Impact of selection bias on outcomes in veterans with muscle-invasive bladder cancer receiving bladder preserving trimodality therapy.

Abstract

462 Background: Retrospective studies using large registries comparing outcomes between radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) to trimodality therapy (TMT), which includes transurethral resection of bladder tumor followed by chemoradiation, often cannot distinguish whether patients receiving TMT were eligible for cystectomy but declined or simply ineligible for cystectomy. The objective of this study was to compare survival outcomes of patients with MIBC receiving TMT stratified by whether they were cystectomy-eligible to patients receiving RC +/- NAC. Methods: We used the national Veterans Affairs’ (VA) database to identify patients diagnosed between 2000-2017 with urothelial histology, MIBC (T2-4a/N0-3/M0) who underwent RC or TMT. Overall survival (OS) was evaluated with multivariable Cox proportional hazards model. Bladder cancer-specific mortality (BCSM) was evaluated with multivariable Fine-Gray regression. We conducted a chart review of clinical notes to ascertain if patients were eligible for cystectomy. Results: Overall 2306 Veterans with MIBC were included: 1472 (64%) with RC without NAC, 506 (22%) with RC-NAC, 107 (4.6%) with TMT eligible for RC, and 221 (9.4%) with TMT ineligible for RC. Median follow up time was 4.7 years. Patients receiving RC were on average 10 years younger, had higher creatinine clearance, and fewer comorbidities than those receiving TMT. Cystectomy-eligible TMT patients had higher creatinine clearance and fewer comorbidities than those ineligible for cystectomy. On multivariable analysis, compared to RC-NAC, TMT in cystectomy-eligible patients was associated with similar OS (hazard ratio [HR] 0.99; 95% confidence interval [CI] 0.76 - 1.28; p = 0.93) and BCSM (HR 1.02; 95% CI 0.71-1.47; p = 0.91). Compared to RC-NAC, TMT in cystectomy-ineligible patients was associated with inferior OS (HR 1.39; 95% CI 1.13 - 1.71; p = 0.002) and BCSM (HR 1.61; 95% CI 1.23 - 2.10; p < 0.001). Conclusions: There is a significant selection bias among patients with MIBC receiving TMT. Cystectomy-eligible patients receiving TMT likely have similar survival outcomes as those receiving RC. Comparisons between RC and TMT in large registry data that lack information regarding eligibility for cystectomy in the TMT arm may be unreliable.