Survival Rates in Trimodal Therapy Versus Radiotherapy in Urothelial Carcinoma of Urinary Bladder

Background and objective: Trimodal therapy (TMT) provided significant survival advantage relative to external beam radiation therapy (EBRT) alone in prospective trials. However, the magnitude of survival benefit has not been validated in population-based studies. The objective of this study is to determine whether TMT is associated with lower cancer-specific mortality (CSM) rates relative to EBRT. Methods: Within the Surveillance, Epidemiology, and End Results database (2004–2020), we identified patients with cT2-T4aN0M0 urothelial carcinoma of urinary bladder (UCUB) treated with either TMT or EBRT. Cumulative incidence plots and multivariable competing risk regression (CRR) models addressed CSM after additional adjustment for other-cause mortality and standard covariates. The same methodology was repeated according to stage and age categories. Key findings and limitations: Of 4471 patients, 3391 (76%) underwent TMT versus 1080 (24%) EBRT. TMT rates increased over time in the overall cohort (estimated annual percent change [EAPC]: 1.8%, p < 0.001) as well as in organ-confined (OC) stage (EAPC: 1.7%, p < 0.001), but not in non–organ-confined (NOC) stage (p = 0.051). In the overall cohort, 5-yr CSM rates were 43.6% in TMT versus 52.7% in EBRT. In multivariable CRR models, TMT was an independent predictor of lower CSM (hazard ratio [HR]: 0.76, p < 0.001). In OC patients, 5-yr CSM rates were 42.0% in TMT versus 51.9% in EBRT (p < 0.001). In multivariable CRR models, TMT was an independent predictor of lower CSM (HR: 0.74, p < 0.001). Conversely, in NOC patients, TMT did not achieve independent predictor status (p = 0.3). Conclusions and clinical implications: In this population-based study, relative to EBRT, TMT is associated with lower CSM in OC stage, but not in NOC UCUB patients. Patient summary: In this report, we investigated the survival benefit of administering systemic chemotherapy in addition to radiotherapy in patients who are candidates for bladder-sparing strategies. We found that the combination of systemic chemotherapy and radiotherapy leads to improved cancer-specific survival compared with radiotherapy alone in patients with organ-confined urothelial carcinoma. We conclude that among patients who are candidates for bladder-sparing strategies, following transurethral resection, the combination of radiotherapy and chemotherapy (namely, trimodal therapy) should always be offered in those with organ-confined urothelial carcinoma.