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Background and Objective: Intravesical instillation of chemotherapy (IIC) after radical surgery for upper urinary tract urothelial carcinoma (UTUC) reduces the risk of intravesical recurrence (IVR). However, compliance is low because of possible extravesical leakage after bladder cuff excision. The aim of this study was to evaluate the efficacy of preoperative IIC in reducing the risk of IVR., Methods: In this prospective, single-arm, multi-institutional, phase 2 clinical trial, 190 chemonaïve patients with primary UTUC without prior or concurrent bladder cancer received a single intravesical instillation of mitomycin C for 1-2 hr within 3 h before surgery. The primary endpoint was the 2-yr histologically confirmed IVR rate, with a target reduction of >40% (from 33.2% according to literature data to <20%). A historical cohort of 247 patients with UTUC who did not receive perioperative IIC served as the reference. Secondary endpoints included compliance, toxicity, and IVR-free survival, which was analyzed via multivariable Cox regression and stratified by previous diagnostic ureteroscopy (d-URS)., Key Findings and Limitations: The 2-yr IVR rate was 24% (95% confidence interval [CI] 18-31%) on intention-to-treat analysis and 23% (95% CI 13-32%) on per-protocol analysis. Multivariable analysis revealed that d-URS was associated with higher IVR risk. In the REBACARE cohort, patients without d-URS had threefold lower IVR risk (hazard ratio 0.33, 95% CI 0.12-0.87) in comparison to the reference cohort. Compliance with preoperative instillation was 96% and no grade >2 toxicity occurred., Conclusions and Clinical Implications: Preoperative IIC with mitomycin C was feasible and well tolerated and significantly reduced IVR risk for patients without d-URS. These findings suggest that preoperative IIC is a viable strategy for this subset of UTUC patients and that d-URS should be performed judiciously., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objective: Patient-reported outcome measures (PROMs) are increasingly being used to capture the patients' perspective of their functional status and quality of life (QoL). Big data can help us better understand patient-reported outcomes (PROs). Using prospectively collected data from the Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) consortium, we aimed to describe the functional status and QoL in men with prostate cancer (PCa) treated with active surveillance (AS), radical prostatectomy (RP), and radiotherapy (RT), and to demonstrate the applicability of PROM data on a large scale and at a European level., Methods: We identified data sources that collected QoL data using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-PR25, or Expanded Prostate Cancer Index Composite (EPIC)-26/50 questionnaires. Aggregated summary scores for urinary, bowel, and sexual dysfunction, global health status, and QoL were shared for each data source., Key Findings and Limitations: We identified eight data sources originating from various settings: routine hospital data, embedded research PRO collection, survey data collected by a patient organization, multi-institutional prospective cohort study, and registry data. PRO data were available for 709 men on AS, 20 508 on RP, and 3417 on RT, with a median time between diagnosis and PROM assessment ranging from 1 to 8.7 yr. Most men were diagnosed with Gleason ≤7 disease, and T1 or T2 PCa. We observed that sexual dysfunction was the most affected PRO and found large differences between data sources., Conclusions and Clinical Implications: Our results support the feasibility of PRO assessment using big data in Europe. Implementation of PROMs in clinical practice and the use of standardized methods could improve value-based health care provision., Patient Summary: In this study, we combined several data sources that reported urinary, bowel, and sexual dysfunction, global health status, and quality of life. We identified eight data sources and show that sexual function is the most affected domain after treatment., (© 2024 The Author(s).)

Background and Objective: In 2019 and 2021, Europa Uomo initiated the Europa Uomo Patient Reported Outcome Study (EUPROMS) and the EUPROMS 2.0 survey, with the goal of collecting data on patients' self-reported perspective on physical and mental well-being outside of a clinical trial setting, to be able to investigate the burden of prostate cancer (PCa) treatment from a patient-to-patient perspective. Acknowledging the importance of collecting quality of life (QoL) follow-up data, a 1-yr follow-up (1yrFU) study was conducted to assess the effect of additional PCa treatment on QoL., Methods: Men with PCa who participated in the EUPROMS 2.0 survey and indicated that they were open to collection of a follow-up measurement were reinvited to complete the 1yrFU survey. The EUPROMS 2.0 1yrFU survey included the validated European Quality of Life 5 Dimension 5 Level (EQ-5D-5L), European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30), Expanded Prostate Cancer Index Composite Short Form (EPIC-26), and International Index of Erectile Function (IIEF)-15 overall satisfaction domains. Descriptive statistics were used to assess demographic characteristics and to analyze the patient-reported outcome data., Key Findings and Limitations: A total of 1006 (54%) men completed the survey. The median age at the time of questionnaire completion was 72 yr (interquartile range 66-76 yr). Of them, 641 men (64%) underwent no new treatment, while 365 men (36%) underwent new treatment, including 247 (247/365, 68%) for PCa. In total, 114 patients (46%) underwent new androgen deprivation therapy (ADT) and 81 (33%) new external beam radiotherapy (EBRT). It is indicated that the impact of new ADT and EBRT on sexual function is immediate and detrimental, and continues to last over time. However, for men who underwent EBRT or radical prostatectomy earlier and did not undergo new treatment, slight improvements on various domains are reported., Conclusions and Clinical Implications: The EUPROMS 2.0 1yrFU study provides additional information on treatments that are already in common use and will help future PCa patients to make informed and shared decisions on PCa treatment., Patient Summary: The follow-up data on quality of life collected by Europa Uomo can be used to inform future prostate cancer (PCa) patients about the impact of undergoing (multiple) PCa treatment(s)., (© 2024 The Author(s).)

Background and Objective: Tailored treatment for prostate cancer (PCa) requires accurate risk stratification. This study examines the effectiveness of the European Association of Urology (EAU) classification in predicting long-term PCa-specific mortality (PCSM) and assesses whether an alternative system can improve the identification of patients with low-risk disease., Methods: This study included two cohorts of patients with localized PCa: one with screen-detected PCa (n = 1563; S-cohort) and the other with clinically detected PCa (n = 755; C-cohort), all from a population-based, randomized screening study, who underwent primary radical prostatectomy or radiation monotherapy. Patients were stratified according to the traditional EAU risk classification and an alternative risk classification where low-risk disease is adjusted according to contemporary active surveillance (AS) eligibility criteria. The 15-yr time-dependent area under the curve (AUC) and the cumulative incidence of PCSM at 15 yr after diagnosis were assessed for each risk classification and cohort., Key Findings and Limitations: With a median follow-up of 20 yr in the S-cohort and 12 yr in the C-cohort, the EAU classification demonstrated 15-yr AUCs of 0.76 (95% confidence interval [CI]: 0.71-0.80) and 0.72 (95% CI: 0.65-0.79), respectively, for predicting PCSM. The alternative classification showed a 15-yr AUC of 0.74 (95% CI: 0.69-0.79) in the S-cohort and 0.75 (95% CI: 0.68-0.81) in the C-cohort. The alternative classification identified 45% more men having a low risk in the S-cohort and 83% more in the C-cohort than the EAU classification, with no statistically significant increase in the 15-yr PCSM incidence (S-cohort subhazard ratio: 1.33 [95% CI: 0.66-2.68]; C-cohort subhazard ratio: 0.99 [95% CI: 0.29-3.38])., Conclusions and Clinical Implications: The EAU classification predicts PCSM accurately, but an alternative classification, adjusted for AS eligibility, identifies substantially more men as having a low risk. This could enhance AS acceptance and utilization in clinical practice, reducing overtreatment., Patient Summary: This study shows that while a commonly used pretreatment risk classification for prostate cancer predict disease prognosis accurately, an alternative system based on active surveillance eligibility criteria identifies many more men as having a low risk. Adopting this classification could enhance the acceptance and use of active surveillance, reducing unnecessary treatments., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

For men with prostate cancer (PCa) within the European Randomized Study of Screening for Prostate Cancer (ERSPC), the cause of death is determined by a Cause of Death Committee (CODC) that evaluates all medical records using a fixed algorithm. The aim of this study was to compare the classification of PCa-specific mortality (PCSM) between the CODC and Statistics Netherlands. We calculated the sensitivity (PCSM agreement divided by total PCSM deaths according to the CODC) and specificity (agreement for other-cause mortality [OCM] divided by total OCM deaths according to the CODC) using the last 21-yr follow-up data from ERSPC Rotterdam. For the core age group (age 55-69 yr at randomization; n  = 1732), the sensitivity was 86% (95% CI 83-89) and specificity was 93% (95% CI 91-94), with no statistical difference between the youngest ages and the oldest ages. Extrapolation of our findings to 30 yr of follow-up would result in an expected risk reduction of PCSM of 30% using data from the CODC and 33% using official statistics in favor of screening. In conclusion, our results support the use of official statistics in determining the cause of death, without compromising the main outcome of ERSPC Rotterdam., Patient Summary: We compared the classification of prostate cancer death between a dedicated trial committee and official statistics in the Netherlands. We found that official statistics are an accurate representation in determining the cause of death., (© 2024 The Author(s).)

