Current guidelines recommend trimodal therapy (TMT) for muscle-invasive bladder cancer when complete visible transurethral resection is feasible, but no specific tumor size cutoff is defined. We evaluated the impact of tumor size on cancer-specific mortality (CSM) in T2N0M0 urothelial bladder cancer treated with TMT.
Using the Surveillance, Epidemiology, and End Results database (2004-2022), pT2N0M0 urothelial bladder cancer patients treated with TMT were identified. Sequential testing of tumor size cutoffs of 3, 4, 5, 6, and 7 cm were applied. Propensity score matching and multivariable competing risks regression (CRR) models were used.
Among 3,014 included pT2N0M0 urothelial bladder cancer patients treated with TMT, tumor size ranged from 0.3 to 10.0 cm (median 4.0 cm). In multivariable CRR models, each tested cutoff independently predicted higher CSM, except for at 3 cm. Multivariable CRR-derived hazard ratios (HR) for cutoffs of 4, 5, 6, and 7 cm were respectively 1.23, 1.28, 1.72, and 2.22 (all P < 0.05). Applying established and recommended noninferiority margins in oncology trials of up to 30% suggests that tumor size cutoff of 6 cm (HR 1.72) could represent a clinically meaningful criterion used in patient selection for TMT. Limitations include retrospective design and lack of data on comorbidities and treatment specifics.
Tumor size is directly proportional to CSM rate in pT2N0M0 urothelial bladder cancer treated with TMT. A tumor size cutoff of 6 cm (HR 1.72) could represent a clinically meaningful criterion used in patient selection for TMT when the intent of avoiding excess CSM represents the endpoint of interest.
Urologic oncology. 2026 Mar 22 [Epub ahead of print]
Nick J Lee, Federico Polverino, Leonardo Quarta, Maximilian Filzmayer, Michele Petix, Jordan A Goyal, Nicola Longo, Gennaro Musi, Felix K H Chun, Alberto Briganti, Shahrokh F Shariat, Fred Saad, Pierre I Karakiewicz
Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada. Electronic address: ., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, Naples, Italy., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Urology, Vita-Salute San Raffaele University, Milan, Italy., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Goethe University Frankfurt, University Hospital, Department of Urology, Frankfurt am Main, Germany., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Department of Urology, IEO European Institute of Oncology, IRCCS, Milan, Italy; Department of Urology, Universitàdegli Studi di Milano, Milan, Italy., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada., Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, Naples, Italy., Department of Urology, IEO European Institute of Oncology, IRCCS, Milan, Italy., Goethe University Frankfurt, University Hospital, Department of Urology, Frankfurt am Main, Germany., Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Weill Cornell Medical College, New York, New York; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan.