Effectiveness of Adjuvant Chemotherapy After Radical Cystectomy for Locally Advanced and/or Pelvic Lymph Node-Positive Muscle-invasive Urothelial Carcinoma of the Bladder: A Propensity Score-Weighted Competing Risks Analysis

Abstract

Background: The benefit of adjuvant chemotherapy (AC) for muscle-invasive urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC) is controversial.

Objective: To assess the effectiveness of AC after RC for muscle-invasive UCB in contemporary European routine practice.

Design, setting, and participants: By using a prospectively collected European multicenter database, we compared survival outcomes between patients who received AC versus observation after RC for locally advanced (pT3/T4) and/or pelvic lymph node-positive (pN+) muscle-invasive UCB in 2011.

Intervention: AC versus observation after RC.

Outcome measurements and statistical analysis: Inverse probability of treatment weighting (IPTW)-adjusted Cox regression and competing risks analyses were performed to compare overall survival (OS) as well as cancer-specific and other-cause mortality between patients who received AC versus observation.

Results and limitations: Overall, 224 patients who received AC (n = 84) versus observation (n = 140) were included. The rate of 3-yr OS in patients who received AC versus observation was 62.1% versus 40.9%, respectively (p = 0.014). In IPTW-adjusted Cox regression analysis, AC versus observation was associated with an OS benefit (hazard ratio: 0.47; 95% confidence interval [CI]: 0.25-0.86; p = 0.014). In IPTW-adjusted competing risks analysis, AC versus observation was associated with a decreased risk of cancer-specific mortality (subhazard ratio: 0.51; 95% CI: 0.26-0.98; p = 0.044) without any increased risk of other-cause mortality (subhazard ratio: 0.48; 95% CI: 0.14-1.60; p = 0.233). Limitations include the relatively small sample size as well as the potential presence of unmeasured confounders related to the observational study design.

Conclusions: We found that AC versus observation was associated with a survival benefit after RC in patients with pT3/T4 and/or pN+ UCB. These results should encourage physicians to deliver AC and researchers to pursue prospective or large observational investigations.

Patient summary: Overall survival and cancer-specific survival benefit was found in patients who received adjuvant chemotherapy relative to observation after radical cystectomy for locally advanced and/or pelvic lymph node-positive bladder cancer.

Keywords: Adjuvant chemotherapy; Cystectomy; Propensity score; Survival; Urinary bladder neoplasms.