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.

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.

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.

Does Overgrading on Targeted Biopsy of Magnetic Resonance Imaging-visible Lesions in Prostate Cancer Lead to Overtreatment?

BACKGROUND AND OBJECTIVE: Targeted biopsy of the index prostate cancer (PCa) lesion on multiparametric magnetic resonance imaging (MRI) is effective in reducing the risk of overdiagnosis of indolent PCa. However, it remains to be determined whether MRI-targeted biopsy can lead to a stage shift via overgrading of the index lesion by focusing only on the highest-grade component, and to a subsequent risk of overtreatment. Our aim was to assess whether overgrading on MRI-targeted biopsy may lead to overtreatment, using radical prostatectomy (RP) specimens as the reference standard. METHODS: Patients with clinically localized PCa who had positive MRI findings (Prostate Imaging-Reporting and Data System [PI-RADS] score ≥3) and Gleason grade group (GG) ≥2 disease detected on MRI-targeted biopsy were retrospectively identified from a prospectively maintained database that records all RP procedures from eight referral centers. Biopsy grade was defined as the highest grade detected. Downgrading was defined as lower GG for the RP specimen than for MRI-targeted biopsy. Overtreatment was defined as downgrading to RP GG 1 for cases with GG ≥2 on biopsy, or to RP low-burden GG 2 for cases with GG ≥3 on biopsy. KEY FINDINGS AND LIMITATIONS: We included 1020 consecutive biopsy-naïve patients with GG ≥2 PCa on MRI-targeted biopsy in the study. Pathological analysis of RP specimens showed downgrading in 178 patients (17%). The transperineal biopsy route was significantly associated with a lower risk of downgrading (odds ratio 0.364, 95% confidence interval 0.142-0.814; p = 0.022). Among 555 patients with GG 2 on targeted biopsy, only 18 (3.2%) were downgraded to GG 1 on RP. Among 465 patients with GG ≥3 on targeted biopsy, three (0.6%) were downgraded to GG 1 and seven were downgraded to low-burden GG 2 on RP. The overall risk of overtreatment due to targeted biopsy was 2.7% (28/1020). CONCLUSIONS AND CLINICAL IMPLICATIONS: Our multicenter study revealed no strong evidence that targeted biopsy results could lead to a high risk of overtreatment. PATIENT SUMMARY: In the diagnosis pathway for prostate cancer, results for targeted biopsies guided by magnetic resonance imaging (MRI) scans lead to a negligible proportion of overtreatment.

Transperineal or Transrectal Magnetic Resonance Imaging-targeted Biopsy for Prostate Cancer Detection.

BACKGROUND AND OBJECTIVE: A notable paradigm shift has emerged in the choice of prostate biopsy approach, with a transition from transrectal biopsy (TRBx) to transperineal biopsy (TPBx) driven by the lower risk of severe urinary tract infections. The impact of this change on detection of clinically significant prostate cancer (csPCa) remains a subject of debate. Our aim was to compare the csPCa detection rate of TRBx and TPBx. METHODS: Patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies for clinically localized PCa at 15 European referral centers from 2016 to 2023 were included. A propensity score matching (PSM) analysis was performed to minimize selection biases. Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). KEY FINDINGS AND LIMITATIONS: Of 3949 patients who met the study criteria, 2187 underwent TRBx and 1762 underwent TPBx. PSM resulted in 1301 matched pairs for analysis. Patient demographics and tumor characteristics were comparable in the matched cohorts. TPBx versus TRBx was associated with greater detection of csPCa, whether defined as International Society of Urological Pathology grade group ≥2 (51% vs 45%; OR 1.37, 95% CI 1.15-1.63; p = 0.001) or grade group ≥3 (29% vs 23%; OR 1.38, 95% CI 1.13-1.67; p = 0.001). Similar results were found when considering MRI-targeted biopsy alone and after stratifying patients according to tumor location, Prostate Imaging-Reporting and Data System score, and clinical features. Limitations include the retrospective nature of the study and the absence of centralized MRI review. CONCLUSIONS: Our findings bolster existing understanding of the additional advantages offered by TPBx. Further randomized trials to fully validate these findings are awaited. PATIENT SUMMARY: We compared the rate of detection of clinically significant prostate cancer with magnetic resonance imaging (MRI)-guided biopsies in which the sample needle is passed through the perineum or the rectum. Our results suggest that the perineal approach is associated with better detection of aggressive prostate cancer.

