020 were identified. Treatment failure was defined as clinically significant PCa on postoperative biopsy, the need for salvage radical or systematic treatment, metastasis, or PCa-related death. The biochemical recurrence definitions tested were PSA nadir, time to PSA nadir, percentage of PSA reduction, Huber et al. criteria defined as PSA nadir + 1 ng/mL at 12 months or PSA nadir + 1.5 ng/mL at 24-36 months. Multivariable Cox regression analysis and decision-curve analysis were used to validate and compare criteria. Kaplan-Meier analysis was used to assess criteria associated with the highest accuracy. RESULTS: One hundred seventy-eight patients met the inclusion criteria and were analyzed. Overall, 61 (34%) and 41 (23%) patients had an additional treatment and failure with a median follow-up of 52 months. At multivariable analysis, model including Huber et al. criteria exhibited the highest Harrell's C-index for the prediction of the need of additional treatment (hazard ratio [HR]: 10, p < 0.001, c-index: 84%) and treatment failure (HR: 9.1, p < 0.001, c-index: 82%) as well as higher net benefit. The 60-months need of additional treatment and treatment failure-free survival were 89% and 98% compared to 26% and 49%, respectively, when stratified according to Huber et al. criteria (Log-rank test, p < 0.001). Similar results were found after excluding patient with non-clinically significant PCa at initial biopsy. CONCLUSIONS: We report an external validation of biochemical recurrence definitions predicting the need of additional treatment and failure after focal therapy using HIFU for localized PCa. Huber et al. criteria were identified as the most accurate and could be used to guide clinicians toward further evaluation and salvage treatments.

Risk stratification for early biochemical recurrence of prostate cancer in the era of multiparametric magnetic resonance imagining-targeted biopsy.

BACKGROUND: Multiparametric magnetic resonance imaging (MRI) and MRI-targeted biopsy are nowadays recommended in the prostate cancer (PCa) diagnostic pathway. Ploussard and Mazzone have integrated these tools into novel risk classification systems predicting the risk of early biochemical recurrence (eBCR) in PCa patients who underwent radical prostatectomy (RP). We aimed to assess available risk classification systems and to define the best-performing. METHODS: Data on 1371 patients diagnosed by MRI-targeted biopsy and treated by RP between 2014 and 2022 at eight European tertiary referral centers were analyzed. Risk classifications systems included were the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) risk groups, the Cancer of the Prostate Risk Assessment (CAPRA) score, the International Staging Collaboration for Cancer of the Prostate (STAR-CAP) classification, the Ploussard and Mazzone models, and ISUP grade group. Kaplan-Meier analyses were used to compare eBCR among risk classification systems. Performance was assessed in terms of discrimination quantified using Harrell's c-index, calibration, and decision curve analysis (DCA). RESULTS: Overall, 152 (11%) patients had eBCR at a median follow-up of 31 months (interquartile range: 19-45). The 3-year eBCR-free survival rate was 91% (95% confidence interval [CI]: 89-93). For each risk classification system, a significant difference among survival probabilities was observed (log-rank test p < 0.05) except for NCCN classification (p = 0.06). The highest discrimination was obtained with the STAR-CAP classification (c-index 66%) compared to CAPRA score (63% vs. 66%, p = 0.2), ISUP grade group (62% vs. 66, p = 0.07), Ploussard (61% vs. 66%, p = 0.003) and Mazzone models (59% vs. 66%, p = 0.02), and EAU (57% vs. 66%, p < 0.001) and NCCN (57% vs. 66%, p < 0.001) risk groups. Risk classification systems demonstrated good calibration characteristics. At DCA, the CAPRA score showed the highest net benefit at a probability threshold of 9%-15%. CONCLUSIONS: The performance of risk classification systems using MRI and MRI-targeted information was less optimistic when tested in a contemporary set of patients. CAPRA score and STAR-CAP classification were the best-performing and should be preferred for treatment decision-making.

Accuracy of elastic fusion biopsy: Comparing prostate cancer detection between targeted and systematic biopsy.

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.

Teaching robotic cystectomy: prospective pilot clinical validation of the ERUS training curriculum.