Purpose: To investigate the detection and predictors of prostate cancer (PCA) and clinically significant prostate cancer (csPCA) in patients with positive multiparametric MRI (mpMRI) followed by a negative MRI - guided target biopsy (TB) and systematic biopsy (SB)., Materials and Methods: This retrospective multicenter study included 694 patients from 10 tertiary referral centers with an initial positive mpMRI (PI-RADS ≥ 3) and negative results on both MRI-TB and SB. Patients were classified into three groups based on follow-up: Group 1 (prostate re-biopsy without new mpMRI), Group 2 (standardized second prostate mpMRI and subsequent re-biopsy), and Group 3 (follow-up with mpMRIs and biopsy based on clinical and radiological triggers). The primary outcomes were the detection of any PCA and csPCA during follow up. Study groups were compared according to their probability of PCA and csPCA assessed with the ERSPC-MRI risk calculator. Statistical analysis included Kaplan - Meier analysis, Cox regression, and multivariable analysis for the detection of (cs)PCa., Results: The overall detection of PCA and csPCA was 26.8% and 19.3%, respectively, with varying rates in different PI-RADS groups. Group 3 had the highest 2-year and 5-year PCA-free survival (94 and 84%) and csPCA - free survival (96 and 86%). Multivariable analysis revealed a significantly higher risk of PCA and csPCA in Group 1 and 2 compared to Group 3 (p < 0.01). Clinical and radiological predictors for PCA and csPCA included higher age, prostate volume, PI-RADS score, the presence of atypical small acinar proliferation (ASAP), and a smaller number of TB and SB performed during the initial biopsy. Study limitations, include the retrospective design and reliance on clinical and radiological triggers for follow-up decisions., Conclusions: Patients with positive mpMRI but negative TB and SB results exhibit varying rates of PCA and csPCA depending on the follow up scheme. Tailored follow-up strategies are essential for optimal management in this clinical scenario., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Aims: To investigate the surgical margin status in patients with prostate cancer who underwent robot-assisted radical prostatectomy (RARP) with intraoperative neurovascular structure-adjacent frozen-section analysis (NeuroSAFE) and evaluate differences compared to patients who underwent radical prostatectomy without NeuroSAFE., Patients and Methods: Between September 2018 and January 2021, 962 patients underwent centralized RARP with NeuroSAFE. A secondary resection was performed in case of a positive surgical margin (PSM) on intraoperative frozen section (IFS) analysis to convert a PSM into a negative surgical margin (NSM). A retrospective cohort consisted of 835 patients who had undergone radical prostatectomy in a tertiary centre without NeuroSAFE between January 2000 and December 2017. We performed multivariable logistic regression to evaluate differences in risk of PSM between cohorts after controlling for clinicopathological variables., Results: Patients operated with NeuroSAFE in the centralized clinic had 29% PSM at a definitive pathological RP examination. The median cumulative length of definitive PSM was 1.1 mm (interquartile range: 0.4-3.8). Among 275 men with PSM, 136 (49%) had a cumulative length ≤1 mm and 198 (72%) ≤3 mm. After controlling for PSA, Grade group, cribriform pattern, pT-stage, and pN-stage, patients treated in the centralized clinic with NeuroSAFE had significantly lower odds on PSM (odds ratio [OR]: 0.70, 95% confidence interval [CI]: 0.56-0.88; P = 0.002), PSM length >1 mm (OR: 0.14, 95% CI: 0.09-0.22; P < 0.001), and >3 mm (OR: 0.21, 95% CI: 0.14-0.30; P < 0.001)., Conclusion: This study provides a detailed overview of surgical margin status in a centralized RP NeuroSAFE cohort. Centralization with NeuroSAFE was associated with lower PSM rates and significantly shorter PSM cumulative lengths, indicating improved control of surgical margin status., (© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.)

