The testosterone replacement therapy for prostate cancer patients: Time to take the leap?

The advent of new systemic therapies resulted in a significant decrease in prostate cancer (PCa) death in the past decades. It comes at the cost of an increase in the proportion of men living with long-term treatment-induced hypogonadism. In a population of men with no history of PCa, the testosterone replacement therapy (TRT) proved its ability to both improve erectile function and reduce cardiovascular morbidity, translating into an improved overall survival. Whether TRT is safe and efficient in PCa patients remains an open question. Here, we present an overview on the safety of TRT for PCa patients and discuss the optimal population eligible for TRT after the PCa treatment.

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.

Influential Factors Impacting Treatment Decision-making and Decision Regret in Patients with Localized or Locally Advanced Prostate Cancer: A Systematic Literature Review.

CONTEXT: Treatment decision-making (TDM) for patients with localized (LPC) or locally advanced (LAPC) prostate cancer is complex, and post-treatment decision regret (DR) is common. The factors driving TDM or predicting DR remain understudied. OBJECTIVE: Two systematic literature reviews were conducted to explore the factors associated with TDM and DR. EVIDENCE ACQUISITION: Three online databases, select congress proceedings, and gray literature were searched (September 2022). Publications on TDM and DR in LPC/LAPC were prioritized based on the following: 2012 onward, ≥100 patients, journal article, and quantitative data. The Preferred Reporting Items Reviews and Meta-analyses guidelines were followed. Influential factors were those with p < 0.05; for TDM, factors described as "a decision driver", "associated", "influential", or "significant" were also included. The key factors were determined by number of studies, consistency of evidence, and study quality. EVIDENCE SYNTHESIS: Seventy-five publications (68 studies) reported TDM. Patient participation in TDM was reported in 34 publications; overall, patients preferred an active/shared role. Of 39 influential TDM factors, age, ethnicity, external factors (physician recommendation most common), and treatment characteristics/toxicity were key. Forty-nine publications reported DR. The proportion of patients experiencing DR varied by treatment type: 7-43% (active surveillance), 12-57% (radical prostatectomy), 1-49% (radiotherapy), 28-49% (androgen-deprivation therapy), and 21-47% (combination therapy). Of 42 significant DR factors, treatment toxicity (sexual/urinary/bowel dysfunction), patient role in TDM, and treatment type were key. CONCLUSIONS: The key factors impacting TDM were physician recommendation, age, ethnicity, and treatment characteristics. Treatment toxicity and TDM approach were the key factors influencing DR. To help patients navigate factors influencing TDM and to limit DR, a shared, consensual TDM approach between patients, caregivers, and physicians is needed. PATIENT SUMMARY: We looked at factors influencing treatment decision-making (TDM) and decision regret (DR) in patients with localized or locally advanced prostate cancer. The key factors influencing TDM were doctor's recommendation, patient age/ethnicity, and treatment side effects. A shared, consensual TDM approach between patients and doctors was found to limit DR.

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.

EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer-2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent.

BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines provide recommendations for the management of clinically localised prostate cancer (PCa). This paper aims to present a summary of the 2024 version of the EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on the screening, diagnosis, and treatment of clinically localised PCa. METHODS: The panel performed a literature review of all new data published in English, covering the time frame between May 2020 and 2023. The guidelines were updated, and a strength rating for each recommendation was added based on a systematic review of the evidence. KEY FINDINGS AND LIMITATIONS: A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is considered, a combination of targeted and regional biopsies should be performed. Prostate-specific membrane antigen positron emission tomography imaging is the most sensitive technique for identifying metastatic spread. Active surveillance is the appropriate management for men with low-risk PCa, as well as for selected favourable intermediate-risk patients with International Society of Urological Pathology grade group 2 lesions. Local therapies are addressed, as well as the management of persistent prostate-specific antigen after surgery. A recommendation to consider hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term intensified hormonal treatment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. These PCa guidelines reflect the multidisciplinary nature of PCa management. PATIENT SUMMARY: This article is the summary of the guidelines for "curable" prostate cancer. Prostate cancer is "found" through a multistep risk-based screening process. The objective is to find as many men as possible with a curable cancer. Prostate cancer is curable if it resides in the prostate; it is then classified into low-, intermediary-, and high-risk localised and locally advanced prostate cancer. These risk classes are the basis of the treatments. Low-risk prostate cancer is treated with "active surveillance", a treatment with excellent prognosis. For low-intermediary-risk active surveillance should also be discussed as an option. In other cases, active treatments, surgery, or radiation treatment should be discussed along with the potential side effects to allow shared decision-making.