OBJECTIVE: To provide the first clinical validation of the European Association of Urology Robotic Urology Section (ERUS) curriculum for training in robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC). PATIENTS AND METHODS: The ERUS proposed a structured curriculum, divided into 11 steps, to train novice surgeons and help overcome the steep learning curve associated with iRARC. In this study, one trainee completed the curriculum under the mentorship of an expert. Twenty-one patients were operated on by the trainee following the proposed iRARC curriculum [(t)iRARC group] and were compared with 42 patients treated with the standard of care by the mentor [(m)iRARC group]. To evaluate curriculum safety, peri-operative outcomes, surgical margins and complications were assessed. Propensity-score matching (1:2) was used to identify comparable (t)iRARC and (m)iRARC cases. Matched variables included age, body mass index, neoadjuvant therapy, American Society of Anesthesiologists score and cT stage. Mann-Whitney and chi-squared tests were used to compare peri- and postoperative outcomes between the two cohorts. To evaluate curriculum efficacy, steps attempted and completed by the trainee were assessed and studied as a function of growing surgical experience of the trainee. RESULTS: The trainee progressed in proficiency-based training through steps of increasing difficulty. No differences in estimated blood loss, positive soft tissue margins, number of resected lymph nodes, overall and high-grade complications, or 90-day readmissions between the (t)iRARC and (m)iRARC groups were observed (all P > 0.05). However, operating time was significantly longer in the (t)iRARC group (P = 0.01). Of the 209 available steps, the trainee attempted 168 (80%) and successfully performed 125 (60%). Increasing experience was associated with more steps being successfully performed (P < 0.001). CONCLUSIONS: The proposed ERUS curriculum assists naïve surgeons during the learning curve for iRARC and should be encouraged in order to guarantee optimal outcomes during the learning phase of this procedure.

Optimizing multiparametric magnetic resonance imaging-targeted biopsy and detection of clinically significant prostate cancer: the role of core number and location.

PURPOSE: There is currently no consensus regarding the optimal number of multiparametric magnetic resonance imaging (MRI)-targeted biopsy (TB) cores and their spatial distribution within the MRI lesion. We aim to determine the number of TB cores and location needed to adequately detect csPCa. METHODS: We conducted a retrospective cohort study of 505 consecutive patients undergoing TB for positive MRI lesions defined by a PI-RADS score ≥ 3 between June 2016 and January 2022. Cores chronology and locations were prospectively recorded. The co-primary outcomes were the first core to detect clinically significant prostate cancer (csPCa) and the first highest ISUP grade group. The incremental benefit of each additional core was evaluated. Analysis was then performed by distinguishing central (cTB) and peripheral (pTB) within the MRI lesion. RESULTS: Overall, csPCa was detected in 37% of patients. To reach a csPCa detection rate of 95%, a 3-core strategy was required, except for patients with PI-RADS 5 lesions and those with PSA density ≥ 0.2 ng/ml/cc who benefited from a fourth TB core. At multivariable analysis, only a PSA density ≥ 0.2 ng/ml/cc was an independent predictive factor of having the highest ISUP grade group on the fourth TB cores (p = 0.03). No significant difference in the cancer detection rate was found between cTB and pTB (p = 0.9). Omitting pTB would miss 18% of all csPCa. CONCLUSION: A 3-core strategy should be considered for TB to optimize csPCa detection with additional cores needed for PI-RADS 5 lesions and high PSA density. Biopsy cores from both central and peripheral zones are required.

Optimizing multiparametric magnetic resonance imaging-targeted biopsy and prostate cancer grading accuracy.

PURPOSE: To assess the most efficient biopsy method to improve International Society of Urological Pathology (ISUP) grade group accuracy with final pathology of the radical prostatectomy (RP) specimen in the era of magnetic resonance imaging (MRI)-driven pathway. METHODS: A total of 753 patients diagnosed by transrectal MRI-targeted and systematic biopsies (namely "standard method"), treated by RP, between 2016 and 2021 were evaluated. Biopsy methods included MRI-targeted biopsy, side-specific systematic biopsies relative to index MRI lesion and combination of both. Number of MRI-targeted biopsy cores and positive cores needed per index MRI lesion were assessed. Multivariable analysis was performed to analyze predictive factors of upgrading using MRI targeted and ipsilateral systematic biopsies method. RESULTS: Overall, ISUP grade group accuracy varied among biopsy methods with upgrading rate of 35%, 49%, 27%, and 24% for MRI targeted, systematic, MRI targeted and ipsilateral systematic biopsies and standard methods, respectively (p < 0.001). A minimum of two positive MRI-targeted biopsies cores per index MRI lesion were required when testing MRI targeted and ipsilateral systematic biopsies method to reach equivalent accuracy compared to standard method. Omitting contralateral systematic biopsies spared an average of 5.9 cores per patient. At multivariable analysis, only the number of positive MRI-targeted biopsy cores per index MRI lesion was predictive of upgrading. CONCLUSION: MRI targeted and ipsilateral systematic biopsies allowed an accurate definition of ISUP grade group and appears to be an interesting alternative when compared with standard method, reducing total number of biopsy cores needed.