Patients with high-risk non-muscle-invasive bladder cancer (NMIBC) receive bacillus Calmette-Guérin (BCG) instillations to reduce the risk of progression. For patients with very high-risk NMIBC, immediate radical cystectomy may be considered, as patients who experience disease progression despite BCG treatment have a worse prognosis. However, guideline-recommended stratification for the risk of progression is based on data from patients who were not exposed to BCG. We evaluated the risk of progression in a contemporary cohort of patients with primary high-grade/grade 3 (HG/G3) T1 NMIBC (n = 1268) who received at least one BCG instillation and underwent at least one cystoscopic evaluation. The primary endpoint was the 1-yr risk of progression for all patients and for the subgroup that received adequate BCG, defined as at least five induction instillations and at least two instillations provided as a second BCG course within 6 mo. Progression was defined as detrusor muscle invasion or lymph node or distant metastasis. The 1-yr risk of progression was 6.5% (95% confidence interval [CI] 5.2-8.0) for patients with primary HG/G3 T1 NMIBC who started BCG treatment, and 4.6% (95% CI 3.3-6.4) 1 yr after the first instillation of the second BCG course for patients who received adequate BCG (n = 746). In conclusion, the contemporary risk of progression for patients with HG/G3 T1 NMIBC who receive BCG appears to be low, especially for patients who receive adequate BCG treatment. PATIENT SUMMARY: Our study shows that for patients with a high-grade bladder tumor who received in-bladder BCG (bacillus Calmette-Guérin), the risk of disease progression was 6.5% at 1 yr after their first BCG instillation. For patients who continued with BCG maintenance treatments, the risk of progression was 4.6% after the first BCG maintenance instillation., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Prostate cancer (PCa) (early) detection poses significant challenges, including unnecessary testing and the risk of potential overdiagnosis. The European Association of Urology therefore suggests an individual risk-adapted approach, incorporating risk calculators (RCs) into the PCa detection pathway. In the context of 'The PRostate Cancer Awareness and Initiative for Screening in the European Union' (PRAISE-U) project ( https://uroweb.org/praise-u ), we aim to provide an overview of the currently available clinical RCs applicable in an early PCa detection algorithm., Methods: We performed a systematic review to identify RCs predicting detection of clinically significant PCa at biopsy. A search was performed in the databases Medline ALL, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and Google Scholar for publications between January 2010 and July 2023. We retrieved relevant literature by using the terms "prostate cancer", "screening/diagnosis" and "predictive model". Inclusion criteria included systematic reviews, meta-analyses, and clinical trials. Exclusion criteria applied to studies involving pre-targeted high-risk populations, diagnosed PCa patients, or a sample sizes under 50 men., Results: We identified 6474 articles, of which 140 were included after screening abstracts and full texts. In total, we identified 96 unique RCs. Among these, 45 underwent external validation, with 28 validated in multiple cohorts. Of the externally validated RCs, 17 are based on clinical factors, 19 incorporate clinical factors along with MRI details, 4 were based on blood biomarkers alone or in combination with clinical factors, and 5 included urinary biomarkers. The median AUC of externally validated RCs ranged from 0.63 to 0.93., Conclusions: This systematic review offers an extensive analysis of currently available RCs, their variable utilization, and performance within validation cohorts. RCs have consistently demonstrated their capacity to mitigate the limitations associated with early detection and have been integrated into modern practice and screening trials. Nevertheless, the lack of external validation data raises concerns about numerous RCs, and it is crucial to factor in this omission when evaluating whether a specific RC is applicable to one's target population., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objective: While prostate cancer (PCa) incidence and mortality rates continue to rise, early detection of PCa remains highly controversial, and the research landscape is rapidly evolving. Existing systematic reviews (SRs) and meta-analyses (MAs) provide valuable insights, but often focus on single aspects of early detection, hindering a comprehensive understanding of the topic. We aim to fill this gap by providing a comprehensive SR of contemporary SRs covering different aspects of early detection of PCa in the European Union (EU) and the UK., Methods: On June 1, 2023, we searched four databases (Medline ALL via Ovid, Embase, Web of Science, and Cochrane Central Register of Controlled Trials) and Google Scholar. To avoid repetition of previous studies, only SRs (qualitative, quantitative, and/or MAs) were considered eligible. In the data, common themes were identified to present the evidence systematically., Key Findings and Limitations: We identified 1358 citations, resulting in 26 SRs eligible for inclusion. Six themes were identified: (1) invitation: men at general risk should be invited at >50 yr of age, and testing should be discontinued at >70 yr or with <10 yr of life expectancy; (2) decision-making: most health authorities discourage population-based screening and instead recommend a shared decision-making (SDM) approach, but implementation of SDM in clinical practice varies widely; decision aids help men make more informed and value-consistent screening decisions and decrease men's intention to attempt screening, but these do not affect screening uptake; (3) acceptance: facilitators for men considering screening include social prompting by partners and clinician recommendations, while barriers include a lack of knowledge, low-risk perception, and masculinity attributes; (4) screening test and algorithm: prostate-specific antigen-based screening reduces PCa-specific mortality and metastatic disease in men aged 55-69 yr at randomisation if screened at least twice; (5) harms and benefits: these benefits come at the cost of unnecessary biopsies, overdiagnosis, and subsequent overtreatment; and (6) future of screening: risk-adapted screening including (prebiopsy) risk calculators, magnetic resonance imaging, and blood- and urine-based biomarkers could reduce these harms. To enable a comprehensive overview, we focused on SRs. These do not include the most recent prospective studies, which were therefore incorporated in the discussion., Conclusions and Clinical Implications: By identifying consistent and conflicting evidence, this review highlights the evidence-based foundations that can be built upon, as well as areas requiring further research and improvement to reduce the burden of PCa in the EU and UK., Patient Summary: This review of 26 reviews covers various aspects of prostate cancer screening such as invitation, decision-making, screening tests, harms, and benefits. This review provides insights into existing evidence, highlighting the areas of consensus and discrepancies, to guide future research and improve prostate cancer screening strategies in Europe., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Previous research quantified the effect of prostate-specific antigen (PSA)-based prostate cancer (PCa) screening on quality-adjusted life years using 11-yr follow-up data from the European Randomized Study of Screening for Prostate Cancer (ERSPC) extrapolated by the Microsimulation Screening Analysis (MISCAN). ERSPC data now matured to 21 yr of follow-up., Objective: To provide an overview of the effect of PSA-based screening on tumour characteristics and PCa treatment using long-term, detailed, empirical ERSPC data., Design, Setting, and Participants: Men were included from the ERSPC Rotterdam who were randomised to a PSA-based screening (S) or control (C) arm., Outcome Measurements and Statistical Analysis: We assessed the effects of PSA-based screening on the number of PCa diagnoses, tumour characteristics, treatments, and cumulative incidence of disease progression. We also evaluated the changes in tumour characteristics and treatments over time for both study arms., Results and Limitations: Among PCa patients in the S-arm, fewer patients were diagnosed with advanced tumour stages (T3/T4: 12% vs 23%; relative risk [RR] = 0.50; 95% confidence interval [CI] 0.44-0.57), less disease progression was observed, and less secondary treatment (30% vs 48%; RR = 0.61; 95% CI 0.57-0.66; p < 0.001) and less palliative treatment were needed (21% vs 55%; RR = 0.38; 95% CI 0.35-0.42) than among those in the C-arm. This was at the cost of overdiagnosis and increased local treatments (eg, radical prostatectomy: 32% vs 14%; RR = 2.18; 95% CI 1.92-2.48). Over time, the number of local treatments decreased, whereas expectant management strategies increased. The RRs of treatments were slightly different from those of the MISCAN., Conclusions: After 21 yr of follow-up, empirical data of the ERSPC showed that PSA-based screening reduces advanced PCa stages, disease progression, and extensive treatments at the cost of more overdiagnosis and probably more overtreatment. Our data showed reduced local treatments and increased expectant management strategies over time., Patient Summary: Prostate-specific antigen-based screening reduces the number of invasive prostate cancer treatments needed, however, at the cost of more overdiagnosis and probably more overtreatment. Limiting these costs remains crucial to benefit optimally from prostate cancer screening., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate whether a subgroup of men can be identified that would benefit more from screening than others., Materials and Methods: This retrospective cohort study was based on three European Randomised Study of Screening for Prostate Cancer (ERSPC) centres, Finland, the Netherlands and Sweden. We identified 126 827 men aged 55-69 years in the study who were followed for maximum of 16 years after randomisation. The primary outcome was prostate cancer (PCa) mortality. We analysed three age groups 55-59, 60-64 and 65-69 years and PCa cases within four European Association of Urology (EAU) risk groups: low, intermediate, high risk, and advanced disease., Results: The hazard ratio (HR) for PCa mortality in the screening arm relative to the control arm for men aged 55-59 years was 0.96 (95% confidence interval [CI] 0.75-1.24) in Finland, 0.70 (95% CI 0.44-1.12) in the Netherlands and 0.42 (95% CI 0.24-0.73) in Sweden. The HR for men aged 60-64 years was 1.03 (95% CI 0.77-1.37) in Finland, 0.76 (95% CI 0.50-1.16) in the Netherlands and 0.97 (95% CI 0.64-1.48) in Sweden. The HR for men aged 65-69 years was 0.80 (95% CI 0.62-1.03) in Finland and 0.57 (95% CI 0.38-0.83) in the Netherlands, and this age group was absent in Sweden. In the EAU risk group analysis, PCa mortality rates were materially lower for men with advanced disease at diagnosis in all three countries: 0.67 (95% CI 0.56-0.82) in Finland, 0.28 (95% CI 0.18-0.44) in the Netherlands, and 0.48 (95% CI 0.30-0.78) in Sweden., Conclusion: We were unable to unequivocally identify the optimal age group for screening, as mortality reduction differed among centres and age groups. Instead, the screening effect appears to depend on screening duration, and the number and frequency of screening rounds. PCa mortality reduction by screening is largely attributable to stage shift., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background and Objective: Active surveillance (AS) has evolved into a widely applied treatment strategy for many men around the world with low-risk prostate cancer (or in selected cases intermediate-risk disease). Here, we report on the safety and acceptability of AS, and treatment outcomes for low- and intermediate-risk tumours over time in 14 623 men with follow-up of over 6 yr., Methods: Clinical data from 26 999 men on AS from 25 cohorts in 15 countries have been collected in an international database from 2000 onwards., Key Findings and Limitations: Across our predefined four time periods of 4 yr each (covering the period 2000-2016), there was no significant change in overall survival (OS). However, metastasis-free survival (MFS) rates have improved since the second period and were excellent (>99%). Treatment-free survival rates for earlier periods showed a slightly more rapid shift to radical treatment. Over time, there was a constant proportion of 5% of men for whom anxiety was registered as the reason for treatment alteration. There was, however, also a subset of 10-15% in whom treatment was changed, for which no apparent reason was available. In a subset of men (10-15%), tumour progression was the trigger for treatment. In men who opted for radical treatment, surgery was the most common treatment modality. In those men who underwent radical treatment, 90% were free from biochemical recurrence at 5 yr after treatment., Conclusions and Clinical Implications: Our study confirms that AS was a safe management option over the full duration in this large multicentre cohort with long-term follow-up, given the 84.1% OS and 99.4% MFS at 10 yr. The probability of treatment at 10 yr was 20% in men with initial low-risk tumours and 31% in men with intermediate-risk tumours. New diagnostic modalities may improve the acceptability of follow-up using individual risk assessments, while safely broadening the use of AS in higher-risk tumours., Patient Summary: Active surveillance (AS) has evolved into a widely applied treatment strategy for many men with prostate cancer around the world. In this report, we show the long-term safety of following AS for men with low- and intermediate-risk prostate cancer. Our study confirms AS as a safe management option for low- and intermediate-risk prostate cancer. New diagnostic modalities may improve the acceptability of follow-up using individual risk assessments, while safely broadening the use of AS in higher-risk tumours., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

In 2022, the European Commission updated its recommendation on cancer screening, inviting the Member States (MSs) to explore the feasibility of stepwise implementation of population-based screening for prostate cancer (PCa). In line with this recommendation, the PRAISE-U (Prostate Cancer Awareness and Initiative for Screening in the European Union (EU)) project was initiated. As part of the PRAISE-U, we aim to understand the current practice towards early detection in the EU MSs, the barriers to implementing or planning population-based screening programmes, and potential solutions to overcome these barriers., Methods: We adapted the Barriers to Effective Screening Tool (BEST) survey to the PCa context. However, it has not been validated in this context. We translated it into all spoken languages in the EU27 and disseminated it to different stakeholders across the EU using a snowballing approach., Results: We received 410 responses from 55 countries, of which 301 (73%) were from the 27 EU MSs. The most represented stakeholder group was urologists (218 (54%)), followed by general practitioners (GPs) (83 (21%)), patient representatives (35 (9%)), policy stakeholders (27 (7%)), researchers (23 (6%)), oncologists, pathologists, radiologists, nurses, and others (16 (4%)) and one industry representative. Among all respondents, 286 (69%) reported the absence of a population-based screening programme, mainly attributed to resource limitations and a lack of political and medical society support. Out of these 286 respondents, 196 (69%) indicated that opportunistic screening is being applied in their country, and 199 (70%) expressed their support for population-based screening programmes (which was highest amongst patient representatives and urologists and lowest amongst GPs and policy stakeholders). The highest scored barriers were lack of political support, insufficient operational resources, and inadequate participation. Suggested solutions to overcome these included awareness campaigns, consensus meetings, political lobbying and European guidelines (to overcome political support barriers), compatible IT systems (to overcome operational barriers), and easy access (to overcome participation barriers)., Conclusions: Participants have noted the presence of opportunistic screening, and particularly urologists and patient representatives expressed their support for the establishment of a population-based PCa screening programme. Nevertheless, successful implementation of population-based screening programmes is complex; it requires political and medical society support, operational resources and capacity, awareness campaigns, as well as the development of protocols, guidelines, and legal frameworks.

