Adjuvant Chemotherapy vs Observation for Patients With Adverse Pathologic Features at Radical Cystectomy Previously Treated With Neoadjuvant Chemotherapy.

Importance: Despite existing evidence of a benefit associated with cisplatin-based adjuvant chemotherapy (AC) after radical cystectomy (RC) for chemotherapy-naive patients with pT3/T4 and/or pN+ urothelial carcinoma of the bladder (UCB), to our knowledge, no studies have addressed the effectiveness of AC in those who received neoadjuvant chemotherapy (NAC) before surgery. Objective: To assess the comparative effectiveness of AC vs observation for patients with pT3/T4 and/or pN+ UCB previously treated with NAC and RC. Design, Setting, and Participants: This observational cohort study used the National Cancer Data Base (January 1, 2006, through December 31, 2012) to identify individuals who received NAC and RC followed by AC or observation for pT3/T4 and/or pN+ UCB. Main Outcomes and Measures: After multiple imputation was used to handle missing data, inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier and Cox proportional hazards regression analyses were performed with a 6-month conditional landmark to compare overall survival (OS) among patients who received NAC and RC followed by AC vs observation. In addition, exploratory analyses were conducted to examine the heterogeneity of the treatment effect according to age (continuous), sex (female vs male), Charlson comorbidity index (≥1 vs 0), pT/N stage (pT3/T4N0 vs pTanyN+), and surgical margin status (positive vs negative) by testing interaction terms within the IPTW-adjusted Cox proportional hazards regression model. Results: Of the 788 patients with pT3/T4 and/or pN+ UCB (mean [SD] age, 65.3 [9.4] years; 603 [76.5%] male and 185 [23.5%] female), 184 (23.4%) received NAC and RC followed by AC and 604 (76.6%) received NAC and RC followed by observation. The 6-month conditional landmark, IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for NAC and RC followed by AC (29.9 months; interquartile range, 15.1-85.4 months) vs NAC and RC followed by observation (24.2 months; interquartile range, 12.9-58.9 months) (P = .046). The 5-year IPTW-adjusted rates of OS were 36.8% for NAC and RC followed by AC vs 24.7% for NAC and RC followed by observation. In the IPTW-adjusted Cox proportional hazards regression analysis, NAC and RC followed by AC was associated with a significant OS benefit (hazard ratio, 0.78; 95% CI, 0.61-0.99; P = .046). Interaction term analyses indicated that the OS benefit of NAC and RC followed by AC decreased significantly with age (hazard ratio, 0.97; 95% CI, 0.95-0.99; P = .02), whereas no significant interaction was observed with sex (P = .82), Charlson comorbidity index (P = .51), pT/N stage (P = .95), and surgical margin status (P = .29). Conclusions and Relevance: This study found that AC after NAC and RC may be associated with an OS benefit for patients with pT3/T4 and/or pN+ UCB. The present findings should be considered as preliminary evidence to conduct a randomized clinical trial to address this association