European urology oncology最新文献

{"title":"Molecular Profiling of Urothelial Bladder Cancer: Bridging Tumor Biology and Clinical Decision-making","authors":"Constance Thibault, Hélène Blons, Yves Allory, Alia Harba, Mathieu Roumiguié, Thomas Seisen, Gautier Marcq, Anne Sophie Bajeot, Priscilla Leon, Alexandra Masson-Lecomte, Benjamin Pradère, Evanguelos Xylinas, Doriane Prost, Pierre-Etienne Gabriel, Pierre Laurent-Puig, Morgan Rouprêt, Francois Audenet, for the Cancer Committee of The French Association of Urology (CC-AFU)","doi":"10.1016/j.euo.2026.06.012","DOIUrl":"10.1016/j.euo.2026.06.012","url":null,"abstract":"<div><h3>Context</h3><div>Bladder cancer ranks among the most common malignancies worldwide, with urothelial carcinoma as the predominant histological type. Its development from normal urothelium to non–muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC) is driven by complex molecular events, including chromosomal aberrations, somatic mutations, and epigenetic dysregulation. Advances in next-generation sequencing (NGS) and transcriptomic profiling have transformed the understanding of urothelial tumor biology and opened new perspectives for precision oncology.</div></div><div><h3>Objective</h3><div>To provide an updated synthesis of molecular profiling in urothelial bladder cancer across disease stages and to discuss its diagnostic, prognostic, and therapeutic relevance.</div></div><div><h3>Evidence acquisition</h3><div>We conducted a targeted narrative review based on a structured PubMed search of studies published between January 2000 and February 2026 using the keywords “genomic,” “epigenetic,” “transcriptomic,” and “urothelial bladder cancer.” Eligible publications included original research articles, reviews, and meta-analyses in English. Evidence was synthesized across NMIBC, MIBC, and metastatic disease, focusing on molecular alterations and their clinical relevance.</div></div><div><h3>Evidence synthesis</h3><div>Both NMIBC and MIBC present frequent <em>TERT</em> promoter mutations. NMIBC is further characterized by frequent <em>FGFR3</em> and <em>PIK3CA</em> mutations, loss of chromosome 9, and widespread chromatin-remodeling gene alterations. MIBC displays high genomic instability, with recurrent mutations in <em>TP53</em>, <em>RB1</em>, and chromatin modifiers, as well as frequent alterations in the RTK/RAS/PI3K pathway. Consensus transcriptomic classifications identify reproducible molecular subtypes (luminal, basal/squamous, stroma rich, and neuroendocrine like), each with distinct biological and clinical behaviors. In metastatic disease, NGS and whole-exome analyses reveal strong concordance with localized tumors, with frequent <em>TP53</em>, <em>ARID1A</em>, <em>KMT2D</em>, <em>RB1</em>, and <em>FGFR3</em> alterations and APOBEC mutational signatures. Transcriptomic profiling shows subtype heterogeneity and therapy-induced remodeling. Clinically, only <em>FGFR3</em> alterations currently guide therapy, with erdafitinib approved by the US Food and Drug Administration and the European Medicines Agency for <em>FGFR3</em>-altered metastatic disease. Beyond tumor testing, circulating tumor DNA assays show promise for molecular residual disease detection and adjuvant treatment stratification.</div></div><div><h3>Conclusions</h3><div>Molecular profiling has deepened the understanding of bladder cancer biology and identified potential biomarkers for diagnosis, prognosis, and treatment. However, clinical implementation remains limited, and prospective biomarker-driven trials are needed to establish the role of ge","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 986-996"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410739","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}

