European urology oncology最新文献

{"title":"Gemcitabine-Cisplatin Chemotherapy Induces Nectin-4 Downregulation and Enfortumab Vedotin Resistance in Bladder Cancer.","authors":"Christoph Nössing, Isabella Prantl, Reinhard Grausenburger, Iris E Ertl, Ursula Lemberger, Paula Herek, Luis Rupp, Agata Suleja, Oliver Baumfried, Jule Schrimpf, Christine Pirker, Anna Koren, Stefan Kubicek, Eva Compérat, Markus Eckstein, Walter Berger, Shahrokh F Shariat, Bernhard Englinger","doi":"10.1016/j.euo.2026.08.003","DOIUrl":"https://doi.org/10.1016/j.euo.2026.08.003","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs), particularly enfortumab vedotin (EV) in combination with pembrolizumab, have emerged as transformative treatments for advanced bladder cancer (BC). However, platinum-based chemotherapy, especially gemcitabine-cisplatin (GC), remains a widely used, first-line standard globally. This study investigated the impact of GC-therapy on subsequent ADC responsiveness. Using novel, patient-derived BC models, in vitro selection for acquired GC-resistance consistently resulted in downregulation of the EV target, Nectin-4, and corresponding EV cross-resistance in GC-resistant (GC/R) cells. This decrease in membranous Nectin-4 expression was validated in two independent human BC cohorts: (1) matched transurethral resections and radical cystectomy/lymph node specimens during neoadjuvant therapy and (2) primary tumors and distant metastases during adjuvant GC chemotherapy. Transcriptomic profiling indicated that GC-resistance and Nectin-4 downregulation were linked to a transcriptional shift toward an epithelial-to-mesenchymal transition (EMT)-like phenotype. Large-scale drug screening and transcriptomic data highlighted potential vulnerabilities in GC/R cells, notably associated with the transforming growth factor beta (TGF-beta) signaling pathway. These findings suggest that platinum-based chemotherapy may promote EMT-like transcriptional reprogramming in BC, associated with Nectin-4 loss and EV resistance. As such, assessing membranous Nectin-4 expression prior to EV therapy might be particularly relevant in postplatinum settings. Additionally, identifying alternative, chemotherapy-induced druggable vulnerabilities can inform more effective treatment strategies.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911294","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}

{"title":"Transdermal Estradiol for Treating Prostate Cancer: Revisiting Huggins and Hodges' Revolutionary Breakthrough.","authors":"David J Benjamin, Arash Rezazadeh Kalebasty","doi":"10.1016/j.euo.2026.08.011","DOIUrl":"https://doi.org/10.1016/j.euo.2026.08.011","url":null,"abstract":"<p><p>Androgen deprivation therapy remains the cornerstone of treating prostate cancer and is now available in multiple formulations based on several randomized phase 3 trials. The estradiol patch offers numerous potential advantages, including fewer hot flashes, less adverse impact on bone health, and less financial toxicity.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905618","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}

{"title":"Reply to Francesco Di Bello, Andrea Gallioli, Joan Palou, and Alberto Breda's Letter to the Editor re: Roberto Contieri, Marco Paciotti, Alessandro Uleri et al. Second Transurethral Resection of Bladder Tumor Can Be Safely Omitted in Selected Patients with T1 Non-muscle-invasive Bladder Cancer: Results from the Prospective HuNIRe Trial. Eur Urol Oncol 2026;9:404-12.","authors":"Roberto Contieri, Rodolfo Hurle","doi":"10.1016/j.euo.2026.08.010","DOIUrl":"10.1016/j.euo.2026.08.010","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891513","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}

{"title":"Long-term Prediction of Metastatic Recurrence in Patients Candidate to Radical Prostatectomy Using MRI and Targeted Biopsy: Insights into Tumor Zonal Origin.","authors":"Luc Delobel, Arnauld Villers, Denis Seguier, Philippe Puech, Xavier Leroy, Emeline Cailliau, Jonathan Olivier","doi":"10.1016/j.euo.2026.08.009","DOIUrl":"https://doi.org/10.1016/j.euo.2026.08.009","url":null,"abstract":"<p><p>Prostate cancer recurrence after radical prostatectomy (RP) is primarily driven by tumor aggressiveness, but accurate long-term prediction remains challenging. We evaluated long-term oncological outcomes using magnetic resonance imaging (MRI) and targeted biopsy data in 646 patients treated with RP between 2009 and 2018, and the median follow-up for survivors was 8.3 yr. The primary end point was metastatic recurrence and the secondary end point was biochemical recurrence (BCR). Preoperative variables included MRI-derived tumor volume and quantification of Gleason pattern 4/5 (GP4/5). Tumors were classified according to zonal origin as peripheral zone (PZ) or transition zone/anterior fibromuscular stroma (TZ/AFMS). At 10 yr, metastatic recurrence occurred in 11% (95% confidence interval [CI] = 9-15), including distant metastases in 7.3% (95% CI = 5.1-10). BCR occurred in 28% (95% CI = 24-32). MRI- and biopsy-derived GP4/5 burden strongly predicted metastatic recurrence (c-index 0.82, 95% CI = 0.76-0.88) and BCR (c-index 0.73, 95% CI = 0.69-0.78). Outcomes were consistently worse for PZ compared with TZ tumors, with higher 10-yr BCR rates (32% vs 14%, p = 0.004) and numerically higher metastatic recurrence (8.2% vs 3.7%), with overlapping CIs. These findings provide long-term validation of MRI-based quantification of tumor aggressiveness to predict metastatic recurrence after RP. Although PZ tumors showed consistently worse outcomes in unadjusted analyses, zonal origin was not an independent predictor after multivariable adjustment, suggesting mediation through higher GP4/5 burden.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879271","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}