The Added Value of Side-specific Systematic Biopsy in Patients Diagnosed by Magnetic Resonance Imaging-targeted Prostate Biopsy.

BACKGROUND: Systematic biopsy (SB) combined with magnetic resonance imaging (MRI)-targeted biopsy is still recommended considering the risk of missing clinically significant prostate cancer (csPCa). OBJECTIVE: To evaluate the added value in csPCa detection on side-specific SB relative to MRI lesion and to externally validate the Noujeim risk stratification model that predicts the risk of csPCa on distant SB cores relative to the index MRI lesion. DESIGN, SETTING, AND PARTICIPANTS: Overall, 4841 consecutive patients diagnosed by MRI-targeted biopsy and SB for Prostate Imaging Reporting and Data System score ≥3 lesions were identified from a prospectively maintained database between January 2016 and April 2023 at 15 European referral centers. A total of 2387 patients met the inclusion criteria and were included in the analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: McNemar's test was used to compare the csPCa detection rate between several biopsy strategies including MRI-targeted biopsy, side-specific SB, and a combination of both. Model performance was evaluated in terms of discrimination using area under the receiver operation characteristic curve (AUC), calibration plots, and decision curve analysis. Clinically significant prostate cancer was defined as International Society of Urological Pathology grade group ≥2. RESULTS AND LIMITATIONS: Overall, the csPCa detection rate was 49%. Considering MRI-targeted biopsy as reference, the added values in terms of csPCa detection were 5.8% (relative increase of 13%), 4.2% (relative increase of 9.8%), and 2.8% (relative increase of 6.1%) for SB, ipsilateral SB, and contralateral SB, respectively. Only 35 patients (1.5%) exclusively had csPCa on contralateral SB (p < 0.001). Considering patients with csPCa on MRI-targeted biopsy and ipsilateral SB, the upgrading rate was 2% (20/961) using contralateral SB (p < 0.001). The Noujeim model exhibited modest performance (AUC of 0.63) when tested using our validation set. CONCLUSIONS: The added value of contralateral SB was negligible in terms of cancer detection and upgrading rates. The Noujeim model could be included in the decision-making process regarding the appropriate prostate biopsy strategy. PATIENT SUMMARY: In the present study, we collected a set of patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies for the detection of prostate cancer. We found that biopsies taken at the opposite side of the MRI suspicious lesion have a negligible impact on cancer detection. We also validate a risk stratification model that predicts the risk of cancer on biopsies beyond 10 mm from the initial lesion, which could be used in daily practice to improve the personalization of the prostate biopsy.

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.

Comparing Robotic-Assisted to Open Radical Cystectomy in the Management of Non-Muscle-Invasive Bladder Cancer: A Propensity Score Matched-Pair Analysis.

BACKGROUND: For non-muscle-invasive bladder cancer (NMIBC) requiring radical surgery, limited data are available comparing robotic-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) to open radical cystectomy (ORC). The objective of this study was to compare the two surgical techniques. METHODS: A multicentric cohort of 593 patients with NMIBC undergoing iRARC or ORC between 2015 and 2020 was prospectively gathered. Perioperative and pathologic outcomes were compared. RESULTS: A total of 143 patients operated on via iRARC were matched to 143 ORC patients. Operative time was longer in the iRARC group (p = 0.034). Blood loss was higher in the ORC group (p < 0.001), with a consequent increased post-operative transfusion rate in the ORC group (p = 0.003). Length of stay was longer in the ORC group (p = 0.007). Post-operative complications did not differ significantly (all p > 0.05). DFS at 60 months was 55.9% in ORC and 75.2% in iRARC with a statistically significant difference (p = 0.033) found in the univariate analysis. CONCLUSION: We found that iRARC for patients with NMIBC is safe, associated with a lower blood loss, a lower transfusion rate and a shorter hospital stay compared to ORC. Complication rates were similar. No significant differences in survival analyses emerged across the two techniques.

PSMA PET/CT for Response Assessment and Overall Survival Prediction in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Androgen Receptor Pathway Inhibitors.

