Adjuvant chemotherapy versus observation following radical cystectomy for locally advanced urothelial carcinoma of the bladder.

Background: The role of adjuvant chemotherapy (AC) in patients with locally advanced bladder cancer following radical cystectomy (RC) remains uncertain, with contemporary clinical trials underpowered and closed early due to low accrual.

Objective: To conduct observational analyses designed to emulate a completed randomized trial of AC in patients with locally advanced bladder cancer.

Design, Settings, And Participants: Based on EORTC 30994 eligibility criteria, we identified adult patients aged 35 to 75 with pT3/pT4 Nany M0 or Tany pN1-3 M0, R0 urothelial carcinoma of the bladder treated with RC and lymphadenectomy from 2006 to 2015 in the National Cancer Database.

Outcome Measurements And Statistical Analysis: A propensity score for receipt of AC within 3 months of RC was estimated, and the associations of AC with overall survival were evaluated after reweighting by stabilized inverse probability of treatment weights.

Results: Of the 2,416 patients who met inclusion criteria, 945 (39%) received AC after RC. After propensity score adjustment, baseline characteristics were well-balanced. Median follow-up was 26.0 months. After IPW-reweighting, overall survival was 43% vs. 36% at 5-years and 34% vs. 24% at 10-years, among those who did and did not receive AC, respectively (P < 0.01). In IPW-adjusted Cox regression models, AC was associated with improved all-cause mortality (HR 0.71; 95% CI 0.63-0.81; P < 0.01). Estimates were overall consistent in analyses that examined heterogeneity of treatment effects. Limitations include unmeasured confounding, selection bias, and lack of baseline renal function data.

Conclusion: In observational analyses designed to emulate EORTC 30994, AC was associated with improved overall survival compared to observation after RC. Results were consistent across baseline patient and tumor characteristics.