Tumor size effect on cancer-specific mortality in T2N0M0 urothelial bladder cancer treated with trimodal therapy

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.