Trends in the use of neoadjuvant chemotherapy for bladder cancer with nonurothelial variant histology: An analysis of the National Cancer Database

Introduction: The aim of this study is to evaluate the trends in the use of neoadjuvant chemotherapy (NAC) over time (2006-2014) for patients diagnosed with muscle-invasive bladder cancer (MIBC) with nonurothelial variant histology (NUVH) in the National Cancer Database. Materials and Methods: We queried the NCDB for patients with muscle-invasive (i.e. cT2-4N0-3M0/X) urothelial carcinoma (UC) of the bladder. We examined demographic, clinical, and pathologic features associated with NAC, also substratifying into pure UC and NUVH. Tests of association were performed using Chi-square/Fisher's exact test for categorical variables and t-tests, ANOVA, or Kruskal-Wallis test for continuous variables. Outcomes were examined with Cox proportional hazards and 90-day mortality with the Kaplan-Meier method. Results: Totally 22,320 patients met our inclusion criteria, of whom 22.6% received NAC. The proportion of NAC increased significantly over time in the neuroendocrine and urothelial cell categories with 57.1% and 34.1% of patients in 2014 receiving NAC vs. 44% and 10.6% in 2006. No other variant histology showed a significant increase across the time sampled. Patients receiving NAC were more likely to have downstaging to pT0 (13.4% vs. 2.7%), negative surgical margin (89.1% vs. 86%), and pN0 (63.2% vs. 60.5%) and were less likely to have 30-day (1.4% vs. 3%) or 90-day (5% vs. 8.3%) mortality. Rates of downstaging to pT0 after NAC were similar among histologies. Conclusion: Neoadjuvant chemotherapy utilization continues to slowly increase in patients with MIBC. Patients with variant histology lag behind in terms of receiving NAC but appear to derive as much benefit as patients with pure urothelial cell bladder cancer.