{"title":"Re: Martino Pedrani, Alberto De Giorgi, Andrea Gallina, et al. When Patients Refuse Radical Cystectomy: Integrating Trimodality Therapy in the Perioperative ICI/ADC Era. Eur Urol Oncol. 2026;9:743–745. http://dx.doi.org/10.1016/j.euo.2026.04.008","authors":"Kelly M. de Ligt, Sarah P. Psutka, Laura S. Mertens","doi":"10.1016/j.euo.2026.06.016","DOIUrl":"10.1016/j.euo.2026.06.016","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 1021-1022"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419930","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 Cameron E. Alexander, Ashwin Sachdeva, and Noel W. Clarke’s Letter to Editor Re: Develtere D, Devos G. Metformin in prostate cancer: A negative repurposing story across the disease continuum. Urol Oncol 2026. https://doi.org/10.1016/j.euo.2026.04.014.","authors":"Dries Develtere, Gaëtan Devos","doi":"10.1016/j.euo.2026.06.015","DOIUrl":"10.1016/j.euo.2026.06.015","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Page 1020"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419957","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":"Validation of an AI-based Histologic Prognostic Biomarker in Patients with Non–muscle-invasive Bladder Cancer Using the Prospective Swedish National Register of Urinary Bladder Cancer","authors":"Per-Uno Malmström, Anca Dragomir, Truls Gårdmark","doi":"10.1016/j.euo.2026.07.002","DOIUrl":"10.1016/j.euo.2026.07.002","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 1010-1011"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668867","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":"A Long Noncoding RNA–based Classifier for Identifying More Aggressive Low-grade Ta Bladder Cancer with Elevated FGFR3 Activity","authors":"Tran Anh Thu Phung,&nbsp;Rachel Weng,&nbsp;Peter C. Black,&nbsp;Lars Dyrskjøt,&nbsp;Joep J. de Jong,&nbsp;Ewan A. Gibb","doi":"10.1016/j.euo.2026.02.020","DOIUrl":"10.1016/j.euo.2026.02.020","url":null,"abstract":"<div><h3>Background and objective</h3><div>Low-grade, stage Ta (TaLG) non–muscle-invasive bladder cancer (NMIBC) is generally nonaggressive; yet, some patients experience recurrence or progression. We previously identified long noncoding RNA cluster 2 (LC2) as an aggressive TaLG subgroup via consensus clustering, which required a cohort-level analysis. We developed a single-sample transcriptome classifier for patient-level LC2 identification.</div></div><div><h3>Methods</h3><div>Using the UROMOL cohort (<em>n</em> = 276) for training/testing and the Hurst (Stage-stratified molecular profiling of non-muscle-invasive bladder cancer enhances biological, clinical, and therapeutic insight. Cell Rep Med 2021;2:100472) cohort (<em>n</em> = 72) for validation, we performed feature selection via median absolute deviation and nested cross-validation. An elastic net regression model (<em>α</em> = 0.5) was trained using ten-fold cross-validation. Performance was evaluated through a pathway analysis, with prognostic significance assessed by Kaplan-Meier and univariable Cox regression.</div></div><div><h3>Key findings and limitations</h3><div>Biological characterization revealed that LC2 tumors exhibited higher proliferation (G2M/E2F signatures), elevated FGFR3 pathway activity, and reduced sonic hedgehog signaling and immune activity (<em>p</em> &lt; 0.001). The classifier identified 7/72 LC2 tumors in the Hurst cohort. LC2-TaLG patients had significantly worse recurrence-free survival (log-rank <em>p</em> &lt; 0.001). On univariable Cox regression analysis, LC2 status was strongly associated with recurrence (hazard ratio 4.52, 95% confidence interval 1.78–11.5; <em>p</em> = 0.001). LC2-predicted tumors in the Hurst cohort showed similar biological patterns.</div></div><div><h3>Conclusions and clinical implications</h3><div>We developed a single-sample transcriptomic classifier identifying aggressive TaLG NMIBC, demonstrating reproducibility across platforms. If validated, this model has the potential to support clinical decision-making.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 814-821"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321524","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}

{"title":"Impact of Intravesical Bacillus Calmette-Guérin Therapy Following Transurethral En Bloc Resection of Bladder Tumour: Post Hoc Analysis of a Randomised, Multicentre, Phase 3 Trial","authors":"Jeremy Yuen-Chun Teoh,&nbsp;Chris Ho-Ming Wong,&nbsp;Cheung-Hing Cheng,&nbsp;Chiu-Fung Tsang,&nbsp;Joseph Kai-Man Li,&nbsp;Bryan Kwun-Chung Cheng,&nbsp;Wilson Hoi-Chak Chan,&nbsp;Wayne Kwun-Wai Chan,&nbsp;Trevor Churk-Fai Li,&nbsp;Yi Chiu,&nbsp;Man-Chung Law,&nbsp;Clarence Lok-Hei Leung,&nbsp;Brian Sze-Ho Ho,&nbsp;Chris Yue-Kit Lee,&nbsp;Ronald Cheong-Kin Chan,&nbsp;Eddie Shu-Yin Chan,&nbsp;Tsz-Yeung Chan,&nbsp;James Hok-Leung Tsu,&nbsp;Ho-Man Tam,&nbsp;Kin-Man Lam,&nbsp;Chi-Fai