Expanding inclusion criteria for active surveillance in intermediate-risk prostate cancer: a machine learning approach.

PURPOSE: To develop new selection criteria for active surveillance (AS) in intermediate-risk (IR) prostate cancer (PCa) patients. METHODS: Retrospective study including patients from 14 referral centers who underwent pre-biopsy mpMRI, image-guided biopsies and radical prostatectomy. The cohort included biopsy-naive IR PCa patients who met the following inclusion criteria: Gleason Grade Group (GGG) 1-2, PSA < 20 ng/mL, and cT1-cT2 tumors. We relied on a recursive machine learning partitioning algorithm developed to predict adverse pathological features (i.e., ≥ pT3a and/or pN + and/or GGG ≥ 3). RESULTS: A total of 594 patients with IR PCa were included, of whom 220 (37%) had adverse features. PI-RADS score (weight:0.726), PSA density (weight:0.158), and clinical T stage (weight:0.116) were selected as the most informative risk factors to classify patients according to their risk of adverse features, leading to the creation of five risk clusters. The adverse feature rates for cluster #1 (PI-RADS ≤ 3 and PSA density < 0.15), cluster #2 (PI-RADS 4 and PSA density < 0.15), cluster #3 (PI-RADS 1-4 and PSA density ≥ 0.15), cluster #4 (normal DRE and PI-RADS 5), and cluster #5 (abnormal DRE and PI-RADS 5) were 11.8, 27.9, 37.3, 42.7, and 65.1%, respectively. Compared with the current inclusion criteria, extending the AS criteria to clusters #1 + #2 or #1 + #2 + #3 would increase the number of eligible patients (+ 60 and + 253%, respectively) without increasing the risk of adverse pathological features. CONCLUSIONS: The newly developed model has the potential to expand the number of patients eligible for AS without compromising oncologic outcomes. Prospective validation is warranted.

Pathological features of Prostate Imaging Reporting and Data System (PI-RADS) 3 MRI lesions in biopsy and radical prostatectomy specimens.

OBJECTIVE: To assess the whole pathology spectrum of Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified on magnetic resonance imaging, using systematic (SB), targeted biopsy (TB) and radical prostatectomy (RP) specimen analysis. METHODS: From a prospective database of patients undergoing RP after a combination of SB (median 12 cores) and fusion TB (median 3 cores), we included 150 PI-RADS 3 cases. Clinically significant prostate cancer (csPCa) was defined by a Grade Group 2 or more. The primary endpoints were unfavourable features in RP specimens. RESULTS: Targeted biopsy was negative in 20.7% of patients. Final Grade Group 3 or more and a pT3 stage was reported in 36.7% and 38.7% of RP specimens. The upgrading rate was 38.2% between biopsy and RP specimens. The concordance rate between Grade Group on TB and RP was only 38.0%. The two independent predictive factors for unfavourable disease (pT3-4 and/or final Grade Group 3-5) were prostate-specific antigen density (PSAD; P = 0.001) and presence of csPCa on TB (odds ratio 3.7; P = 0.001). The risk of unfavourable disease was increased 2.3-fold and 5.8-fold, respectively, for patients with a PSAD between 0.15 and 0.20, and a PSAD >0.20 ng/mL/g. The 5-year biochemical recurrence-free survival rate was 93.2%. CONCLUSIONS: PI-RADS 3 lesions exhibited aggressive features in almost 40% of cases. PSAD and presence of csPCa on TB are independent predictive factors for high-grade and/or extraprostatic disease. A combination of SB and TB improve grade prediction compared to use of TB alone.

Grade group 1 prostate cancer on biopsy: are we still missing aggressive disease in the era of image-directed therapy?