{"title":"Landscape of Actionable Genetic Alterations in Advanced Urothelial Carcinoma: High Prevalence but Limited Clinical Use.","authors":"Maria Giulia Carta, Lars Tögel, Miriam Angeloni, Marie Sieger, Christian Fiebig, Sven Wach, Helge Taubert, Andreas Manseck, Patrick Adam, Norbert Meidenbauer, Silvia Spoerl, Arndt Hartmann, Bernd Wullich, Florian Haller, Markus Eckstein, Fulvia Ferrazzi","doi":"10.1016/j.euo.2026.07.001","DOIUrl":"https://doi.org/10.1016/j.euo.2026.07.001","url":null,"abstract":"<p><strong>Background and objective: </strong>The Food and Drug Administration and the European Medicine Agency approved erdafitinib for patients with FGFR3-altered metastatic urothelial carcinoma (mUC), highlighting the central role of tumor molecular profiling for patients with mUC. Although different studies described the molecular landscape of muscle-invasive bladder cancer (MIBC) using publicly-available data, a dedicated evaluation of real-world actionable alterations, with evidence-based therapeutic recommendations according to current Molecular Tumor Board (MTB) guidelines, is still lacking.</p><p><strong>Design, setting, and participants: </strong>We characterized actionable genetic alterations in a retrospective cohort of 233 patients with MIBC/mUC (Muscle-Invasive Erlangen [MIER] cohort) using targeted sequencing.</p><p><strong>Outcome measurements and statistical analysis: </strong>Clinically relevant variants were assessed through a custom bioinformatics workflow and expert medical review. To validate their clinical relevance in a real-world setting, we examined actionable alterations and associated therapy recommendations in a cohort of 40 patients with MIBC/mUC undergoing routine diagnostics (MTB cohort).</p><p><strong>Results and limitations: </strong>In the MIER cohort, 95% of patients (n = 226/233; 95% confidence interval [CI], 94-99) harbored at least one pathogenic/likely pathogenic variant. Therapeutically relevant FGFR3 alterations were identified in 11% of patients (n = 26/233; 95% CI, 7.4-16). Additionally, 40% of patients (95% CI, 34-47) showed alterations in 24 biomarkers for FDA-approved therapies. In the MTB cohort, 55% of patients received either on-label (5.0%) or off-label (50%) therapy recommendations. Notably, the recommendation was implemented in only one patient, who achieved stable disease for 4 mo with off-label alpelisib. Retrospectively, similar on-label and off-label indications could have applied to 10% and 70% of patients in the MIER cohort, respectively.</p><p><strong>Conclusions: </strong>Overall, evidence-based indications for on-label and off-label therapies were observed for the majority of patients with MIBC/mUC. However, our results also revealed a significant gap between the high prevalence of actionable findings and the actual implementation of MTB-guided treatments in clinical practice, suggesting a need for enhanced therapy access and physician adherence to MTB recommendations.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864449","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}