Ng","doi":"10.1016/j.euo.2025.09.008","DOIUrl":"10.1016/j.euo.2025.09.008","url":null,"abstract":"<div><div>We conducted a post hoc analysis of the EB-StaR study (NCT02993211) to assess the impact of intravesical bacillus Calmette-Guérin (BCG) therapy following en bloc resection of bladder tumour (ERBT) or standard resection (SR) in patients with non–muscle-invasive bladder cancer (NMIBC). The outcome measures were the 1-yr recurrence and progression rates. Among the 276 patients included in the analysis, 1-yr recurrence rates were 33% (95% confidence interval [CI] 21–43%) in the ERBT alone group versus 41% (95% CI 30–50%) in the SR alone group (<em>p</em> = 0.02); and 5% (95% CI 0–14%) in the ERBT + BCG group versus 26% (95% CI 5.8–42%) in the SR + BCG group (<em>p</em> = 0.059). The 1-yr progression rates were 0% in the ERBT alone group versus 2% (95% CI 0–4.6%) in the SR alone group (<em>p</em> = 0.13); and 0% in the ERBT + BCG group versus 5.6% (95% CI 0–16%) in the SR + BCG group (<em>p</em> = 0.4). The combination of ERBT and intravesical BCG therapy appeared to yield excellent oncological control, resulting in a 1-yr recurrence rate of 5% among patients with high-risk NMIBC. Good-quality surgery plus good adjuvant therapy should be considered vital components in optimising long-term oncological outcomes in NMIBC.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 761-765"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430591","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}

{"title":"An Open-label, Phase 1 Dose-finding Study of Single-agent IMU-935, a Novel RORγ/RORγt Inverse Agonist, in Patients with Progressive Metastatic Castration-resistant Prostate Cancer","authors":"Rafael Grochot,&nbsp;Christina Guo,&nbsp;Suzanne Carreira,&nbsp;Mateus Crespo,&nbsp;Jon Welti,&nbsp;Susana Miranda,&nbsp;Ines Figueiredo,&nbsp;Claudia Bertan,&nbsp;Jan Rekowski,&nbsp;Wei Yuan,&nbsp;Nina Tunariu,&nbsp;Katarzyna Abramowicz,&nbsp;Ana Ferreira,&nbsp;Ruth Riisnaes,&nbsp;Antje Neeb,&nbsp;Bora Gurel,&nbsp;Maria de Los Dolores Fenor de la Maza,&nbsp;Khobe Chandran,&nbsp;Juliet Carmichael,&nbsp;Daniel Westaby,&nbsp;Johann de Bono","doi":"10.1016/j.euo.2026.02.014","DOIUrl":"10.1016/j.euo.2026.02.014","url":null,"abstract":"<div><h3>Background and objective</h3><div>Retinoic acid receptor–related orphan receptor gamma (ROR<strong>γ</strong>) is frequently overexpressed in metastatic castration-resistant prostate cancer (mCRPC) and, together with retinoic acid–related orphan receptor gamma t (RORγt), can increase androgen receptor (AR) signalling and promote a proinflammatory tumour microenvironment.</div></div><div><h3>Methods</h3><div>In this phase 1 dose-finding study (NCT05124795), men with mCRPC received the oral RORγ/RORγt inverse agonist IMU-935 across three dose levels (150 mg, 300 mg, or 450 mg twice daily). The primary objective was to determine the recommended phase 2 dose according to a Bayesian optimal interval design. Key secondary endpoints included evaluation of pharmacokinetics and pharmacodynamics, as well as antitumour activity in terms of prostate-specific antigen (PSA), circulating tumour cells (CTCs), and responses according to Response Evaluation Criteria in Solid Tumours.</div></div><div><h3>Key findings and limitations</h3><div>Eighteen men received IMU-935. No dose-limiting toxicities (DLTs) or any grade (G) ≥3 adverse events (AEs) were reported. The most common treatment-related AEs (TRAEs) were G1 nausea (<em>n</em> = 4; 22%) and G1 vomiting (<em>n</em> = 3; 17%). The only G2 TRAEs observed were anaemia (<em>n</em> = 2; 11%) and gastroesophageal reflux disease (<em>n</em> = 1; 6%). Overall, six men (33%) had a decrease in CTC level from ≥5 to &lt;5 cells/7.5 ml, while one participant whose tumour had mismatch repair deficiency (MMRd) experienced a ≥50% decline in PSA and radiologically stable disease for &gt;6 mo. The median time to PSA progression was 8 wk (range 2–36 wk), and median radiological progression-free survival was 11 wk (range 3.4–36 wk).</div></div><div><h3>Conclusions and clinical implications</h3><div>IMU-935 was well tolerated with no DLTs. One participant with MMRd mCRPC experienced a PSA response. Overall, however, robust antitumour activity was not observed in this molecularly unselected cohort.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 804-813"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147443033","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}

