Adjuvant Chemotherapy and Survival after Radical Cystectomy in Histologic Subtype Bladder Cancer

Objectives Patients with histologic subtype bladder cancer (HSBC) suffer worse outcomes than those with conventional urothelial carcinoma (UC). We sought to characterize the use of adjuvant chemotherapy (AC) in HSBC after radical cystectomy (RC) using the National Cancer Database (NCDB). Materials and Methods We retrospectively queried the NCDB (2006-2019) for patients with non-metastatic bladder cancer (BC) who underwent RC (N=45,797). Patients were stratified by histologic subtype and receipt of AC. Multivariable logistic regression determined associations of demographic and clinicopathologic features with receipt of AC. Multivariable Cox regression evaluated associations between receipt of any AC and overall survival (OS). Results We identified 4,469 patients with HSBC classified as squamous, adenocarcinoma, small cell, sarcomatoid, micropapillary, or plasmacytoid. Squamous comprised 31% of the HSBC cohort, followed by small cell and micropapillary. Black patients presented with a higher prevalence of adenocarcinoma (119/322, 37.0%). Use of AC was highest in plasmacytoid and small cell (30% each) and lowest in squamous (11%). Neuroendocrine histology was independently associated with greater odds of receiving AC (HR 1.6, 95%CI 1.37-1.87), while squamous cell histology was associated with lower odds (HR 0.61, 95%CI 0.53-0.71). On multivariable Cox regression analysis, treatment with AC was associated with significantly longer OS (HR 0.69, 95%CI 0.59-0.81) and for squamous, sarcomatoid, and micropapillary cohorts after stratified by subtype. Conclusions AC was variably used among patients with HSBC and was associated with OS benefit in such patients.