Dedicated tools estimating the risk of Bacillus Calmette-Guérin (BCG) failure among patients with high-grade (HG) non-muscle-invasive bladder cancer (NMIBC) are lacking.
To develop a risk model predicting the development of BCG-unresponsive disease (defined according to the International Bladder Cancer Group and European Association of Urology [EAU] guidelines) or progression in patients with HG NMIBC receiving adequate BCG therapy.
This retrospective multicenter study included 2211 patients who were BCG naïve with HG Ta/T1 NMIBC (±carcinoma in situ [CIS]) treated with adequate BCG therapy between January 2003 and December 2024 at 13 academic centers.
The primary end point was time to BCG-unresponsive disease or progression to muscle-invasive/metastatic cancer. Multivariable Cox regression identified independent predictors, and a weighted clinical risk score stratified patients into four risk groups.
Independent risk factors included T1 stage (adjusted hazard ratio [aHR] 1.52, 95% confidence interval [CI] 1.10-2.11), persistent HG or T1 tumor at restaging transurethral resection (aHR 2.51, 95% CI 2.06-3.06), multifocality (aHR 1.46, 95% CI 1.22-1.74), concomitant CIS (aHR 1.46, 95% CI 1.21-1.77), and World Health Organization 1973/2004/2016 HG/grade 3 (aHR 1.56, 95% CI 1.24-1.94). Internal validation via 1000 bootstrap samples revealed minimal optimism (0.01) and good calibration. The model demonstrated superior discrimination compared with the European Organization for Research and Treatment of Cancer progression score and EAU 2021 stratification (Harrell concordance index 0.68 vs 0.61 vs 0.56); 5-yr BCG-unresponsive-free survival was 88%, 79%, 60%, and 49%, respectively, across increasing risk groups.
We developed a risk stratification model for patients with HG Ta/T1 treated with adequate BCG therapy. This tool enables individualized assessment of BCG failure risk and may support clinical decision-making.
European urology oncology. 2026 Jun 25 [Epub ahead of print]
Aleksander Ślusarczyk, Marco Moschini, Wojciech Krajewski, Pietro Scilipoti, Roberto Contieri, Francesco Claps, José Daniel Subiela, Laura S Mertens, Keiichiro Mori, Jorge Caño Velasco, Francesco Soria, Elisabeth Grobet-Jeandin, Karl Tully, Karolina Garbas, Pedro Del Olmo Durán, Renee A G Lijnen, Giorgia Fertitta, Maxence Reynard, Olga Katzendorn, Alfonso Lafuente Puentedura, Mattia Longoni, David D'Andrea, Francesco Del Giudice, Andrea Gallioli, Ekaterina Laukhtina, Gautier Marcq, Andrea Mari, Luca Afferi, Simone Albisinni, Antonio Amodeo, Stephen A Boorjian, Alberto Briganti, Francesco Montorsi, Shahrokh F Shariat, Paolo Gontero, Piotr Radziszewski, 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. Electronic address: ., Department of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy., Department of Urology and Oncologic Urology, Wrocław Medical University, Wroclaw, Poland., Department of Urology, National Cancer Institute, IRCCS Fondazione G. Pascale, Naples, Italy., Oncological Urology, Veneto Institute of Oncology, 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., Department of Urology, Clínica Universidad de Navarra, Cancer Center, Pamplona, Spain., Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, Turin, Italy., Division of Urology, Geneva University Hospitals, Geneva, Switzerland., Department of Urology and Neurourology, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany., Department of General, Oncological and Functional Urology, Medical University of Warsaw, Warsaw, Poland., Department of Urology, UROSUD, La Croix Du Sud Hospital, Quint-Fonsegrives, France., Department of Urology, Gregorio Marañón University Hospital, Madrid, Spain., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Department of Maternal, Infant, and Urologic Sciences, "Sapienza" University of Rome, Policlinico Umberto I Hospital, Rome, Italy., Department of Urology, Fundació Puigvert, Autonomous University of Barcelona, Barcelona, Spain., Department of Urology, Claude Huriez Hospital, Centre Hospitalier Universitaire (CHU) Lille, Lille, France., Department of Urology, University of Florence, Careggi Hospital, Florence, Italy., Department of Urology, Aarau Kantonsspital, Aarau, Switzerland., Urology Unit, Department of Surgical Sciences, Policlinico Tor Vergata, Tor Vergata University, Roma, Italy., Department of Urology, Mayo Clinic, Rochester, MN, USA., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, University of Texas Southwestern, Dallas, TX, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Department of Urology, Semmelweis University, Budapest, Hungary.