PURPOSE: Recently, Eggener et al. reignited a debate consisting to redefine Gleason Grade Group (GGG) 1 prostate cancer (PCa) as a precancerous lesion to reduce overdiagnosis and overtreatment. However, historical cohorts showed that some GGG1-labeled disease at biopsy may be underestimated by the standard PCa diagnostic workup. The aim was to assess whether the risk of adverse features at radical prostatectomy (RP) in selected GGG1 patients still exists in the era of pre-biopsy mpMRI and image-guided biopsies. METHODS: We retrospectively reviewed our data from a European RP dataset to assess in contemporary patients with GGG1 at mpMRI-targeted biopsy the rate of adverse features at final pathology, defined as ≥ pT3a and/or pN+ and/or GGG ≥ 3. RESULTS: A total of 419 patients with cT1-T2 cN0 GGG1-PCa were included. At final pathology, 143 (34.1%) patients had adverse features. In multivariate analysis, only unfavorable intermediate-risk/high-risk disease (defined on PSA or stage) was predictive of adverse features (OR 2.45, 95% CI 1.11-5.39, p = 0.02). A significant difference was observed in the 3-year biochemical recurrence-free survival between patients with and without adverse features (93.4 vs 87.8%, p = 0.026). In sensitivity analysis restricted low- and favorable intermediate-risk PCa, 122/383 patients (31.8%) had adverse features and no preoperative factors were statistically associated with this risk. CONCLUSION: In this European study, we showed that there is still a risk of underestimating GGG1 disease at biopsy despite the routine use of image-guided biopsies. Future studies are warranted to improve the detection of aggressive disease in GGG1-labeled patients by incorporating the latest tools such as genomic testing or radiomics.

[Prostate cancer, androgen deprivation, and risk of COVID-19 infection : A systematic review and meta-analysis]. / Cancer de Prostate, déprivation androgénique, et risques d'infection par la COVID-19 : revue systématique et méta-analyse.

INTRODUCTION: Male gender has been shown to be a risk factor for COVID-19 infection, and men are more likely to develop severe disease. The aim of this study was to evaluate the effect of androgen deprivation therapy (ADT) on the incidence of infection and severity of SARS-CoV-2 in prostate cancer patients. METHODS: A systematic review and meta-analysis were performed after searching PubMed, Scopus, and ClinicalTrial.org databases, between January 2020 and March 2022. Analyses were interpreted through forest plots for the following parameters: risk of infection, hospitalization, intensive care admission, and SARS-CoV-2-related death, with random or fixed-effects models. RESULTS: Fifteen articles were included in the systematic review and ten in the meta-analysis. Seven studies evaluated risk of infection in patients on ADT: OR=1.11 (95 % IC : [0.48-2.58] ; P=0.81). Six studies evaluated the risk of hospitalization in patients on ADT: TDA : OR=1.58 (95 % IC : [0.94-2.64] ; P=0.08). Seven studies evaluated risk of ICU admission in patients on ADT: OR=0.90 (95 % IC : [0.71-1.13] ; P=0.37). Nine studies evaluated mortality risk in patients on ADT: OR=1.07 (95 % IC : [0.61-1.87] ; P=0.82). CONCLUSION: ADT does not protect against SARS-CoV-2 in prostate cancer patients, nor does it protect against hospitalization, ICU admission, or mortality. These results remain questionable given the retrospective nature of the majority of studies included in our meta-analysis.

Indications for and complications of pelvic lymph node dissection in prostate cancer: accuracy of available nomograms for the prediction of lymph node invasion.

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.

Timing and delay of radical prostatectomy do not lead to adverse oncologic outcomes: results from a large European cohort at the times of COVID-19 pandemic.

PURPOSE: The current COVID-19 pandemic is transforming our urologic practice and most urologic societies recommend to defer any surgical treatment for prostate cancer (PCa) patients. It is unclear whether a delay between diagnosis and surgical management (i.e., surgical delay) may have a detrimental effect on oncologic outcomes of PCa patients. The aim of the study was to assess the impact of surgical delay on oncologic outcomes. METHODS: Data of 926 men undergoing radical prostatectomy across Europe for intermediate and high-risk PCa according to EAU classification were identified. Multivariable analysis using binary logistic regression and Cox proportional hazard model tested association between surgical delay and upgrading on final pathology, lymph-node invasion (LNI), pathological locally advanced disease (pT3-4 and/or pN1), need for adjuvant therapy, and biochemical recurrence. Kaplan-Meier analysis was used to estimate BCR-free survival after surgery as a function of surgical delay using a 3 month cut-off. RESULTS: Median follow-up and surgical delay were 26 months (IQR 10-40) and 3 months (IQR 2-5), respectively. We did not find any significant association between surgical delay and oncologic outcomes when adjusted to pre- and post-operative variables. The lack of such association was observed across EAU risk categories. CONCLUSION: Delay of several months did not appear to adversely impact oncologic results for intermediate and high-risk PCa, and support an attitude of deferring surgery in line with the current recommendation of urologic societies.