Background: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics., Objective: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data., Design, Setting, and Participants: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146)., Outcome Measurements and Statistical Analysis: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data., Results and Limitations: The most common comorbidities were hypertension (35-73%), obesity (9.2-54%), and type 2 diabetes (11-28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12-25%) and emergency department visits (10-14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent., Conclusions: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data., Patient Summary: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objective: The treatment landscape of metastatic prostate cancer (mPCa) has evolved significantly over the past two decades. Despite this, the optimal therapy for patients with mPCa has not been determined. This systematic review identifies available predictive models that assess mPCa patients' response to treatment., Methods: We critically reviewed MEDLINE and CENTRAL in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Only quantitative studies in English were included with no time restrictions. The quality of the included studies was assessed using the PROBAST tool. Data were extracted following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews criteria., Key Findings and Limitations: The search identified 616 citations, of which 15 studies were included in our review. Nine of the included studies were validated internally or externally. Only one study had a low risk of bias and a low risk concerning applicability. Many studies failed to detail model performance adequately, resulting in a high risk of bias. Where reported, the models indicated good or excellent performance., Conclusions and Clinical Implications: Most of the identified predictive models require additional evaluation and validation in properly designed studies before these can be implemented in clinical practice to assist with treatment decision-making for men with mPCa., Patient Summary: In this review, we evaluate studies that predict which treatments will work best for which metastatic prostate cancer patients. We found that existing studies need further improvement before these can be used by health care professionals., (© 2024 The Author(s).)

Purpose: External validation of existing risk calculators (RC) to assess the individualized risk of detecting prostate cancer (PCa) in prostate biopsies is needed to determine their clinical usefulness. The objective was to externally validate the Rotterdam Prostate Cancer RCs 3 and 4 (RPCRC-3/4) and that incorporating PHI (RPCRC-PHI) in a contemporary Spanish cohort., Methods: Multicenter prospective study that included patients suspicious of harboring PCa. Men who attended the urology consultation were tested for PHI before prostate biopsy. To evaluate the performance of the prediction models: discrimination (receiver operating characteristic (ROC) curves), calibration and net benefit [decision curve analysis (DCA)] were calculated. These analyses were carried out for detection of any PCa and clinically significant (cs)PCa, defined as ISUP grade ≥ 2., Results: Among the 559 men included, 337 (60.28%) and 194 (34.7%) were diagnosed of PCa and csPCa, respectively. RPCRC-PHI had the best discrimination ability for detection of PCa and csPCa with AUCs of 0.85 (95%CI 0.82-0.88) and 0.82 (95%CI 0.78-0.85), respectively. Calibration plots showed that RPCRC-3/4 underestimates the risk of detecting PCa showing the need for recalibration. In DCA, RPCRC-PHI shows the highest net benefit compared to biopsy all men., Conclusions: The RPCRC-PHI performed properly in a contemporary clinical setting, especially for prediction of csPCa., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Magnetic resonance imaging (MRI)-based risk calculators can replace or augment traditional prostate cancer (PCa) risk prediction tools. However, few data are available comparing performance of different MRI-based risk calculators in external cohorts across different countries or screening paradigms., Objective: To externally validate and compare MRI-based PCa risk calculators (Prospective Loyola University Multiparametric MRI [PLUM], UCLA [University of California, Los Angeles]-Cornell, Van Leeuwen, and Rotterdam Prostate Cancer Risk Calculator-MRI [RPCRC-MRI]) in cohorts from Europe and North America., Design, Setting, and Participants: This multi-institutional, external validation diagnostic study of 3 unique cohorts was performed from January 1, 2015, to December 31, 2022. Two cohorts from Europe and North America used MRI before biopsy, while a third cohort used an advanced serum biomarker, the Prostate Health Index (PHI), before MRI or biopsy. Participants included adult men without a PCa diagnosis receiving MRI before prostate biopsy., Interventions: Prostate MRI followed by prostate biopsy., Main Outcomes and Measures: The primary outcome was diagnosis of clinically significant PCa (grade group ≥2). Receiver operating characteristics for area under the curve (AUC) estimates, calibration plots, and decision curve analysis were evaluated., Results: A total of 2181 patients across the 3 cohorts were included, with a median age of 65 (IQR, 58-70) years and a median prostate-specific antigen level of 5.92 (IQR, 4.32-8.94) ng/mL. All models had good diagnostic discrimination in the European cohort, with AUCs of 0.90 for the PLUM (95% CI, 0.86-0.93), UCLA-Cornell (95% CI, 0.86-0.93), Van Leeuwen (95% CI, 0.87-0.93), and RPCRC-MRI (95% CI, 0.86-0.93) models. All models had good discrimination in the North American cohort, with an AUC of 0.85 (95% CI, 0.80-0.89) for PLUM and AUCs of 0.83 for the UCLA-Cornell (95% CI, 0.80-0.88), Van Leeuwen (95% CI, 0.79-0.88), and RPCRC-MRI (95% CI, 0.78-0.87) models, with somewhat better calibration for the RPCRC-MRI and PLUM models. In the PHI cohort, all models were prone to underestimate clinically significant PCa risk, with best calibration and discrimination for the UCLA-Cornell (AUC, 0.83 [95% CI, 0.81-0.85]) model, followed by the PLUM model (AUC, 0.82 [95% CI, 0.80-0.84]). The Van Leeuwen model was poorly calibrated in all 3 cohorts. On decision curve analysis, all models provided similar net benefit in the European cohort, with higher benefit for the PLUM and RPCRC-MRI models at a threshold greater than 22% in the North American cohort. The UCLA-Cornell model demonstrated highest net benefit in the PHI cohort., Conclusions and Relevance: In this external validation study of patients receiving MRI and prostate biopsy, the results support the use of the PLUM or RPCRC-MRI models in MRI-based screening pathways regardless of European or North American setting. However, tools specific to screening pathways incorporating advanced biomarkers as reflex tests are needed due to underprediction.

Objectives: To compare the performance of currently available biopsy decision support tools incorporating magnetic resonance imaging (MRI) findings in predicting clinically significant prostate cancer (csPCa)., Patients and Methods: We retrospectively included men who underwent prostate MRI and subsequent targeted and/or systematic prostate biopsies in two large European centres. Available decision support tools were identified by a PubMed search. Performance was assessed by calibration, discrimination, decision curve analysis (DCA) and numbers of biopsies avoided vs csPCa cases missed, before and after recalibration, at risk thresholds of 5%-20%., Results: A total of 940 men were included, 507 (54%) had csPCa. The median (interquartile range) age, prostate-specific antigen (PSA) level, and PSA density (PSAD) were 68 (63-72) years, 9 (7-15) ng/mL, and 0.20 (0.13-0.32) ng/mL 2 , respectively. In all, 18 multivariable risk calculators (MRI-RCs) and dichotomous biopsy decision strategies based on MRI findings and PSAD thresholds were assessed. The Van Leeuwen model and the Rotterdam Prostate Cancer Risk Calculator (RPCRC) had the best discriminative ability (area under the receiver operating characteristic curve 0.86) of the MRI-RCs that could be assessed in the whole cohort. DCA showed the highest clinical utility for the Van Leeuwen model, followed by the RPCRC. At the 10% threshold the Van Leeuwen model would avoid 22% of biopsies, missing 1.8% of csPCa, whilst the RPCRC would avoid 20% of biopsies, missing 2.6% of csPCas. These multivariable models outperformed all dichotomous decision strategies based only on MRI-findings and PSAD., Conclusions: Even in this high-risk cohort, biopsy decision support tools would avoid many prostate biopsies, whilst missing very few csPCa cases. The Van Leeuwen model had the highest clinical utility, followed by the RPCRC. These multivariable MRI-RCs outperformed and should be favoured over decision strategies based only on MRI and PSAD., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background and Objective: The ability of health care professionals to communicate with patients compassionately and effectively is crucial for shared decision-making, but little research has investigated patient-clinician communication. As part of PIONEER-an international Big Data Consortium led by the European Association of Urology to answer key questions for men with prostate cancer (PCa), funded through the IMI2 Joint Undertaking under grant agreement 777492- we investigated communication between men diagnosed with PCa and the health care professional(s) treating them across Europe., Methods: We used the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Communication 26, which was shared via the PIONEER and patient organisations on March 11, 2022. We sought men who spoke French, Italian, Spanish, German, Dutch, or English who were diagnosed with PCa and were undergoing or had already received treatment for their PCa., Results and Limitations: A total of 372 men reported that they communicated with their clinician during either the diagnostic or the treatment period. Overall, the majority of participants reported positive experiences. However, important opportunities to enhance communication were identified, particularly with regard to correcting misunderstandings, understanding the patient's preferred approach to information presentation, addressing challenging questions, supporting the patient's comprehension of information, attending to the patient's emotional needs, and assessing what information had already been given to patients about their disease and treatment, and how much of it was understood., Conclusions and Clinical Implications: These results help us to identify gaps and barriers to shared treatment decision making. This knowledge will help devise measures to improve patient-health care professional communication in the PCa setting., Patient Summary: As part of the PIONEER initiative, we investigated the communication between men diagnosed with prostate cancer and their health care professionals across Europe. A total of 372 men from six different countries participated in the study. Most participants reported positive experiences, but areas where communication could be improved were identified. These included addressing misunderstandings, tailoring the presentation of information to the patient's preferences, handling difficult questions, supporting emotional needs, and assessing the patient's understanding of their diagnosis and treatment., (© 2024 The Author(s).)