Magnetic Resonance Imaging in Prostate Cancer Screening: A Systematic Review and Meta-Analysis.

Importance: Prostate magnetic resonance imaging (MRI) is increasingly integrated within the prostate cancer (PCa) early detection pathway. Objective: To systematically evaluate the existing evidence regarding screening pathways incorporating MRI with targeted biopsy and assess their diagnostic value compared with prostate-specific antigen (PSA)-based screening with systematic biopsy strategies. Data Sources: PubMed/MEDLINE, Embase, Cochrane/Central, Scopus, and Web of Science (through May 2023). Study Selection: Randomized clinical trials and prospective cohort studies were eligible if they reported data on the diagnostic utility of prostate MRI in the setting of PCa screening. Data Extraction: Number of screened individuals, biopsy indications, biopsies performed, clinically significant PCa (csPCa) defined as International Society of Urological Pathology (ISUP) grade 2 or higher, and insignificant (ISUP1) PCas detected were extracted. Main Outcomes and Measures: The primary outcome was csPCa detection rate. Secondary outcomes included clinical insignificant PCa detection rate, biopsy indication rates, and the positive predictive value for the detection of csPCa. Data Synthesis: The generalized mixed-effect approach with pooled odds ratios (ORs) and random-effect models was used to compare the MRI-based and PSA-only screening strategies. Separate analyses were performed based on the timing of MRI (primary/sequential after a PSA test) and cutoff (Prostate Imaging Reporting and Data System [PI-RADS] score ≥3 or ≥4) for biopsy indication. Results: Data were synthesized from 80 114 men from 12 studies. Compared with standard PSA-based screening, the MRI pathway (sequential screening, PI-RADS score ≥3 cutoff for biopsy) was associated with higher odds of csPCa when tests results were positive (OR, 4.15; 95% CI, 2.93-5.88; P ≤ .001), decreased odds of biopsies (OR, 0.28; 95% CI, 0.22-0.36; P ≤ .001), and insignificant cancers detected (OR, 0.34; 95% CI, 0.23-0.49; P = .002) without significant differences in the detection of csPCa (OR, 1.02; 95% CI, 0.75-1.37; P = .86). Implementing a PI-RADS score of 4 or greater threshold for biopsy selection was associated with a further reduction in the odds of detecting insignificant PCa (OR, 0.23; 95% CI, 0.05-0.97; P = .048) and biopsies performed (OR, 0.19; 95% CI, 0.09-0.38; P = .01) without differences in csPCa detection (OR, 0.85; 95% CI, 0.49-1.45; P = .22). Conclusion and relevance: The results of this systematic review and meta-analysis suggest that integrating MRI in PCa screening pathways is associated with a reduced number of unnecessary biopsies and overdiagnosis of insignificant PCa while maintaining csPCa detection as compared with PSA-only screening.

EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer. Part II-2024 Update: Treatment of Relapsing and Metastatic Prostate Cancer.

BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (PCa) have been updated. Here we provide a summary of the 2024 guidelines. METHODS: The panel performed a literature review of new data, covering the time frame between 2020 and 2023. The guidelines were updated and a strength rating for each recommendation was added on the basis of a systematic review of the evidence. KEY FINDINGS AND LIMITATIONS: Risk stratification for relapsing PCa after primary therapy may guide salvage therapy decisions. New treatment options, such as androgen receptor-targeted agents (ARTAs), ARTA + chemotherapy combinations, PARP inhibitors and their combinations, and prostate-specific membrane antigen-based therapy have become available for men with metastatic PCa. CONCLUSIONS AND CLINICAL IMPLICATIONS: Evidence for relapsing, metastatic, and castration-resistant PCa is evolving rapidly. These guidelines reflect the multidisciplinary nature of PCa management. The full version is available online (http://uroweb.org/guideline/ prostate-cancer/). PATIENT SUMMARY: This article summarises the 2024 guidelines for the treatment of relapsing, metastatic, and castration-resistant prostate cancer. These guidelines are based on evidence and guide doctors in discussing treatment decisions with their patients. The guidelines are updated every year.

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.

PRECISE Version 2: Updated Recommendations for Reporting Prostate Magnetic Resonance Imaging in Patients on Active Surveillance for Prostate Cancer.

