Outcomes for Muscle-invasive Bladder Cancer with Radical Cystectomy or Trimodal Therapy in US Veterans

BACKGROUND: Muscle-invasive bladder cancer (MIBC) remains undertreated despite multiple potentially curative options. Both radical cystectomy (RC) with or without neoadjuvant chemotherapy and trimodal therapy (TMT), including transurethral resection of bladder tumor followed by chemoradiotherapy, are standard treatments. OBJECTIVE: To evaluate real-world clinical outcomes of RC with neoadjuvant chemotherapy (RC-NAC), RC without NAC, TMT with National Comprehensive Cancer Network guideline–preferred radiosensitizing chemotherapy including cisplatin or mitomycin-C and 5-fluorouracil (pTMT), and TMT with nonpreferred chemotherapy (npTMT). DESIGN, SETTING, AND PARTICIPANTS: US veterans with nonmetastatic MIBC (T2-4aN0-3M0) were studied. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall mortality (OM) was evaluated with multivariable Cox proportional hazard model. Bladder cancer-specific mortality (BCSM) was evaluated with multivariable Fine-Gray regression. Salvage cystectomy rates were obtained by chart review. RESULTS AND LIMITATIONS: Overall 2306 patients were included: 1472 (64%) with RC without NAC, 506 (22%) with RC-NAC, 163 (7%) with pTMT, and 165 (7%) with npTMT. On multivariable analysis, pTMT was associated with similar OM (hazard ratio [HR] 1.19; 95% confidence interval [CI] 0.94–1.50; p = 0.15) and BCSM (HR 1.34; 95% CI 0.99–1.83; p = 0.06) to RC-NAC; npTMT was associated with worse OM (HR 1.30; 95% CI 1.04–1.61; p = 0.02) and BCSM (HR 1.45; 95% CI 1.09–1.94; p = 0.01). RC without NAC was associated with similar OM (HR 1.08; 95% CI 0.95–1.24; p = 0.24) and BCSM (HR 1.02; 95% CI 0.86–1.21; p = 0.79). When stratified by age, among patients ≥65 yr of age, treatment with pTMT was associated with similar OM (HR 1.14; 95% CI 0.87–1.50; p = 0.35) and BCSM (HR 1.11; 95% CI 0.76–1.62; p = 0.60). Among patients <65 yr of age, pTMT was associated with worse OM (HR 1.82; 95% CI 1.14–2.91; p = 0.01) and BCSM (HR 2.51; 95% CI 1.52–4.13; p < 0.01). The 5-yr cumulative incidence of salvage cystectomy in the TMT group was 3.6%. CONCLUSIONS: In MIBC, patients receiving pTMT have comparable survival in RC-NAC patients ≥65 yr and inferior survival in RC-NAC patients <65 yr. Salvage cystectomy rates were low. PATIENT SUMMARY: Management of muscle-invasive bladder cancer is a multidisciplinary effort requiring thoughtful discussions with patients about treatment options, including trimodal therapy, which is an effective treatment option.