We aimed to evaluate the role of prostate-specific membrane antigen (PSMA) PET/CT for response assessment and outcome prediction in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with androgen receptor pathway inhibitors (ARPIs), including abiraterone acetate or enzalutamide. Methods: We retrospectively analyzed 30 ARPI-treated mCRPC patients who underwent 68Ga-PSMA-11 PET/CT within 8 wk before (baseline) and 12 ± 4 wk after treatment initiation. Total PSMA tumor volume was calculated using the fixed threshold method (SUV ≥ 3). Patients were categorized as PSMA responders (PSMA-Rs) or PSMA nonresponders (PSMA-NRs) on the basis of both European Association of Urology/European Association of Nuclear Medicine (EAU/EANM) criteria and Response Evaluation Criteria in PSMA PET/CT (RECIP) 1.0. PSMA-R included patients with a complete response, a partial response, or stable disease, and PSMA-NR included those with progressive disease. On the basis of prostate-specific antigen (PSA), patients were classified as biochemical responders if PSA decreased by at least 50% and as nonresponders if it did not. The Φ-coefficient was used to evaluate the correlation of PSMA- and PSA-based responses. Survival analysis was performed using the Cox regression hazard model and the Kaplan-Meier method. Predictive accuracy was tested for both response criteria. Results: On the basis of PSMA PET/CT, 13 (43%) patients were PSMA-NR according to the EAU/EANM criteria and 11 (37%) patients were PSMA-NR according to RECIP 1.0. Significant correlations were observed between PSMA- and PSA-based responses for both criteria (Φ = 0.79 and 0.66, respectively). After a median follow-up of 25 mo (interquartile range, 21-43 mo), the median overall survival was significantly longer for PSMA-R than PSMA-NR (54 vs. 22 mo) for both the EAU/EANM criteria and RECIP 1.0, with hazard ratios of 6.9 (95% CI, 1.9-26; P = 0.004) and 5.6 (95% CI, 1.69-18.26, P = 0.005), respectively. No significant difference in predictive accuracy was found between the 2 criteria (C-index, 0.79 vs. 0.76, respectively, P = 0.54). Flare phenomena at the second PSMA PET study were not observed in our cohort. Conclusion: Our results demonstrate that PSMA PET/CT is a valuable imaging biomarker for response assessment and overall survival prediction when performed at 3 mo after ARPI treatment initiation in mCRPC patients. Both proposed PSMA response criteria (EAU/EANM and RECIP 1.0) seem to perform equally well. No PSMA flare was observed. Prospective validation of these findings is strongly needed.

MRI lesion size is more important than the number of positive biopsy cores in predicting adverse features and recurrence after radical prostatectomy: implications for active surveillance criteria in intermediate-risk patients.

INTRODUCTION: To determine associations between prostate cancer (PCa) tumor burden measured on biopsy or multiparametric magnetic resonance imaging (mpMRI) and outcomes in intermediate-risk (IR) International Society of Urological Pathology (ISUP) grade 2 men managed with primary radical prostatectomy (RP). METHODS: This retrospective, multicenter study was conducted in eight referral centers. The cohort included IR PCa patients who had ISUP 2 at biopsy. We defined biopsy tumor burden as low/high based on the absence/presence of more than 25% positive cores. Tumor burden on imaging was defined as low/high based on maximum lesion diameter, <15 mm and ≥15 mm at mpMRI, respectively. The histological endpoint of the study was adverse features at RP, defined as ≥pT3a stage and/or lymph node invasion and/or ISUP ≥3 at final pathology. The clinical endpoint was biochemical recurrence (BCR) after RP. RESULTS: A total of 698 IR patients was included, of whom 335 (48%) had adverse features. In multivariate logistic regression analysis, there was no statistical association between tumor burden at biopsy and adverse features (p = 0.7). Tumor size ≥15 mm at mpMRI was significantly associated with adverse pathology (OR 1.65, 95%CI 1.14-2.39; p = 0.01). No significant association was observed between tumor burden at biopsy and BCR (p = 0.4). Tumor size ≥15 mm at mpMRI was significantly associated with BCR (HR 1.96, 95% CI 1.01-3.80; p = 0.04). CONCLUSIONS: Our data support extending the inclusion criteria to ISUP 2 men with >25% positive cores, provided they have a low tumor size at mpMRI (<15 mm). Prospective studies should be performed to validate these findings.

Peering through the PSMA PET Lens: The Role of the European Association of Urology Biochemical Recurrence Risk Groups after Radical Prostatectomy.