BACKGROUND AND OBJECTIVE: The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) recommendations standardise the reporting of prostate magnetic resonance imaging (MRI) in patients on active surveillance (AS) for prostate cancer. An international consensus group recently updated these recommendations and identified the areas of uncertainty. METHODS: A panel of 38 experts used the formal RAND/UCLA Appropriateness Method consensus methodology. Panellists scored 193 statements using a 1-9 agreement scale, where 9 means full agreement. A summary of agreement, uncertainty, or disagreement (derived from the group median score) and consensus (determined using the Interpercentile Range Adjusted for Symmetry method) was calculated for each statement and presented for discussion before individual rescoring. KEY FINDINGS AND LIMITATIONS: Participants agreed that MRI scans must meet a minimum image quality standard (median 9) or be given a score of 'X' for insufficient quality. The current scan should be compared with both baseline and previous scans (median 9), with the PRECISE score being the maximum from any lesion (median 8). PRECISE 3 (stable MRI) was subdivided into 3-V (visible) and 3-NonV (nonvisible) disease (median 9). Prostate Imaging Reporting and Data System/Likert ≥3 lesions should be measured on T2-weighted imaging, using other sequences to aid in the identification (median 8), and whenever possible, reported pictorially (diagrams, screenshots, or contours; median 9). There was no consensus on how to measure tumour size. More research is needed to determine a significant size increase (median 9). PRECISE 5 was clarified as progression to stage ≥T3a (median 9). CONCLUSIONS AND CLINICAL IMPLICATIONS: The updated PRECISE recommendations reflect expert consensus opinion on minimal standards and reporting criteria for prostate MRI in AS. PATIENT SUMMARY: The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) recommendations are used in clinical practice and research to guide the interpretation and reporting of magnetic resonance imaging for patients on active surveillance for prostate cancer. An international panel has updated these recommendations, clarified the areas of uncertainty, and highlighted the areas for further research.

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.

Definitions, outcomes and perspectives for oligometastatic bladder cancer: towards a standardized terminology.

PURPOSE OF REVIEW: Oligometastatic (om) cancer is considered as a transitional state in between locally confined disease and widespread metastases, accessible to a multimodal treatment, combining systemic and local therapy. In urothelial bladder cancer (BCa), the definitions and the approaches to this condition are poorly standardised and mainly based on retrospective data. We aim to portray the framework for uro-oncologic terminology in omBCa and go through the latest evidence and the future perspectives. RECENT FINDINGS: Retrospective and registry data support the potential benefits of multimodality treatment for carefully selected omBCa patients, especially following a good response to systemic treatment. In 2023, a Delphi consensus has defined omBCa, allowing maximum three metastatic lesions, theoretically amenable to radical local treatment. In de-novo omBCa, surgical treatment of primary tumour might improve overall survival (OS), according to a matched registry analysis; also, consolidative radiotherapy was associated with better OS in two recent cohorts. Furthermore, metastasis-directed therapy (MDT) has shown high local control rates and promising OS (14.9-51 months) in a meta-analysis; benefits might be more pronounced for single-site omBCa and nodal or lung lesions. SUMMARY: From a clinical perspective, in de-novo omBCa, the local treatment of primary and metastatic sites might improve disease control and survival, in selected patients; in the oligorecurrent setting, MDT achieves good local symptom control with limited side effects; in selected cases, it could convey a survival benefit, too. From a research perspective, well designed prospective evidence is eagerly awaited, based on recently adopted shared definitions for omBCa.

A Comprehensive National Survey of Prostate-specific Antigen Testing and Prostate Cancer Management in France: Uncovering Regional and Temporal Disparities.

We report nationwide real-life practice in the management of prostate cancer (PC) in France in a population of 4936750 men. All prostate-specific antigen (PSA) blood tests performed between 2006 and 2018 were recorded in a National Health registry, which allowed to identify 692516 men diagnosed with PC and a control population consisting of 3899509 men without PC. PSA tests, age at diagnosis, treatments, and survival were analysed. Their management was analysed by age range and compared in the different French regions. Disparities were found in age at PSA testing and management approaches (surveillance, and local and systemic therapies). We found that 50% of men had received five PSA blood tests, but the first PSA test was taken late in life, with a peak in the decade between 65 and 75 yr of age. Adoption of monitoring was low (12%). Older men appeared to receive a late diagnosis with reduced chances of curative therapy and a subsequent increase in mortality, but cautious interpretation of our data is warranted in view of competing morbidities and other causes of death. The incidence of metastases at diagnosis, indicated by the use of systemic therapies, increased progressively from 2011 onwards. PATIENT SUMMARY: In this study, we report nationwide real-life practice in the management of prostate cancer (PC) in France in a population of 4936750 men, including 692516 patients with PC. We found that the first prostate-specific antigen test is taken too late in life, leading to a late diagnosis with reduced chances of curative therapy and a subsequent increase in mortality.

Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted Biopsies for Prostate Cancer Diagnosis: Final Results of the Randomized PERFECT trial (CCAFU-PR1).

BACKGROUND: Recent guidelines favor transperineal (TP) prostate biopsies over the transrectal (TR) approach due to a reduced sepsis risk. Yet, evidence from controlled trial comparing both approaches within the MRI-targeted pathway for significant prostate cancer (PCa) detection is lacking. OBJECTIVE: To compare the significant PCa detection rate between magnetic resonance imaging (MRI)-targeted TR and TP approaches in biopsy-naïve patients. DESIGN, SETTING, AND PARTICIPANTS: In this noninferiority controlled trial, we randomized (ratio 1:1) 270 MRI-positive biopsy-naïve patients. INTERVENTION: MRI-targeted TP versus TR biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: The primary outcome was the detection rate of significant PCa (International Society of Urological Pathology [ISUP] ≥2) in MRI-targeted biopsies. Secondary outcomes were any-grade PCa detection, detection on concomitant systematic biopsy, complications, and functional outcomes. RESULTS AND LIMITATIONS: Targeted biopsies identified significant PCa in 47.2% of TP and 54.2% of TR participants (-7%, p = 0.6235). On a per-lesion analysis, posterior lesions yielded higher detection rates via TR (59.0% vs 44.3%, p = 0.0443), while anterior lesions were more frequently detected via TP (40.6% vs 26.5%, p = 0.2228). The overall (any grade) cancer detection rate in targeted biopsies was comparable between groups: 71.3% (TP) versus 64.1% (TR; p = 0.2209) with significantly more ISUP 1 cases detected in the TP arm. Adverse events of grade ≥2 were not different between TP (35.7%) and TR (40.5%, p = 0.4256). One TR patient (0.8%) experienced grade 3 sepsis. Quality of life, and urinary and sexual function, as well as pain scores, were comparable between groups. CONCLUSIONS: Despite a comparable overall detection rate for any-grade PCa, noninferiority of TP over TR for MRI-targeted biopsies for significant PCa detection was not demonstrated. However, MRI lesion location influenced biopsy route performance, suggesting that a pragmatic approach based on lesion location might enhance significant PCa assessment. PATIENT SUMMARY: This trial compared the efficacy and safety of two biopsy approaches for prostate cancer diagnosis. Both approaches seem complementary according to the lesion location.

Unlocking the Potential of Adequate Bacillus Calmette-Guérin Immunotherapy in Very-high-risk Non-muscle-invasive Bladder Carcinoma: A Multicenter Analysis of Oncological Outcomes and Risk Dynamics.

BACKGROUND: The European Association of Urology (EAU) recommends discussing upfront radical cystectomy for all patients with very high risk (VHR) non-muscle-invasive bladder carcinoma (NMIBC), but the role of bacillus Calmette-Guérin (BCG) treatment remains controversial. OBJECTIVE: To analyze oncological outcomes in VHR NMIBC patients (EAU risk groups) treated with adequate BCG. DESIGN, SETTING, AND PARTICIPANTS: A multi-institutional retrospective study involving patients with VHR NMIBC who received adequate BCG therapy from 2007 to 2020 was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A survival analysis estimated recurrence-free survival (RFS), progression-free survival (PFS), and the cumulative incidence of cancer-specific mortality (CSM) after accounting for other causes of mortality as competing risk events and of the overall mortality (OM). Conditional survival probabilities for 0-4 yr without events were computed. Cox regression assessed the predictors of oncological outcomes. RESULTS AND LIMITATION: A total of 640 patients, with a median 47 (32-67) mo follow-up for event-free individuals, were analyzed. High-grade RFS and PFS at 5 yr were 53% (49-57%) and 78% (74-82%), respectively. The cumulative incidence of CSM and OM at 5 yr was 13% (10-16%) and 16% (13-19%), respectively. Conditional RFS, PFS, overall survival, and cancer-specific survival at 4 yr were 91%, 96%, 87%, and 94%, respectively. Cox regression identified tumor grade (hazard ratio [HR]: 1.54; 1.1-2) and size (HR: 1.3; 1.1-1.7) as RFS predictors. Tumor multiplicity predicted RFS (HR: 1.6; 1.3-2), PFS (HR: 2; 1.2-3.3), and CSM (HR: 2; 1.2-3.2), while age predicted OM (HR: 1.48; 1.1-2). CONCLUSIONS: Patients with VHR NMIBC who receive adequate BCG therapy have a more favorable prognosis than predicted by EAU risk groups, especially among those with a sustained response, in whom continuing maintenance therapy emerges as a viable alternative to radical cystectomy. PATIENT SUMMARY: Our research shows that a sustained response to bacillus Calmette-Guérin in patients can lead to favorable outcomes, serving as a viable alternative to cystectomy for select cases.

