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

Journal Article (Journal Article)


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.


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%.


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.

Full Text

Duke Authors

Cited Authors

  • Kumar, A; Cherry, DR; Courtney, PT; Nalawade, V; Kotha, N; Riviere, PJ; Efstathiou, J; McKay, RR; Karim Kader, A; Rose, BS; Stewart, TF

Published Date

  • August 2021

Published In

Volume / Issue

  • 30 /

Start / End Page

  • 1 - 10

PubMed ID

  • 34337540

Pubmed Central ID

  • PMC8317783

Electronic International Standard Serial Number (EISSN)

  • 2666-1683

International Standard Serial Number (ISSN)

  • 2666-1691

Digital Object Identifier (DOI)

  • 10.1016/j.euros.2021.05.009


  • eng