{"title":"Alkaline Phosphatase and Prostate-specific Antigen Response in Metastatic Castration-resistant Prostate Cancer Treated with Enzalutamide Alone or in Combination with Radium-223: Ad Hoc Analysis of the PEACE-3 Consortium Trial.","authors":"Andrey Soares, Silke Gillessen, Ananya Choudhury, Fred Saad, Enrique Gallardo, Yohann Loriot, Raymond S McDermott, Alejo Rodriguez-Vida, Pedro Isaacsson Velho, Franco Nolè, Felipe Melo Cruz, Thierry André Roumeguère, Gedske Daugaard, Rosely Yamamura, Coralie Poncet, Corneel Coens, Béatrice Fournier, Bertrand F Tombal","doi":"10.1016/j.euo.2026.08.001","DOIUrl":"https://doi.org/10.1016/j.euo.2026.08.001","url":null,"abstract":"<p><strong>Design, setting, and participants: </strong>Exploratory post hoc analysis of the international, randomised, open-label phase 3 PEACE-3 trial including 446 patients with asymptomatic or mildly symptomatic mCRPC and bone metastases. Overall, 441 and 436 patients were evaluable for ALP and PSA, respectively.</p><p><strong>Intervention: </strong>Enzalutamide 160 mg daily alone or combined with six-monthly injections of radium-223 (55 kBq/kg).</p><p><strong>Outcome measurements and statistical analysis: </strong>ALP response was defined as a ≥30% decline from baseline (ALP-30), and PSA response as a≥50% decline (PSA-50) or ≥90% decline (PSA-90). Confirmed responses required consecutive measurements ≥21 d apart. Time-to-event endpoints were analysed using Kaplan-Meier and Cox models.</p><p><strong>Results and limitations: </strong>At 6 months, confirmed ALP-30 response was 56.5% with the combination versus 50.8% with enzalutamide alone. Median time to confirmed ALP-30 response was 2.4 versus 3.7 months (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.12-1.78; p = 0.003), and time to ALP normalisation was 2.0 versus 4.5 months (HR 2.05, 95% CI 1.46-2.88; p < 0.001). Confirmed PSA-90 response at 6 months was 50.5% versus 34.1% (p = 0.001), with median time to confirmed PSA-90 response of 5.6 versus 22.1 months (HR 1.48, 95% CI 1.13-1.93; p = 0.004). Limitations include the exploratory post hoc design, the absence of multiplicity adjustment, and the lack of an analysis linking biomarker responses to clinical outcomes.</p><p><strong>Conclusions: </strong>Adding radium-223 to enzalutamide was associated with faster and more frequent ALP and deep PSA responses. These findings support additional antitumour activity of radium-223 when combined with enzalutamide.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849932","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}

{"title":"Rethinking EZH2 Inhibition: A Priming Strategy for EGFR-targeted Therapy in Bladder Cancer.","authors":"Christoph Nössing, Iris E Ertl, Bernhard Englinger","doi":"10.1016/j.euo.2026.08.006","DOIUrl":"https://doi.org/10.1016/j.euo.2026.08.006","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817367","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}

{"title":"Re: Contieri R, Paciotti M, Uleri A, et al. Patients with T1 Non-muscle-invasive Bladder Cancer: Results from the Prospective HuNIRe Trial. Eur Urol Oncol. 2026;9:404-412.","authors":"Roberto Mario Scarpa","doi":"10.1016/j.euo.2026.07.020","DOIUrl":"https://doi.org/10.1016/j.euo.2026.07.020","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790419","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}

{"title":"Re: Roberto Contieri, Marco Paciotti, Alessandro Uleri, et al. Second Transurethral Resection of Bladder Tumor Can Be Safely Omitted in Selected Patients with T1 Non-muscle-invasive Bladder Cancer: Results from the Prospective HuNIRe Trial. Eur Urol Oncol 2026;9:404-12.","authors":"Francesco Di Bello, Andrea Gallioli, Joan Palou, Alberto Breda","doi":"10.1016/j.euo.2026.07.021","DOIUrl":"https://doi.org/10.1016/j.euo.2026.07.021","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790424","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}

{"title":"Incidence of Germline Genetic Variants in Patients with a Urinary Tract Cancer and Association with Outcomes.","authors":"Kent Kamau, Lindsey Byrne, Rajvi Goradia, Debasish Sundi, Lingbin Meng, Yuanquan Yang, Timothy D Gauntner, Shang-Jui Wang, Steven K Clinton, Amir Mortazavi, Daniel G Stover, Akshay Sood, Katharine A Collier","doi":"10.1016/j.euo.2026.07.017","DOIUrl":"10.1016/j.euo.2026.07.017","url":null,"abstract":"<p><strong>Background and objective: </strong>Lynch syndrome (LS) and germline DNA damage repair (DDR) mutations have been described in urothelial carcinoma (UC). However, the incidence in unselected cohorts and the impact on outcomes remain unclear.</p><p><strong>Design: </strong>We performed a retrospective study to determine the frequency of pathogenic/likely pathogenic (P/LP) germline variants in 78 known cancer predisposition genes among 273 patients with urinary tract cancer (UTC) of the bladder, renal pelvis, ureter, and/or urethra and validated the frequency in an independent cohort of 5972 patients. We identified variants in germline whole-exome sequencing that were overrepresented in UTC. We measured associations with treatment-related outcomes.</p><p><strong>Results and limitations: </strong>In unselected cohorts, 9.3-9.5% of the patients with UTC harbored a variant in a cancer predisposition gene. No clinicodemographic variable predicted the presence of a P/LP variant. LS was found in 0.7-0.8% of the patients who were more likely to have upper tract disease and strong personal and family histories of malignancy. Non-Lynch DDR variants occurred in 6.6-8.0% of the patients, most often in CHEK2, BRCA1, BRCA2, and ATM. Very small cohorts of patients with UC and LS or a DDR variant responded well to immune checkpoint inhibitors (ICIs) or platinum chemotherapy, respectively. Standard variant calling methods may miss large deletions.</p><p><strong>Conclusions: </strong>The incidence of P/LP germline variants in UTC is clinically meaningful, and more than one-third of the patients are missed with current guidelines. The response of UC with LS to ICI and with DDR to platinum is hypothesis generating and warrants further investigation.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}