Background and Objective: The possible negative impact of radical surgery on patients' health-related quality of life (HRQoL) plays an important role in preoperative counseling. Here, we analyzed the HRQoL of patients treated for upper urinary tract urothelial carcinoma (UTUC) in the context of a single-arm phase 2 multicenter study, in which the safety and efficacy of a single preoperative intravesical instillation with mitomycin C were investigated. Our objective was to investigate early changes in HRQoL in patients undergoing radical surgery for UTUC and identify factors associated with these outcomes., Methods: Patients with pTanyN0-1M0 UTUC were prospectively included. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) questionnaire at baseline, and at 1 and 3 mo after surgery. A linear mixed model was used to evaluate the changes in HRQoL over time and identify the variables associated with these outcomes. The clinical effect size was used to assess the clinical impact and level of perceptibility of HRQoL changes for clinicians and/or patients based on given thresholds., Key Findings and Limitations: Between 2017 and 2020, 186 patients were included. At baseline, 1 mo after surgery, and 3 mo after surgery, response rates were 91%, 84%, and 78%, respectively. One month after surgery, a statistically significant and clinically relevant deterioration was observed in physical, role, and social functioning, and for the included symptom scales: constipation, fatigue, and pain. An improvement in emotional functioning was observed. At 3 mo, HRQoL returned to baseline levels, except emotional functioning, which improved at 1 mo and persisted to be better than that before surgery. Age >70 yr was associated with worse physical functioning, but better social and emotional functioning. Male patients reported better emotional functioning than females. Postoperative complications were negatively associated with social functioning., Conclusions and Clinical Implications: UTUC patients treated with radical surgery experienced a significant, albeit temporary, decline in HRQoL. Three months following surgery, HRQoL outcomes returned to baseline levels. This information can be used to counsel UTUC patients before undergoing radical surgery and contextualize recovery after surgery., Patient Summary: We investigated the changes in quality of life as reported by patients who underwent surgery for upper tract urothelial carcinoma (UTUC). We found that patients experienced a decline in quality of life 1 mo after surgery, but this was temporary, with full recovery of quality of life 3 mo after surgery. These findings can help doctors and other medical staff in counseling UTUC patients before undergoing radical surgery., (© 2023 The Author(s).)

Background: The optimal timing for discontinuing screening of prostate cancer (PCa) in elderly men is currently not known and remains debated., Objective: To assess prostate cancer-specific mortality (PCSM) in elderly men who previously underwent prostate-specific antigen (PSA)-based screening and to identify those who may benefit from continued screening., Design, Setting, and Participants: A total of 7052 men, who participated in the screening arm of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer and were aged 70-74 yr at their last screening visit after undergoing a maximum of three screening rounds without being diagnosed with PCa, were included., Outcome Measurements and Statistical Analysis: The cumulative incidence of PCSM by the age of 85 yr was assessed. Additionally, a competing risk regression was performed to assess the potential predictors of PCSM., Results and Limitations: The median follow-up was 16 yr. The cumulative incidence of PCSM by the age of 85 yr was 0.54% (95% confidence interval [CI]: 0.40-0.70) in all men, 0.11% (95% CI: 0.05-0.27) in men with PSA <2 ng/ml, 0.85% (95% CI: 0.47-1.5) in men with PSA 2-3 ng/ml, and 6.8% (95% CI: 3.1-15) in men with PSA ≥6.5 ng/ml and no previous benign biopsy. PSA (subdistribution hazard ratio [sHR]: 2.0; 95% CI: 1.7-2.3), previous benign prostate biopsy (sHR: 0.41; 95% CI: 0.23-0.72), and hypertension (sHR: 0.48; 95% CI: 0.25-0.91) were significantly associated with PCSM., Conclusions: Men aged 70-74 yr who have previously undergone PSA-based screening without receiving a PCa diagnosis have a very low risk of dying from PCa by the age of 85 yr. These data suggest that screening may be discontinued in men with PSA <3.0 ng/ml or previous benign prostate biopsies. Those with higher PSA levels and no prior biopsies may consider continued screening if life expectancy exceeds 10 yr., Patient Summary: This study shows that men who participated in a prostate cancer screening trial have a very low risk of dying from prostate cancer if they have not been diagnosed with prostate cancer by the age of 74 yr., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cancer survivorship was recently identified as a prostate cancer (PCa) research priority by PIONEER, a European network of excellence for big data in PCa. Despite being a research priority, cancer survivorship lacks a clear and agreed definition, and there is a distinct paucity of patient-reported outcome (PRO) data available on the subject. Data collection on cancer survivorship depends on the availability and implementation of (validated) routinely collected patient-reported outcome measures (PROMs). There have been recent advances in the availability of such PROMs. For instance, the European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) is developing survivorship questionnaires. This provides an excellent first step in improving the data available on cancer survivorship. However, we propose that an agreed, standardised definition of (prostate) cancer survivorship must first be established. Only then can real-world data on survivorship be collected to strengthen our knowledge base. With more men than ever surviving PCa, this type of research is imperative to ensure that the quality of life of these men is considered as much as their quantity of life., Patient Summary: As there are more prostate cancer survivors than ever before, research into cancer survivorship is crucial. We highlight the importance of such research and provide recommendations on how to carry it out. The first step should be establishing agreement on a standardised definition of survivorship. From this, patient-reported outcome measures can then be used to collect important survivorship data., (© 2023 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology.)

