Introduction

Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the standard of care for clinically localized muscle-invasive urothelial carcinoma of the bladder (UCB). Approximately 20% of patients who received NAC + RC have adverse features on pathology, specifically pT3-4 and/or N+ disease. Against this backdrop, we examine the role of adjuvant chemotherapy (AC) following RC for those pretreated with NAC.

Methods

Within the National Cancer Data Base (2004-2012), we identified 800 patients who received AC vs. observation following NAC plus RC for pT3/T4N0 or pN+ UCB. Multiple imputation using chained equations was used to handle missing data. We further performed inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier and Cox regression analyses with a 6-month conditional landmark to compare overall survival (OS) between the two treatment groups. Specifically, propensity scores derived from a logistic regression model predicting the receipt of AC vs. observation were used to weigh each patient to balance observable characteristics.

Results

Overall, 190 (23.8%) vs. 610 (76.2%) patients underwent AC vs. observation following NAC + RC, respectively. Independent predictors of receiving AC vs. observation included facility type (Non-academic vs. academic: OR=2.08, 95%CI=[1.45-2.97]; P<0.001) and location (West vs. Est; OR=1.84; 95%CI=[1.12-3.01]; P=0.016), as well as disease stage (pTanyN+ vs. pT3N0: OR=2.18; 95%CI=[1.47-3.22]; P<0.001), while older age (OR=0.97; 95%CI=[0.94-0.99]; P=0.008) predicted the opposite. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly improved in the AC vs. observation group (29.9 [IQR, 15.1-85.4] vs. 24.2 [IQR, 12.9-58.9] months; P=0.031; Figure 1). The 5-year IPTW-adjusted rates of OS for AC vs. observation were 36.8% vs. 24.7%, respectively. In IPTW-adjusted Cox regression analyses, AC was associated with a significant OS benefit (HR=0.76; 95%CI=[0.60-0.97]; P=0.031).

Conclusions

We report an OS benefit for individuals treated with AC vs. observation for pT3-4 and/or N+ UCB following NAC + RC. Our findings warrant further consideration in randomized controlled trials to explore this hypothesis.

Funding

none