(1) Background: The European Association of Urology (EAU) biochemical recurrence (BCR) risk grouping relies on data from historical cohorts that used conventional imaging techniques. In the era of PSMA PET/CT, we compared the patterns of positivity in the two risk groups and provided insight into positivity predictive factors. (2) Methods: Data from 1185 patients who underwent 68Ga-PSMA-11PET/CT for BCR was analyzed, out of which 435 patients treated initially treated by radical prostatectomy were included in the final analysis. (3) Results: A significantly higher rate of positivity in the BCR high-risk group was observed (59% vs. 36%, p < 0.001). BCR low-risk group demonstrated more local (26% vs. 6%, p < 0.001) and oligometastatic (100% vs. 81%, p < 0.001) recurrences. The BCR risk group and PSA level at the time of PSMA PET/CT were independent predictive factors of positivity. (4) Conclusions: This study confirms that the EAU BCR risk groups have different rates of PSMA PET/CT positivity. Even with a lower rate in the BCR low-risk group, oligometastatic disease was 100% in those with distant metastases. Given the presence of discordant positivity and risk classification, integrating PSMA PET/CT positivity predictors into risk calculators for BCR might improve patient classification for subsequent treatment options. Future prospective studies are still needed to validate the above findings and assumptions.

Late-onset enteric fistula following radical cystectomy for bladder cancer: A case report.

Enteric fistula is a rare early onset complication following radical cystectomy with urinary diversion for bladder cancer. We present the case of a 55-year-old woman presenting with an insidious fistula between the ileum and the ileal conduit, diagnosed 20-months after the initial surgery. A single surgical intervention was sufficient for treating this rare etiology. We herein present the case and discuss the available literature on the diagnosis and treatment of such complication.

A Novel Nomogram to Identify Candidates for Focal Therapy Among Patients with Localized Prostate Cancer Diagnosed via Magnetic Resonance Imaging-Targeted and Systematic Biopsies: A European Multicenter Study.

BACKGROUND: Suitable selection criteria for focal therapy (FT) are crucial to achieve success in localized prostate cancer (PCa). OBJECTIVE: To develop a multivariable model that better delineates eligibility for FT and reduces undertreatment by predicting unfavorable disease at radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: Data were retrospectively collected from a prospective European multicenter cohort of 767 patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies followed by RP in eight referral centers between 2016 and 2021. The Imperial College of London eligibility criteria for FT were applied: (1) unifocal MRI lesion with Prostate Imaging-Reporting and Data System score of 3-5; (2) prostate-specific antigen (PSA) ≤20 ng/ml; (3) cT2-3a stage on MRI; and (4) International Society of Urological Pathology grade group (GG) 1 and ≥6 mm or GG 2-3. A total of 334 patients were included in the final analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was unfavorable disease at RP, defined as GG ≥4, and/or lymph node invasion, and/or seminal vesicle invasion, and/or contralateral clinically significant PCa. Logistic regression was used to assess predictors of unfavorable disease. The performance of the models including clinical, MRI, and biopsy information was evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis. A coefficient-based nomogram was developed and internally validated. RESULTS AND LIMITATIONS: Overall, 43 patients (13%) had unfavorable disease on RP pathology. The model including PSA, clinical stage on digital rectal examination, and maximum lesion diameter on MRI had an AUC of 73% on internal validation and formed the basis of the nomogram. Addition of other MRI or biopsy information did not significantly improve the model performance. Using a cutoff of 25%, the proportion of patients eligible for FT was 89% at the cost of missing 30 patients (10%) with unfavorable disease. External validation is required before the nomogram can be used in clinical practice. CONCLUSIONS: We report the first nomogram that improves selection criteria for FT and limits the risk of undertreatment. PATIENT SUMMARY: We conducted a study to develop a better way of selecting patients for focal therapy for localized prostate cancer. A novel predictive tool was developed using the prostate-specific antigen (PSA) level measured before biopsy, tumor stage assessed via digital rectal examination, and lesion size on magnetic resonance imaging (MRI) scans. This tool improves the prediction of unfavorable disease and may reduce the risk of undertreatment of localized prostate cancer when using focal therapy.

Development, multi-institutional external validation, and algorithmic audit of an artificial intelligence-based Side-specific Extra-Prostatic Extension Risk Assessment tool (SEPERA) for patients undergoing radical prostatectomy: a retrospective cohort study.

