Treatment Patterns and Survival Outcomes of Patients With Small Cell Carcinoma of the Bladder: A National Cancer Database Analysis

Abstract

Small cell carcinoma of the bladder (SCCB) is an aggressive neuroendocrine tumor that is associated with poorer outcomes than transitional cell carcinoma. Given the rarity of SCCB, there is no standard treatment algorithm. Many treatment strategies are largely extrapolated from small cell lung cancer, but surgical resection, specifically radical cystectomy (RC), remains a widely utilized treatment modality. We queried the National Cancer Database (NCDB) to assess treatment patterns and outcomes in this rare disease, and compared outcomes of RC with multimodality therapy for bladder preservation. We identified all SCCB cases in the NCDB diagnosed between 2004 and 2013. Inclusion criteria included cT1-4a N0 M0 with a pathologic diagnosis of SCCB and complete staging and treatment details available. Treatment groups included: no further treatment, chemotherapy alone (CT), radiation therapy alone (RT), combined chemoradiation therapy (CRT), RC alone, and RC plus chemotherapy (RC+C). Only patients receiving RT to the bladder or pelvis (>3000cGy) were considered in the RT groups. Overall survival (OS) was estimated by the Kaplan-Meier survival method, and log-rank and Cox analysis was used for univariate and multivariate analysis. A total 894 cases met inclusion criteria for analysis. Mean age was 72.0 years (range: 31 – 90). 695 (77.8%) patients were male. Mean follow-up was 26.5 months (range: 0.0 – 131.6). 677 (75.7%) of patients had Stage II or III disease. The most common treatment modality was CT alone (235 patients; 26.3%) followed by CRT (220 patients; 24.6%) and RC+C (206 patients; 23%). 139 patients (15.5%) had no further treatment after TURBT and 94 patients (10.6%) had either RT or RC alone without CT. The mean OS of the entire cohort was 44.0 months (95% CI, 40.4 –47.6). OS was significantly less for CT alone (38.9 months, 95% CI: 32.7-45.2) compared to both CRT (54.9 months, 95% CI: 47.3.7-62.4) and RC+C (56.9 months, 95% CI: 49.0-64.8) (P<0.0001). OS between CRT and RC+C was not significantly different (P=0.42). The mean age of those receiving CRT was 72.4 years versus 65.43 years for those receiving RC+C (P<0.001). Multivariate analysis controlling for age, stage, sex, race, year of diagnosis, facility type, facility location, and Charlson/Deyo Score showed improved OS for both CRT and RC+C (HR 0.42; 95% CI, 0.33-0.54; P <0.0001) and (HR 0.45; 95% CI, 0.34 – 0.59; P <0.001), respectively. Both RC+C and CRT are associated with improved OS compared to CT alone, RT alone, and RC alone for SCCB. Those undergoing CRT tended to be older than the surgery group. There is no significant difference in OS following RC+C or bladder preservation with CRT.