European urologyPub Date : 2025-07-01DOI: 10.1016/j.eururo.2025.06.015
Susan Halabi, Siyuan Guo
{"title":"How To Interpret Subgroup Analyses from Prospective Randomized Clinical Trials: What Clinicians Need To Know","authors":"Susan Halabi, Siyuan Guo","doi":"10.1016/j.eururo.2025.06.015","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.06.015","url":null,"abstract":"<h2>Section snippets</h2><section><section><section><h2>Inflated type I errors</h2>Most RCTs are designed to test the overall treatment effect and not for detection of effects in subgroups. With each additional subgroup comparison, the likelihood of a false-positive result increases. For example, testing five independent subgroups yields a 23% chance of observing at least one <em>p</em> value <0.05 by chance alone, which rises to 40% with ten independent subgroups (Fig. 1A). Moreover, the probability of seeing a reversal of a treatment effect in at least one subgroup is surprisingly</section></section></section><section><section><h2>Levels of evidence and the role of meta-analysis</h2>The credibility of a subgroup claim depends on the study design and context. Prespecified analyses with adequate power, significant interaction tests, and a biological rationale carry more weight than post hoc findings (Fig. 2A). In the CHAARTED trial, a prespecified subgroup analysis showed that men with high-disease volume metastatic hormone-sensitive prostate cancer (mHSPC) had longer OS with androgen deprivation therapy (ADT) + docetaxel than with ADT alone (hazard ratio 0.60, 95%</section></section><section><section><h2>Traditional versus data-driven subgroup definitions</h2>Subgroup definitions have traditionally relied on clinical judgment and biological rationale, such as classification of patients by tumor stage, biomarker expression, or prior treatments. These categories are grounded in existing knowledge and are easier to interpret and communicate. However, they may overlook more complex predictors of treatment heterogeneity.By contrast, data-driven methods such as recursive partitioning, clustering, and machine-learning algorithms can uncover unrecognized</section></section><section><section><h2>Conclusions</h2>Subgroup analyses must be approached with caution. Unless such analyses are prespecified at the design stage, any findings should be considered exploratory and confirmed in future trials (Fig. 2B). Poorly designed subgroup analyses risk misleading interpretation and may erode trust among clinicians, regulators, and the public. Credible subgroup claims require safeguards such as prespecification, adequate power, formal interaction testing, and meta-analysis. Statistical reporting should</section></section>","PeriodicalId":12223,"journal":{"name":"European urology","volume":"33 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
European urologyPub Date : 2025-07-01DOI: 10.1016/j.eururo.2025.05.039
Jonathan F. Anker, Menggang Yu, Matthew D. Galsky
{"title":"Association Between Circulating Tumor DNA and Clinical Outcomes with Adjuvant Immune Checkpoint Blockade in Patients with Muscle-invasive Bladder Cancer Treated with Neoadjuvant Chemotherapy Followed by Cystectomy","authors":"Jonathan F. Anker, Menggang Yu, Matthew D. Galsky","doi":"10.1016/j.eururo.2025.05.039","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.05.039","url":null,"abstract":"No Abstract","PeriodicalId":12223,"journal":{"name":"European urology","volume":"19 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
European urologyPub Date : 2025-07-01DOI: 10.1016/j.eururo.2025.06.014
Marco Paciotti, Andrea Piccolini, Alessandro Uleri, Stefano Moretto, Vittorio Fasulo, Massimo Lazzeri, Giovanni Lughezzani, Paolo Casale, Nicolò Maria Buffi
{"title":"Robotic Surgery and Patient Safety: A Global Assessment of Technological Malfunctions During da Vinci X and Xi Procedures","authors":"Marco Paciotti, Andrea Piccolini, Alessandro Uleri, Stefano Moretto, Vittorio Fasulo, Massimo Lazzeri, Giovanni Lughezzani, Paolo Casale, Nicolò Maria Buffi","doi":"10.1016/j.eururo.2025.06.014","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.06.014","url":null,"abstract":"No Abstract","PeriodicalId":12223,"journal":{"name":"European urology","volume":"152 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