Background: To further strengthen the voice of patients, Europa Uomo initiated the Europa Uomo Patient Reported Outcome Study 2.0 (EUPROMS 2.0) in October 2021., Objective: To collect the self-reported perspective of prostate cancer (PCa) patients on physical and mental well-being after PCa treatment outside a clinical trial setting to inform future fellow patients about the impact of PCa treatment., Design, Setting, and Participants: Europa Uomo invited PCa patients to complete a cross-sectional survey including the validated EQ-5D-5L, EORTC-QLQ-C30, and the EPIC-26 questionnaires. Furthermore, the nine-item Shared Decision Making Questionnaire (SDM-Q-9) and diagnostic clinical scenarios were included., Outcome Measurements and Statistical Analysis: Descriptive statistics was used to assess the demographic and clinical characteristics and to analyze the patient-reported outcome data., Results and Limitations: Between October 25, 2021 and January 17, 2022, 3571 men from 30 countries completed the EUPROMS 2.0 survey. The median age of respondents was 70 yr (interquartile range 65-75 yr). Half of the respondents underwent one treatment, most often radical prostatectomy. Men who are treated actively experience lower health-related quality of life than men on active surveillance, mainly regarding sexual function, fatigue, and insomnia. Lower urinary incontinence levels were seen for men who underwent radical prostatectomy (single treatment or in combination with other treatments). Of the respondents, 42% indicated that the determination of the prostate-specific antigen (PSA) value was part of a routine blood test; 25% wanted to undergo screening/early detection for PCa, and 20% indicated that the determination of the PSA value had a clinical reason., Conclusions: A large sample of 3571 international patients has contributed patient experience after PCa treatment in the EUPROMS 2.0 study, confirming that treatment for PCa mainly affects urinary incontinence, sexual function, fatigue, and insomnia. Such information can be used to direct toward a better patient-doctor relationship, to offer patients ready access to responsible information and a better understanding of their disease and treatment., Patient Summary: Through the EUPROMS 2.0 survey, Europa Uomo has strengthened the voice of the patient. Such information can be used to inform future prostate cancer (PCa) patients about the impact of PCa treatment and to engage them in informed and shared decision-making., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The European Association of Urology guidelines recommend a risk-based strategy for prostate cancer screening based on the first prostate-specific antigen (PSA) level and age., Objective: To analyze the impact of the first PSA level on prostate cancer (PCa) detection and PCa-specific mortality (PCSM) in a population-based screening trial (repeat screening every 2-4 yr)., Design, Setting, and Participants: We evaluated 25589 men aged 55-59 yr, 16898 men aged 60-64 yr, and 12936 men aged 65-69 yr who attended at least one screening visit in the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial (screening arm: repeat PSA testing every 2-4 yr and biopsy in cases with elevated PSA; control arm: no active screening offered) during 16-yr follow-up (FU)., Outcome Measurements and Statistical Analysis: We assessed the actuarial probability for any PCa and for clinically significant (cs)PCa (Gleason ≥7). Cox proportional-hazards regression was performed to assess whether the association between baseline PSA and PCSM was comparable for all age groups. A Lorenz curve was computed to assess the association between baseline PSA and PCSM for men aged 60-61 yr., Results and Limitations: The overall actuarial probability at 16 yr ranged from 12% to 16% for any PCa and from 3.7% to 5.7% for csPCa across the age groups. The actuarial probability of csPCa at 16 yr ranged from 1.2-1.5% for men with PSA <1.0 ng/ml to 13.3-13.8% for men with PSA ≥3.0 ng/ml. The association between baseline PSA and PCSM differed marginally among the three age groups. A Lorenz curve for men aged 60-61 yr showed that 92% of lethal PCa cases occurred among those with PSA above the median (1.21 ng/ml). In addition, for men initially screened at age 60-61 yr with baseline PSA <2 ng/ml, further continuation of screening is unlikely to be beneficial after the age of 68-70 yr if PSA is still <2 ng/ml. No case of PCSM emerged in the subsequent 8 yr (up to age 76-78 yr). A limitation is that these results may not be generalizable to an opportunistic screening setting or to contemporary clinical practice., Conclusions: In all age groups, baseline PSA can guide decisions on the repeat screening interval. Baseline PSA of <1.0 ng/ml for men aged 55-69 yr is a strong indicator to delay or stop further screening., Patient Summary: In prostate cancer screening, the patient's baseline PSA (prostate-specific antigen) level can be used to guide decisions on when to repeat screening. The PSA test when used according to current knowledge is valuable in helping to reduce the burden of prostate cancer., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Considering the long natural history of prostate cancer (PCa), long-term results of the European Randomised Study of Screening for PCa (ERSPC) are crucial., Objective: To provide an update on the effect of prostate-specific antigen (PSA)-based screening on PCa-specific mortality (PCSM), metastatic disease, and overdiagnosis in the Dutch arm of the ERSPC., Design, Setting, and Participants: Between 1993 and 2000, a total of 42376 men, aged 55-74 yr, were randomised to a screening or a control arm. The main analysis was performed with men aged 55-69 yr (n = 34831). Men in the screening arm were offered PSA-based screening with an interval of 4 yr., Outcome Measurements and Statistical Analysis: Intention-to-screen analyses with Poisson regression were used to calculate rate ratios (RRs) of PCSM and metastatic PCa., Results and Limitations: After a median follow-up of 21 yr, the RR of PCSM was 0.73 (95% confidence interval [CI]: 0.61-0.88) favouring screening. The numbers of men needed to invite (NNI) and needed to diagnose (NND) to prevent one PCa death were 246 and 14, respectively. For metastatic PCa, the RR was 0.67 (95% CI: 0.58-0.78) favouring screening. The NNI and NND to prevent one metastasis were 121 and 7, respectively. No statistical difference in PCSM (RR of 1.18 [95% CI: 0.87-1.62]) was observed in men aged ≥70 yr at the time of randomisation. In the screening arm, higher rates of PCSM and metastatic disease were observed in men who were screened only once and in a selected group of men above the screening age cut-off of 74 yr., Conclusions: The current analysis illustrates that with a follow-up of 21 yr, both absolute metastasis and mortality reduction continue to increase, resulting in a more favourable harm-benefit ratio than demonstrated previously. These data do not support starting screening at the age of 70-74 yr and show that repeated screening is essential., Patient Summary: Prostate-specific antigen-based prostate cancer screening reduces metastasis and mortality. Longer follow-up shows fewer invitations and diagnoses needed to prevent one death, a positive note towards the issue of overdiagnosis., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Importance: Stratifying patients with biochemical recurrence (BCR) after primary treatment for prostate cancer based on the risk of prostate cancer-specific mortality (PCSM) is essential for determining the need for further testing and treatments., Objective: To evaluate the association of BCR after radical prostatectomy or radiotherapy and its current risk stratification with PCSM., Design, Setting, and Participants: This population-based cohort study included a total of 16 311 male patients with 10 364 (64%) undergoing radical prostatectomy and 5947 (36%) undergoing radiotherapy with curative intent (cT1-3, cM0) and PSA follow-up in Stockholm, Sweden, between 2003 and 2019. Follow-up for all patients was until death, emigration, or end of the study (ie, December 31, 2018). Data were analyzed between September 2022 and March 2023., Main Outcomes and Measures: Primary outcomes of the study were the cumulative incidence of BCR and PCSM. Patients with BCR were stratified in low- and high-risk according to European Association of Urology (EAU) criteria., Exposures: Radical prostatectomy or radiotherapy., Results: A total of 16 311 patients were included. Median (IQR) age was 64 (59-68) years in the radical prostatectomy cohort (10 364 patients) and 69 (64-73) years in the radiotherapy cohort (5947 patients). Median (IQR) follow-up for survivors was 88 (55-138) months and 89 (53-134) months, respectively. Following radical prostatectomy, the 15-year cumulative incidences of BCR were 16% (95% CI, 15%-18%) for the 4024 patients in the low D'Amico risk group, 30% (95% CI, 27%-32%) for the 5239 patients in the intermediate D'Amico risk group, and 46% (95% CI, 42%-51%) for 1101 patients in the high D'Amico risk group. Following radiotherapy, the 15-year cumulative incidences of BCR were 18% (95% CI, 15%-21%) for the 1230 patients in the low-risk group, 24% (95% CI, 21%-26%) for the 2355 patients in the intermediate-risk group, and 36% (95% CI, 33%-39%) for the 2362 patients in the high-risk group. The 10-year cumulative incidences of PCSM after radical prostatectomy were 4% (95% CI, 2%-6%) for the 1101 patients who developed low-risk EAU-BCR and 9% (95% CI, 5%-13%) for 649 patients who developed high-risk EAU-BCR. After radiotherapy, the 10-year PCSM cumulative incidences were 24% (95% CI, 19%-29%) for the 591 patients in the low-risk EAU-BCR category and 46% (95% CI, 40%-51%) for the 600 patients in the high-risk EAU-BCR category., Conclusions and Relevance: These findings suggest the validity of EAU-BCR stratification system. However, while the risk of dying from prostate cancer in low-risk EAU-BCR after radical prostatectomy was very low, patients who developed low-risk EAU-BCR after radiotherapy had a nonnegligible risk of prostate cancer mortality. Improving risk stratification of patients with BCR is pivotal to guide salvage treatment decisions, reduce overtreatment, and limit the number of staging tests in the event of PSA elevations after primary treatment.