{"title":"Prognostic Factors for Overall Survival in the VESPER Trial: Basal Molecular Subtype Is a Relevant Key Factor","authors":"Christian Pfister,&nbsp;Valentin Harter,&nbsp;Jacqueline Fontugne,&nbsp;Yves Allory,&nbsp;Stéphane Culine","doi":"10.1016/j.euo.2026.01.003","DOIUrl":"10.1016/j.euo.2026.01.003","url":null,"abstract":"<div><h3>Background and objective</h3><div>Our aim was to identify potential prognostic factors for overall survival (OS) for patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy (NAC) and cystectomy in the VESPER trial (NCT01812369).</div></div><div><h3>Methods</h3><div>We focused on the NAC VESPER population (<em>n</em> = 437), including 218 patients who received dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin, and 219 who received gemcitabine and cisplatin. Tumor slides and formalin-fixed, paraffin-embedded blocks were available for central review in 297 cases of urothelial carcinoma. We investigated the effect of clinical, biological, pathological, and molecular characteristics on OS.</div></div><div><h3>Key findings and limitations</h3><div>Univariate analysis identified creatinine clearance, lymphovascular invasion, perineural invasion, and molecular subtype as factors with prognostic relevance for OS. Basal/squamous molecular subtype was the only covariate with the entire confidence interval greater than 0.5 for the time-dependent area under the receiver operating characteristic curve at 1, 3, and 5 yr, which suggests high prognostic value. Multivariable analysis demonstrated that these four prognostic factors were complementary for OS prediction. We did not observe a major difference in the 5-yr OS rate between groups with none of these factors (72%, 95% confidence interval [CI] 63–82%) or only one factor (67%, 95% CI 59–76%). By contrast, the 5-yr OS rate was lower for the group with two or more factors (38%, 95% CI 28–53%).</div></div><div><h3>Conclusions and clinical implications</h3><div>We identified four factors prognostic for OS for patients with MIBC treated with NAC in VESPER. Basal molecular subtype was the most significant prognostic factor for OS, as it was independent of the treatment arm, and showed high prognostic value, in particular during the first year after randomization.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 795-803"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040571","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}

{"title":"Health-related Quality of Life Outcomes of Salvage Metastasis-directed Treatment Versus Elective Nodal Treatment for Oligorecurrent Nodal Prostate Cancer: A Secondary Analysis of the Phase 2, Open-label PEACE V–STORM Randomized Trial","authors":"Thomas Zilli,&nbsp;Shankar Siva,&nbsp;Sigmund Brabrand,&nbsp;Piet Dirix,&nbsp;Nick Liefhooghe,&nbsp;François-Xavier Otte,&nbsp;Alfonso Gomez-Iturriaga,&nbsp;Wouter Everaerts,&nbsp;Mohamed Shelan,&nbsp;Antonio Conde-Moreno,&nbsp;Fernando López Campos,&nbsp;Alexandros Papachristofilou,&nbsp;Matthias Guckenberger,&nbsp;Marta Scorsetti,&nbsp;Almudena Zapatero,&nbsp;Ana-Elena Villafranca Iturre,&nbsp;Clara Eito,&nbsp;Felipe Couñago,&nbsp;Paolo Muto,&nbsp;Wim Duthoy,&nbsp;Piet Ost","doi":"10.1016/j.euo.2026.01.001","DOIUrl":"10.1016/j.euo.2026.01.001","url":null,"abstract":"<div><div>For prostate cancer patients with metachronous nodal oligorecurrences detected by positron emission tomography, the randomized phase 2 PEACE V–STORM trial (NCT03569241) demonstrated that, compared with metastasis-directed therapy (MDT), elective nodal pelvic radiotherapy (ENRT) in combination with 6 mo of androgen deprivation therapy (ADT) improved locoregional disease control and metastasis-free survival. In the 190 evaluable patients (MDT: 97 and ENRT: 93) of the 196 randomized in the study, health-related quality of life (HRQoL) was assessed by European Organization for Research and Treatment of Cancer QLQ-C-30 and QLQ-PR-25 questionnaires over a 4-yr period as a part of a statistically defined quality of life analysis. During a median follow-up of 50 mo (interquartile range 42–58), QLQ-C30 scores showed no significant differences between MDT and ENRT, except for worse physical functioning at month 24 in the ENRT group (mean decline −7.7 vs −1.3) and worse emotional functioning at month 12 in the MDT group (mean decline 5.8 vs −0.4, <em>p</em> = 0.034). No significant differences in QLQ-PR25 scores were observed, except slightly better bowel symptoms at 18 mo for ENRT, but with no difference before or after. The decline in sexual activity and increase in ADT-related symptoms during the first 6 mo were comparable between arms, returning to baseline by month 12. Consistent with physician-reported treatment-related adverse events, HRQoL analyses show no significant differences between ENRT and MDT.