An updated model for predicting side-specific extraprostatic extension in the era of MRI-targeted biopsy.

PURPOSE: Accurate prediction of extraprostatic extension (EPE) is pivotal for surgical planning. Herein, we aimed to provide an updated model for predicting EPE among patients diagnosed with MRI-targeted biopsy. MATERIALS AND METHODS: We analyzed a multi-institutional dataset of men with clinically localized prostate cancer diagnosed by MRI-targeted biopsy and subsequently underwent prostatectomy. To develop a side-specific predictive model, we considered the prostatic lobes separately. A multivariable logistic regression analysis was fitted to predict side-specific EPE. The decision curve analysis was used to evaluate the net clinical benefit. Finally, a regression tree was employed to identify three risk categories to assist urologists in selecting candidates for nerve-sparing, incremental nerve sparing and non-nerve-sparing surgery. RESULTS: Overall, data from 3169 hemi-prostates were considered, after the exclusion of prostatic lobes with no biopsy-documented tumor. EPE was present on final pathology in 1,094 (34%) cases. Among these, MRI was able to predict EPE correctly in 568 (52%) cases. A model including PSA, maximum diameter of the index lesion, presence of EPE on MRI, highest ISUP grade in the ipsilateral hemi-prostate, and percentage of positive cores in the ipsilateral hemi-prostate achieved an AUC of 81% after internal validation. Overall, 566, 577, and 2,026 observations fell in the low-, intermediate- and high-risk groups for EPE, as identified by the regression tree. The EPE rate across the groups was: 5.1%, 14.9%, and 48% for the low-, intermediate- and high-risk group, respectively. CONCLUSION: In this study we present an update of the first side-specific MRI-based nomogram for the prediction of extraprostatic extension together with updated risk categories to help clinicians in deciding on the best approach to nerve-preservation.

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.

Oncologic Outcomes in Patients with Residual Upper Tract Urothelial Carcinoma Following Neoadjuvant Chemotherapy.

BACKGROUND AND OBJECTIVE: Growing evidence supports the use of neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC). However, the implications of residual UTUC at radical nephroureterectomy (RNU) after NAC are not well characterized. Our objective was to compare oncologic outcomes for pathologic risk-matched patients who underwent RNU for UTUC who either received NAC or were chemotherapy-naïve. METHODS: We retrospectively identified 1993 patients (including 112 NAC recipients) who underwent RNU for nonmetastatic, high-grade UTUC between 1985 and 2022 in a large, international, multicenter cohort. We divided the cohort into low-risk and high-risk groups defined according to pathologic findings of muscle invasion and lymph node involvement at RNU. Recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) estimates were calculated using the Kaplan-Meier method. Multivariable analyses were performed to determine clinical and demographic factors associated with these outcomes. KEY FINDINGS AND LIMITATIONS: Among patients with low-risk pathology at RNU, RFS, OS, and CSS were similar between the NAC and chemotherapy-naïve groups. Among patients with high-risk pathology at RNU, the NAC group had poorer RFS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 2.10-4.48), OS (HR 2.06, 95% CI 1.33-3.20), and CSS (subdistribution HR 2.54, 95% CI 1.37-4.69) in comparison to the pathologic risk-matched, chemotherapy-naïve group. Limitations include the lack of centralized pathologic review. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients with residual invasive disease at RNU after NAC represent a uniquely high-risk population with respect to oncologic outcomes. There is a critical need to determine an optimal adjuvant approach for these patients. PATIENT SUMMARY: We studied a large, international group of patients with cancer of the upper urinary tract who underwent surgery either with or without receiving chemotherapy beforehand. We identified a high-risk subgroup of patients with residual aggressive cancer after chemotherapy and surgery who should be prioritized for clinical trials and drug development.