BACKGROUND: Accurate prediction of side-specific extraprostatic extension (ssEPE) is essential for performing nerve-sparing surgery to mitigate treatment-related side-effects such as impotence and incontinence in patients with localised prostate cancer. Artificial intelligence (AI) might provide robust and personalised ssEPE predictions to better inform nerve-sparing strategy during radical prostatectomy. We aimed to develop, externally validate, and perform an algorithmic audit of an AI-based Side-specific Extra-Prostatic Extension Risk Assessment tool (SEPERA). METHODS: Each prostatic lobe was treated as an individual case such that each patient contributed two cases to the overall cohort. SEPERA was trained on 1022 cases from a community hospital network (Trillium Health Partners; Mississauga, ON, Canada) between 2010 and 2020. Subsequently, SEPERA was externally validated on 3914 cases across three academic centres: Princess Margaret Cancer Centre (Toronto, ON, Canada) from 2008 to 2020; L'Institut Mutualiste Montsouris (Paris, France) from 2010 to 2020; and Jules Bordet Institute (Brussels, Belgium) from 2015 to 2020. Model performance was characterised by area under the receiver operating characteristic curve (AUROC), area under the precision recall curve (AUPRC), calibration, and net benefit. SEPERA was compared against contemporary nomograms (ie, Sayyid nomogram, Soeterik nomogram [non-MRI and MRI]), as well as a separate logistic regression model using the same variables included in SEPERA. An algorithmic audit was performed to assess model bias and identify common patient characteristics among predictive errors. FINDINGS: Overall, 2468 patients comprising 4936 cases (ie, prostatic lobes) were included in this study. SEPERA was well calibrated and had the best performance across all validation cohorts (pooled AUROC of 0·77 [95% CI 0·75-0·78] and pooled AUPRC of 0·61 [0·58-0·63]). In patients with pathological ssEPE despite benign ipsilateral biopsies, SEPERA correctly predicted ssEPE in 72 (68%) of 106 cases compared with the other models (47 [44%] in the logistic regression model, none in the Sayyid model, 13 [12%] in the Soeterik non-MRI model, and five [5%] in the Soeterik MRI model). SEPERA had higher net benefit than the other models to predict ssEPE, enabling more patients to safely undergo nerve-sparing. In the algorithmic audit, no evidence of model bias was observed, with no significant difference in AUROC when stratified by race, biopsy year, age, biopsy type (systematic only vs systematic and MRI-targeted biopsy), biopsy location (academic vs community), and D'Amico risk group. According to the audit, the most common errors were false positives, particularly for older patients with high-risk disease. No aggressive tumours (ie, grade >2 or high-risk disease) were found among false negatives. INTERPRETATION: We demonstrated the accuracy, safety, and generalisability of using SEPERA to personalise nerve-sparing approaches during radical prostatectomy. FUNDING: None.

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.

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.

Do perioperative blood transfusions impact oncological outcomes of robot-assisted radical cystectomy with intracorporeal urinary diversion? Results from a large multi-institutional registry.

BACKGROUND: Blood transfusions (BT) have been associated with adverse oncologic outcomes in multiple malignancies including open radical cystectomy (ORC) for urothelial carcinoma of the bladder (UCB). Robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) delivers similar oncologic outcomes compared to ORC, yet with lower blood loss and reduced transfusions. However, the impact of BT after robotic cystectomy is still unknown. METHODS: This is a multicenter study including patients treated for UCB with RARC and ICUD in 15 academic institutions, between January 2015 and January 2022. BT were administered during surgery (intraoperative blood transfusions, iBT) or during the first 30 days after surgery (post-operative blood transfusions, pBT). The association of iBT and pBT with recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) were evaluated by univariate and multivariate regression analysis. RESULTS: A total of 635 patients were included in the study. Overall, 35/635 patients (5.51%) received iBT while 70/635 (11.0%) received pBT. After a mean follow-up of 23±18 months, 116 patients (18.3%) had died, including 96 (15.1%) from bladder cancer. Recurrence occurred in 146 patients (23%). iBT were associated with decreased RFS, CSS and OS (P<0.001) on univariate Cox analysis. After adjusting for clinicopathologic covariates, iBT were associated only with the risk of recurrence (HR: 1.7; 95% CI, 1.0-2.8, P=0.04). pBT were not significantly associated to RFS, CSS or OS on univariate and multivariate Cox regression models (P>0.05). CONCLUSIONS: In the present study, patients treated by RARC with ICUD for UCB have a higher risk of recurrence after iBT, yet no significant association with CSS and OS was found. pBT are not associated with worse oncological prognosis.

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.

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.