Background: Nerve-sparing (NS) radical prostatectomy (RP) results in better functional outcomes. Intraoperative neurovascular structure-adjacent frozen section examination (NeuroSAFE) significantly increases the frequency of NS surgery. The effect of NeuroSAFE on postoperative erectile function (EF) and continence is not yet clear., Objective: To describe EF and continence outcomes for men undergoing RP with the NeuroSAFE technique., Design, Setting, and Participants: Between September 2018 and February 2021, 1034 men underwent robot-assisted RP. Data for patient-reported outcomes were collected via validated questionnaires., Intervention: NeuroSAFE technique for RP., Outcome Measurements and Statistical Analysis: Continence was assessed using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) or Expanded Prostate Cancer Index Composite short form (EPIC-26) and defined as use of 0-1 pads/d. EF was evaluated using EPIC-26 or the International Index of Erectile Function short form (IIEF-5), with data converted according to the Vertosick method and categorized. Descriptive statistics were used to asses and describe tumor characteristics and continence and EF outcomes., Results and Limitations: Of the 1034 men who underwent RP after introduction of the NeuroSAFE technique, 63% and 60% completed a preoperative and at least one postoperative questionnaire on continence and EF, respectively. Of the men who underwent unilateral or bilateral NS surgery, use of 0-1 pads/d was reported by 93% after 1 yr and 96% after 2 yr; the corresponding rates for men who underwent non-NS surgery were 86% and 78%. Overall, use of 0-1 pads/d was reported by 92% of the men at 1 yr and by 94% at 2 yr after RP. Men in the NS group had a good or intermediate Vertosick score after RP more often than the non-NS group. Overall, 44% of the men had a good or intermediate Vertosick score at 1 and 2 yr after RP., Conclusions: After introduction of the NeuroSAFE technique, the continence rate was 92% at 1 yr and 94% at 2 yr after RP. The NS group had a greater percentage of men with an intermediate or good Vertosick score and a higher continence rate after RP in comparison to the non-NS group., Patient Summary: Our study shows that after introduction of the NeuroSAFE technique during removal of the prostate, the continence rate among patients was 92% at 1 year and 94% at 2 years after surgery. Some 44% of the men had a good or intermediate score for erectile function 1 and 2 years after surgery., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Currently, transperineal prostate biopsy (TPB) is preferred over transrectal biopsy (TRB) because of less infectious complications and improved clinically significant prostate cancer (csPCa) detection. However, literature on omitting antibiotic prophylaxis (AP) is limited. Furthermore, previous studies did not include invasive cribriform growth/intraductal carcinoma (CR/IDC) in the definition of csPCa. Therefore, we compared the infectious complication rates between TPB without AP and TRB with AP, and we compared the csPCa detection rates between TPB and TRB including CR/IDC in the definition of csPCa., Methods: We included 729 men who were referred to Erasmus MC Cancer Institute between 2013-2019 for MRI/TRUS fusion-guided prostate biopsy. Up to 2019, TRB was performed with AP, thereafter TPB was performed without AP. Data on complications were collected prospectively. We compared csPCa detection rates between the biopsy routes using multivariable logistic regressions for men without previous PCa diagnosis and mixed logistic regression for men on active surveillance. To compare the csPCa detection rates in anterior and apical lesions, and the complications rates between the biopsy routes, we used the chi-square test., Results: Overall, we found no difference in csPCa detection between TPB and TRB (odds ratio 1.0, 95%-confidence interval (CI) 0.62-1.76, p = 0.9; for men on active surveillance: odds ratio 1.05, 95%-CI 0.58-1.88, p = 0.9). This was confirmed in anterior and apical lesions although absolute numbers were low. TPB reduced infectious complications with fever compared to TRB (1.1% vs 5.1%, difference = 4.0%, 95%-CI 1.0-7.9, p = 0.010)., Conclusions: TPB has no different csPCa detection rate from TRB taking CR/IDC into account. TPB is, however, preferable because of less infectious complications, even if AP is omitted., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Aims: Radical prostatectomy (RP) for prostate cancer is frequently complicated by erectile dysfunction and urinary incontinence. However, sparing of the nerve bundles adjacent to the posterolateral sides of the prostate reduces the number of complications at the risk of positive surgical margins. Preoperative selection of men eligible for safe, nerve-sparing surgery is therefore needed. Our aim was to identify pathological factors associated with positive posterolateral surgical margins in men undergoing bilateral nerve-sparing RP., Methods and Results: Prostate cancer patients undergoing RP with standardised intra-operative surgical margin assessment according to the NeuroSAFE technique were included. Preoperative biopsies were reviewed for grade group (GG), cribriform and/or intraductal carcinoma (CR/IDC), perineural invasion (PNI), cumulative tumour length and extraprostatic extension (EPE). Of 624 included patients, 573 (91.8%) received NeuroSAFE bilaterally and 51 (8.2%) unilaterally, resulting in a total of 1197 intraoperative posterolateral surgical margin assessments. Side-specific biopsy findings were correlated to ipsilateral NeuroSAFE outcome. Higher biopsy GG, CR/IDC, PNI, EPE, number of positive biopsies and cumulative tumour length were all associated with positive posterolateral margins. In multivariable bivariate logistic regression, ipsilateral PNI [odds ratio (OR) = 2.98, 95% confidence interval (CI) = 1.62-5.48; P < 0.001] and percentage of positive cores (OR = 1.18, 95% CI = 1.08-1.29; P < 0.001) were significant predictors for a positive posterolateral margin, while GG and CR/IDC were not., Conclusions: Ipsilateral PNI and percentage of positive cores were significant predictors for a positive posterolateral surgical margin at RP. Biopsy PNI and tumour volume can therefore support clinical decision-making on the level of nerve-sparing surgery in prostate cancer patients., (© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Background and Objective: Active surveillance (AS) has been established as an important treatment option for patients with localised prostate cancer (PCa). Current evidence suggests that health literacy is an important facilitator or barrier to choosing and adhering to AS. We aim to understand how the level of health literacy has an impact on choosing and adhering to AS for PCa patients., Methods: We performed a narrative literature review in accordance with the Narrative Review guidelines through the MEDLINE online database via PubMed using two different search strategies to identify the relevant literature. We looked at literature until August 2022. A narrative synthesis was performed to identify if there is any evidence on how studies report health literacy as an outcome in the AS population and if there are any interventions targeting health literacy., Key Content and Findings: We identified 18 studies which looked at health literacy in the PCa context. Health literacy was measured in the context of comprehension of information of patients across PCa stages, decision making across PCa stages and quality of life (QoL) across PCa stages. Lower health literacy had a negative impact on the identified themes. Nine of the identified studies used validated health literacy measures. Interventions targeting health literacy have been used to improve health literacy with a positive impact across the patient journey., Conclusions: Health literacy plays an important role in enabling men to take an active part in their treatment journey. In this review, we presented how health literacy is measured and which interventions targeting health literacy are implemented across PCa. These examples of interventions targeting health literacy should be studied further and translated into the AS setting to improve treatment decision making and adherence to AS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-732/coif). MJR serves as an unpaid Associate Editor-in-Chief of Translational Andrology and Urology from January 2020 to December 2023. The other authors have no conflicts of interest to declare., (2023 Translational Andrology and Urology. All rights reserved.)

Objective: To evaluate the feasibility of multivariable risk stratification for early prostate cancer (PCa) detection in a primary healthcare diagnostic facility with regard to its effects on the referral rate and subsequent PCa diagnoses compared to a PSA threshold of 3.0 ng/mL as the current referral indicator., Patients and Methods: In 2014, the Erasmus MC Cancer Institute and the primary healthcare diagnostic facility STAR-SHL (located in Rotterdam city centre) initiated this observational study, in which general practitioners (GPs) could refer men who wished to undergo PCa screening to STAR-SHL for consultation by specially trained personnel. Referral recommendations to secondary healthcare were based on the outcome of application of the Rotterdam Prostate Cancer Risk Calculator (RPCRC) and were compared to the current Dutch GPs' PSA referral threshold of 3.0 ng/mL. For data collection on PCa diagnoses, the study cohort was linked to the Dutch nationwide pathology databank (PALGA)., Results: Between January 2014 and February 2021, 507 men were referred for consultation and in 495 men prostate-specific antigen (PSA) was tested. The median (interquartile range) follow-up from consultation to PALGA linkage was 43 (25-65) months. In total, 279 men (56%) had a PSA level ≥3.0 ng/mL, of whom 68% (95% confidence interval [95% CI] 63-74) were considered at low risk according to the RPCRC. Within 1 year after consultation, one of these men (0.52%; 95% CI 0.092-2.9) was diagnosed with clinically significant (cs)PCa (i.e., International Society of Urological Pathology Grade Group ≥2). Thereafter, another four (2.1%; 95% CI 0.82-5.3) low-risk men were diagnosed with csPCa. Of the high-risk men who were biopsied within 1 year after consultation (n = 61), 77% (95% CI 65-86) were diagnosed with PCa and 49% (95% CI 37-61) with csPCa., Conclusion: In a primary healthcare diagnostic facility, the RPCRC could reduce up to 68% of referrals to secondary healthcare, as compared to a PSA referral threshold of 3.0 ng/mL. Deploying the RPCRC in this setting resulted in a high csPCa detection rate in those men biopsied. This strategy can be considered safe since the observational data showed low proportions of csPCa among men at low risk., (© 2022 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: We aimed to quantify the difference in patient reported outcome (PRO) data between clinical studies and the (patient initiated) EUPROMS study for sexual functioning and urinary incontinence after radical prostatectomy (RP) and external beam radiotherapy (RT)., Methods: Europa Uomo, the patient organization of men with prostate cancer (PCa) in Europe, initiated the EUPROMS study. Data involved 1101 men with PCa treated with RP and 304 patients treated with RT. In a literature search we identified investigator-initiated studies which matched EUPROMS characteristics. The observed scores in the literature were compared to the scores calculated using the EUPROMS-models. Data from EUPROMS was used to develop four regression models for men treated with RP and RT., Results: The time between diagnosis and questionnaire completion was estimated to be 3/4 years for men after RP, and 5 for RT. Eight studies were identified which reported PRO data using the EPIC with comparable follow-up. Large heterogeneity was observed in reported literature. For sexual function, the difference in calculated and observed scores is at most 24 points (range 3-24 points) and differences between studies were less evident; for urinary incontinence, the difference between calculated and observed scores is at most 15 points (range 1.5-15) (4 scores above the MID) and previous studies underreported the actual effect compared to the current study., Conclusions: Previous clinical investigator studies underreported the actual effect for urinary incontinence compared to the EUPROMS study. Clinicians should be aware of a potential underestimation of the reported PRO in the patient-physician communication.