European urologyPub Date : 2025-06-26DOI: 10.1016/j.eururo.2025.05.013
Sarah Burdett, David J. Fisher, Jayne F. Tierney, Adrian D. Cook, Daniel E. Spratt, James J. Dignam, Wendy F. Seiferheld, Amar U. Kishan, Yilun Sun, Sylvie Chabaud, Jason A. Efstathiou, Christopher C. Parker, Alan Pollack, Paul Sargos, Igor Latorzeff, Meryem Brihoum, Charles N. Catton, Noel W. Clarke, Felix Y. Feng, Theodore G. Karrison, Claire L. Vale
{"title":"Duration of Androgen Suppression with Postoperative Radiotherapy (DADSPORT) for Nonmetastatic Prostate Cancer: A Collaborative Systematic Review and Meta-analysis of Aggregate Data","authors":"Sarah Burdett, David J. Fisher, Jayne F. Tierney, Adrian D. Cook, Daniel E. Spratt, James J. Dignam, Wendy F. Seiferheld, Amar U. Kishan, Yilun Sun, Sylvie Chabaud, Jason A. Efstathiou, Christopher C. Parker, Alan Pollack, Paul Sargos, Igor Latorzeff, Meryem Brihoum, Charles N. Catton, Noel W. Clarke, Felix Y. Feng, Theodore G. Karrison, Claire L. Vale","doi":"10.1016/j.eururo.2025.05.013","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.05.013","url":null,"abstract":"<h3>Background and objective</h3>To better understand the role of hormone therapy (HT) with postoperative radiotherapy (RT) for nonmetastatic prostate cancer, the DADSPORT Collaboration planned a systematic review and meta-analysis of aggregate data from randomised controlled trials (RCTs).<h3>Methods</h3>RCTs evaluating HT with postoperative RT in people with nonmetastatic prostate cancer were identified. Methods were prespecified prior to results of recent trials being known (CRD42022325769). The primary outcome was overall survival (OS); metastasis-free survival (MFS) and prostate cancer–specific survival (PCSS) were the secondary outcomes. Summary results, including those by prespecified participant subgroups, were obtained from investigators and combined across trials using a fixed-effect meta-analysis. Sensitivity and network meta-analyses evaluated the consistency of findings.<h3>Key findings and limitations</h3>Five RCTs (six trial comparisons, 4411 participants; 96% of all eligible) were included in the primary analysis. There was no clear evidence that OS was improved with HT (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.74–1.00, <em>p</em> = 0.057; absolute effect 2% [0–3.5%] at 8 yr) or that effects varied by HT duration (<em>p</em> = 0.6). Any benefit of HT on OS appears to be confined to people with higher pre-RT prostate specific antigen levels (<em>p</em> = 0.07) and CAPRA-S scores (<em>p</em> = 0.09). HT significantly improved MFS (HR = 0.78, 95% CI = 0.69–0.88, <em>p</em> < 0.001) and PCSS (HR = 0.61, 95% CI = 0.47–0.79, <em>p</em> < 0.001), with 4% absolute improvements for both outcomes at 8 yr.<h3>Conclusion and clinical implications</h3>Short- or long-course HT after postoperative RT improves MFS and PCSS. Observed improvements in OS are small and may be limited to people with higher-risk factors.","PeriodicalId":12223,"journal":{"name":"European urology","volume":"139 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
European urologyPub Date : 2025-06-25DOI: 10.1016/j.eururo.2025.06.011
Sigrid V. Carlsson
{"title":"Rethinking Early Detection: Magnetic Resonance Imaging Strategies for Smarter Prostate Cancer Screening","authors":"Sigrid V. Carlsson","doi":"10.1016/j.eururo.2025.06.011","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.06.011","url":null,"abstract":"No Abstract","PeriodicalId":12223,"journal":{"name":"European urology","volume":"12 2 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
European urologyPub Date : 2025-06-25DOI: 10.1016/j.eururo.2025.06.012
Emmeli Palmstedt, Marianne Månsson, Jonas Hugosson, Rebecka Arnsrud Godtman