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 766-771"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017947","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}

{"title":"Individual Patient Data Validation of the EAU Definitions of BCG Failure in Patients with Non–muscle-invasive Urothelial Carcinoma of the Bladder: An International Multicenter Retrospective Study","authors":"P. Gontero,&nbsp;F. Soria,&nbsp;M. Babjuk,&nbsp;M. Burger,&nbsp;J. Palou Redorta,&nbsp;D. D’Andrea,&nbsp;B. Pradere,&nbsp;M. Moschini,&nbsp;A. Birtle,&nbsp;E.M. Compérat,&nbsp;J.L. Dominguez-Escrig,&nbsp;F. Liedberg,&nbsp;P. Mariappan,&nbsp;B.W.G. van Rhijn,&nbsp;T. Seisen,&nbsp;S.F. Shariat,&nbsp;J. Teoh,&nbsp;E. Xylinas,&nbsp;O. Capoun,&nbsp;B.P. Rai,&nbsp;R.J. Sylvester","doi":"10.1016/j.euo.2026.05.005","DOIUrl":"10.1016/j.euo.2026.05.005","url":null,"abstract":"<div><h3>Background</h3><div>In non–muscle-invasive bladder cancer (NMIBC), the occurrence of a high-grade (HG) recurrence following Bacillus Calmette-Guérin (BCG) treatment identifies a disease category that is associated with a particularly poor prognosis and for which radical cystectomy (RC) is the gold standard. The latest definition of European Association of Urology (EAU) BCG-unresponsive disease has been endorsed by the United States Food and Drug Administration for clinical trials and adopted by EAU guidelines, despite limited clinical data supporting it.</div></div><div><h3>Objective</h3><div>To provide a clinical validation of the current EAU definitions of BCG failure.</div></div><div><h3>Design, setting, and participants</h3><div>This is an international retrospective multicenter study. Patients with NMIBC treated with at least five out of six BCG induction instillations after January 2000 and presenting with disease recurrence were included. The minimum allowed follow-up was 6 mo. Patients presenting with disease progression at 3 mo and those receiving RC prior to the first follow-up cystoscopy were excluded.</div></div><div><h3>Outcome measurements and statistical analysis</h3><div>The main objective of the study was to validate the prognostic value of the different categories of BCG failure, focusing on the EAU definitions of BCG-refractory, BCG-relapsing and BCG-unresponsive disease. The primary endpoint was the time to progression to muscle-invasive disease, the development of nodal disease or distant metastases. Patients were classified according to the EAU definitions of BCG failure, which were applied a priori and subsequently evaluated for their association with disease progression.</div></div><div><h3>Results and limitations</h3><div>Overall, 776 patients with recurrence after BCG were included. Of these, 448 (58%) experienced a HG recurrence. The BCG-refractory subgroups displayed the highest progression rates, the worst being represented by HG recurrence at 6 mo during BCG maintenance (46% progression at 5 yr), followed by T1HG recurrence at 3 mo (30% at 5 yr). BCG-relapsing disease showed a marginally more favorable outcome. Notably, early BCG recurrences included in the definition of BCG-unresponsive disease conveyed progression-free survival similar to BCG-refractory (35% at 5 yr), thus supporting their inclusion in this disease category.</div></div><div><h3>Conclusion</h3><div>We have provided the first clinical validation of the EAU definitions of BCG failure/unresponsive disease. They are prognostically informative and can be used to support clinical decision-making.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"9 4","pages":"Pages 868-882"},"PeriodicalIF":8.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981271","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}