Background: The ERSPC study has demonstrated that prostate-specific antigen (PSA)-based screening results in a relative increase in diagnosis of (low-risk) prostate cancer (PCa) and a reduction in metastatic disease and PCa mortality., Objective: To evaluate the burden of PCa among men randomized to active screening compared to those in the control arm in ERSPC Rotterdam., Design Setting and Participants: We analyzed data for participants in the Dutch section of the ERSPC, including 21 169 men randomized to the screening arm and 21 136 randomized to the control arm. Men in the screening arm were invited for PSA-based screening every 4 yr, and transrectal ultrasound-guided prostate biopsy was recommended for those with PSA ≥3.0 ng/ml., Outcome Measurements and Statistical Analysis: We analyzed detailed follow-up and mortality data up to January 1, 2019, to a maximum of 21 yr, using multistate models., Results and Limitations: At 21 yr, 3046 men (14%) had been diagnosed with nonmetastatic PCa and 161 (0.76%) with metastatic PCa in the screening arm. In the control arm, 1698 men (8.0%) had been diagnosed with nonmetastatic PCa and 346 (1.6%) with metastatic PCa. In comparison to the control arm, men in the screening arm were diagnosed with PCa almost 1 yr earlier and if diagnosed with nonmetastatic PCa lived on average for almost 1 yr longer without disease progression. Among those who experienced biochemical recurrence (18-19% after nonmetastatic PCa), progression to metastatic disease or death was quicker in the control arm: men in the screening arm lived for 7.17 yr without progression, while the progression-free interval was only 1.59 yr for men in the control arm over a 10-yr time period. Among those who experienced metastatic disease, men in both study arms lived for 5 yr over a 10-yr time period., Conclusions: PCa diagnosis was earlier after study entry for men in the PSA-based screening arm. However, disease progression was not as fast in the screening arm as in the control arm: once men in the control arm experienced biochemical recurrence, progression to metastatic disease or death was 5.6 yr faster than in the screening arm. Our results confirm the ability of early disease detection to reduce suffering and death from PCa at the cost of earlier (and more frequent) treatment-induced reductions in quality of life., Patient Summary: Our study shows that early detection of prostate cancer can reduce suffering and death from this disease. However, screening based on measurement of prostate-specific antigen (PSA) can also result in an earlier treatment-induced reduction in quality of life., (© 2023 The Authors.)

Pre-clinical studies have suggested sex hormone signalling pathways may influence tumorigenesis in neuroendocrine neoplasia (NEN). We conducted a retrospective, population-based study to compare overall survival (OS) between males and females with NEN. A total of 14,834 cases of NEN diagnosed between 2012 and 2018, recorded in England's National Cancer Registry and Analysis Service (NCRAS), were analysed. The primary outcome was OS with 5 years maximum follow-up. Multivariable analysis, restricted mean survival time and mediation analysis were performed. Appendiceal, pulmonary and early-stage NEN were most commonly diagnosed in females; stomach, pancreatic, small intestinal, colonic, rectal and later-stage NEN were more often diagnosed in males. Females displayed increased survival irrespective of the stage, morphology or level of deprivation. On average, they survived 3.62 (95% CI 1.73-5.90) to 10.26 (6.6-14.45) months longer than males; this was statistically significant in NEN of the lung, pancreas, rectum and stomach ( p < 0.001). The stage mediated improved survival in stomach, lung, and pancreatic NEN but not in rectal NEN. The reasons underlying these differences are not yet understood. Overall, females diagnosed with NEN tend to survive longer than males, and the stage at presentation only partially explains this. Future research, as well as prognostication and treatment, should consider sex as an important factor.

Purpose: This study aims to externally validate the Rotterdam Prostate Cancer Risk Calculator (RPCRC)-3/4 and RPCRC-MRI within a Dutch clinical cohort., Methods: Men subjected to prostate biopsies, between 2018 and 2021, due to a clinical suspicion of prostate cancer (PCa) were retrospectively included. The performance of the RPCRC-3/4 and RPCRC-MRI was analyzed in terms of discrimination, calibration and net benefit. In addition, the need for recalibration and adjustment of risk thresholds for referral was investigated. Clinically significant (cs) PCa was defined as Gleason score ≥ 3 + 4., Results: A total of 1575 men were included in the analysis. PCa was diagnosed in 63.2% (996/1575) of men and csPCa in 41.7% (656/1575) of men. Use of the RPCRC-3/4 could have prevented 37.3% (587/1575) of all MRIs within this cohort, thereby missing 18.3% (120/656) of csPCa diagnoses. After recalibration and adjustment of risk thresholds to 20% for PCa and 10% for csPCa, use of the recalibrated RPCRC-3/4 could have prevented 15.1% (238/1575) of all MRIs, resulting in 5.3% (35/656) of csPCa diagnoses being missed. The performance of the RPCRC-MRI was good; use of this risk calculator could have prevented 10.7% (169/1575) of all biopsies, resulting in 1.2% (8/656) of csPCa diagnoses being missed., Conclusion: The RPCRC-3/4 underestimates the probability of having csPCa within this Dutch clinical cohort, resulting in significant numbers of csPCa diagnoses being missed. For optimal performance of a risk calculator in a specific cohort, evaluation of its performance within the population under study is essential., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: There is ongoing discussion whether a multivariable approach including magnetic resonance imaging (MRI) can safely prevent unnecessary protocol-advised repeat biopsy during active surveillance (AS)., Objective: To determine predictors for grade group (GG) reclassification in patients undergoing an MRI-informed prostate biopsy (MRI-Bx) during AS and to evaluate whether a confirmatory biopsy can be omitted in patients diagnosed with upfront MRI., Design, Setting, and Participants: The Prostate cancer Research International: Active Surveillance (PRIAS) study is a multicenter prospective study of patients on AS (www.prias-project.org). We selected all patients undergoing MRI-Bx (targeted ± systematic biopsy) during AS., Outcome Measurements and Statistical Analysis: A time-dependent Cox regression analysis was used to determine the predictors of GG progression/reclassification in patients undergoing MRI-Bx. A sensitivity analysis and a multivariable logistic regression analysis were also performed., Results and Limitations: A total of 1185 patients underwent 1488 MRI-Bx sessions. The time-dependent Cox regression analysis showed that age (per 10 yr, hazard ratio [HR] 0.84 [95% confidence interval {CI} 0.71-0.99]), MRI outcome (Prostate Imaging Reporting and Data System [PIRADS] 3 vs negative HR 2.46 [95% CI 1.56-3.88], PIRADS 4 vs negative HR 3.39 [95% CI 2.28-5.05], and PIRADS 5 vs negative HR 4.95 [95% CI 3.25-7.56]), prostate-specific antigen (PSA) density (per 0.1 ng/ml cm 3 , HR 1.20 [95% CI 1.12-1.30]), and percentage positive cores on the last systematic biopsy (per 10%, HR 1.16 [95% CI 1.10-1.23]) were significant predictors of GG reclassification. Of the patients with negative MRI and a PSA density of <0.15 ng/ml cm 3 (n = 315), 3% were reclassified to GG ≥2 and 0.6% to GG ≥3. At the confirmatory biopsy, reclassification to GG ≥2 and ≥3 was observed in 23% and 7% of the patients diagnosed without upfront MRI and in 19% and 6% of the patients diagnosed with upfront MRI, respectively. The multivariable analysis showed no significant difference in upgrading at the confirmatory biopsy between patients diagnosed with or without upfront MRI., Conclusions: Age, MRI outcome, PSA density, and percentage positive cores are significant predictors of reclassification at an MRI-informed biopsy. Patients with negative MRI and a PSA density of <0.15 ng/ml cm 3 can safely omit a protocol-based prostate biopsy, whereas in other patients, a multivariable approach is advised. Being diagnosed with upfront MRI appears not to significantly affect reclassification risk; hence, a confirmatory MRI-Bx cannot totally be omitted yet., Patient Summary: A protocol-based prostate biopsy while on active surveillance can be omitted in patients with negative magnetic resonance imaging (MRI) and prostate-specific antigen density <0.15 ng/ml cm 3 . A confirmatory biopsy cannot simply be omitted in all patients diagnosed with upfront MRI., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Castration-resistant prostate cancer (CRPC) remains an incurable and lethal malignancy. The development of new CRPC treatment strategies is strongly impeded by the scarcity of representative, scalable and transferable preclinical models of advanced, androgen receptor (AR)-driven CRPC. Here, we present contemporary patient-derived xenografts (PDXs) and matching PDX-derived organoids (PDXOs) from CRPC patients who had undergone multiple lines of treatment. These models were comprehensively profiled at the morphologic, genomic ( n = 8) and transcriptomic levels ( n = 81). All are high-grade adenocarcinomas that exhibit copy number alterations and transcriptomic features representative of CRPC patient cohorts. We identified losses of PTEN and RB1 , MYC amplifications, as well as genomic alterations in TP53 and in members of clinically actionable pathways such as AR, PI3K and DNA repair pathways. Importantly, the clinically observed continued reliance of CRPC tumors on AR signaling is preserved across the entire set of models, with AR amplification identified in four PDXs. We demonstrate that PDXs and PDXOs faithfully reflect donor tumors and mimic matching patient drug responses. In particular, our models predicted patient responses to subsequent treatments and captured sensitivities to previously received therapies. Collectively, these PDX-PDXO pairs constitute a reliable new resource for in-depth studies of treatment-induced, AR-driven resistance mechanisms. Moreover, PDXOs can be leveraged for large-scale tumor-specific drug response profiling critical for accelerating therapeutic advances in CRPC.