{"title":"Active Surveillance for Screen-detected Low- and Intermediate-risk Prostate Cancer: Extended Follow-up up to 25 Years in the GÖTEBORG-1 Trial","authors":"Emmeli Palmstedt, Marianne Månsson, Jonas Hugosson, Rebecka Arnsrud Godtman","doi":"10.1016/j.eururo.2025.06.012","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.06.012","url":null,"abstract":"<h3>Background and objective</h3>Active surveillance (AS) is used to postpone or avoid surgery or radiotherapy for prostate cancer (PC). While the risk of PC-related death remains low for patients deferring treatment, follow-up data have previously been limited to 15 yr. Since many men outlive this timeframe, studying long-term outcomes is crucial.<h3>Methods</h3>We included 488 men with screen-detected PC in the GÖTEBORG-1 screening trial managed with AS, of whom 251 were at a very low risk, 129 at a low risk, and 108 at an intermediate risk. Prostate-specific antigen (PSA) testing was performed every 6–12 mo, and repeated biopsies were indicated if there were signs of clinical progression. Treatment was recommended upon progression (PSA, grade, or stage). Kaplan-Meier analyses were performed for treatment-free, failure-free, and PC-specific survival, measuring time from diagnosis to an event or the last follow-up.<h3>Key findings and limitations</h3>During a median follow-up of 18 yr, a total of 232 men discontinued AS, 81 experienced failure, and 14 died from PC. The treatment-free survival rate at 22 yr was 38% for the entire cohort . At 19 yr, treatment-free survival rates were 55% for very-low-risk, 35% for low-risk, and 30% for intermediate-risk PC. The failure-free survival rate at 22 yr for all men was 68%, and at 19 yr, the rates were 85% for very-low-risk, 74% for low-risk, and 55% for intermediate-risk cases. The PC-specific survival rate at 25 yr for the entire cohort was 94%. At 24 yr, these rates were 99% for very-low-risk, 92% for low-risk, and 85% for intermediate-risk PC. The overall survival rate at 25 yr for all men was 32%, and at 24 yr, the rates were 38% for very-low-risk, 34% for low-risk, and 22% for intermediate-risk PC. The limitation was no predefined AS protocol.<h3>Conclusions and clinical implications</h3>This study confirms a low risk of PC death with a median follow-up of 18 yr. The risk of failure increased over time, highlighting the need for life-long monitoring. Providing men information about this risk is important.","PeriodicalId":12223,"journal":{"name":"European urology","volume":"148 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
European urologyPub Date : 2025-06-24DOI: 10.1016/j.eururo.2025.05.040
Thomas Dreyer, Jørgen Bjerggaard Jensen
{"title":"Reply to Xin Rui, Xiaoming Xu, and Bo Dai’s Letter to the Editor re: Thomas Dreyer, Simone Brandt, Knud Fabrin, et al. Use of the Xpert Bladder Cancer Monitor Urinary Biomarker Test for Guiding Cystoscopy in High-grade Non–muscle-invasive Bladder Cancer: Results from the Randomized Controlled DaBlaCa-15 Trial. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2025.03.018","authors":"Thomas Dreyer, Jørgen Bjerggaard Jensen","doi":"10.1016/j.eururo.2025.05.040","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.05.040","url":null,"abstract":"No Abstract","PeriodicalId":12223,"journal":{"name":"European urology","volume":"16 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144371026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
European urologyPub Date : 2025-06-23DOI: 10.1016/j.eururo.2025.06.006
Madeleine J. Karpinski, Boris A. Hadaschik, Wolfgang P. Fendler
{"title":"Reply to Zhengbo Pan, Run Shi, and Zhaokai Zhou’s Letter to the Editor - Re: Madeleine J. Karpinski, Kambiz Rahbar, Martin Bögemann, et al. Updated Prostate Cancer Risk Groups by Prostate-specific Membrane Antigen Positron Emission Tomography Prostate Cancer Molecular Imaging Standardized Evaluation (PPP2): Results from an International Multicentre Registry Study. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2025.04.017","authors":"Madeleine J. Karpinski, Boris A. Hadaschik, Wolfgang P. Fendler","doi":"10.1016/j.eururo.2025.06.006","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.06.006","url":null,"abstract":"No Abstract","PeriodicalId":12223,"journal":{"name":"European urology","volume":"143 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
European urologyPub Date : 2025-06-21DOI: 10.1016/j.eururo.2025.06.009
Ian D. Davis
{"title":"If the Treatment for Metastatic Hormone-sensitive Prostate Cancer Stops Working, What Next?","authors":"Ian D. Davis","doi":"10.1016/j.eururo.2025.06.009","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.06.009","url":null,"abstract":"No Abstract","PeriodicalId":12223,"journal":{"name":"European urology","volume":"5 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}