To validate International Bladder Cancer Group (IBCG) definitions of Bacillus Calmette-Guérin (BCG)-unresponsive and BCG-exposed non-muscle-invasive bladder cancer (NMIBC) and assess prognostic heterogeneity across various BCG-failure types.
From a multicentre international cohort of 3806 BCG-treated patients, 591 who developed high-grade NMIBC recurrence following BCG between 2003 and 2024 were included. Progression-free survival (PFS) was the primary endpoint; cancer-specific (CSM) and overall mortality (OM) were secondary endpoints. Cumulative incidence functions, competing-risk models and multivariable Cox regression were used.
Patients with BCG-unresponsive and BCG-exposed disease showed similar PFS, CSM, and OM (all P > 0.05). When stratified into five subgroups, prognosis varied: 5-year progression rates were 29% for BCG-unresponsive, 32.5% for late relapse (between 6 and 24 months) after adequate BCG, 30% for BCG-exposed with inadequate BCG (<24 months from induction), 6.2% for BCG-resistant, and 14% for very late relapse (>24 months since last BCG) (P < 0.01). In multivariable analysis, BCG-exposed after inadequate BCG (subdistribution hazard ratio [sHR] 3.42, 95% confidence interval [CI] 1.33-8.84), late relapse (sHR 3.74, 95% CI 1.59-8.78), and BCG-unresponsive (sHR 2.34, 95% CI 1.00-5.44) were associated with higher progression risks compared to very late relapse. Limitations include retrospective design and treatment heterogeneity.
Under IBCG definitions, BCG-unresponsive and BCG-exposed NMIBC have similarly poor outcomes. A refined classification reveals prognostic heterogeneity, with late relapses after adequate BCG demonstrating outcomes comparable to BCG-unresponsive, and very late relapses conferring better prognosis.
BJU international. 2026 Mar 19 [Epub ahead of print]
Aleksander Ślusarczyk, Pietro Scilipoti, Roberto Contieri, Wojciech Krajewski, Francesco Claps, José Daniel Subiela, Laura S Mertens, Keiichiro Mori, Elisabeth Grobet-Jeandin, Jorge Caño Velasco, Karl Tully, Francesco Soria, Pedro Del Olmo Duran, Alfonso Lafuente Puentedura, Renee A G Lijnen, Mattia Longoni, Gautier Marcq, Andrea Mari, Ekaterina Laukhtina, Luca Afferi, Simone Albisinni, Andrea Gallioli, Francesco Del Giudice, Stephen A Boorjian, Alberto Briganti, Shahrokh F Shariat, Paolo Gontero, Piotr Radziszewski, Marco Moschini, Benjamin Pradere, European Association of Urology‐Young Academic Urologists (EAU‐YAU) , Urothelial Carcinoma Working Group
Department of General, Oncological and Functional Urology, Medical University of Warsaw, Warsaw, Poland., Department of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy., Department of Urology, National Cancer Institute, IRCCS Fondazione G. Pascale, Naples, Italy., Department of Urology and Oncologic Urology, Wrocław Medical University, Wrocław, Poland., Oncological Urology, Veneto Institute of Oncology IRCCS, Padua, Italy., Department of Urology, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain., Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan., Division of Urology, Geneva University Hospitals, Geneva, Switzerland., Department of Urology, Clínica Universidad de Navarra, Cancer Center, Pamplona, Spain., Department of Urology and Neurourology, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany., Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, Turin, Italy., Department of Urology, Gregorio Marañón University Hospital, Madrid, Spain., Department of Urology, Claude Huriez Hospital, CHU Lille, Lille, France., Department of Urology, Careggi Hospital, University of Florence, Florence, Italy., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Department of Urology, Aarau Kantonsspital, Aarau, Switzerland., Urology Unit, Department of Surgical Sciences, Policlinico Tor Vergata, Tor Vergata University, Rome, Italy., Department of Urology, Fundació Puigvert, Autonomous University of Barcelona, Barcelona, Spain., Department of Maternal Infant and Urologic Sciences, "Sapienza" University of Rome, Policlinico Umberto I Hospital, Rome, Italy., Department of Urology, Mayo Clinic, Rochester, MN, USA., Department of Urology UROSUD, La Croix Du Sud Hospital, Quint-Fonsegrives, France.