Outcomes in neuroendocrine bladder cancer treated with radical cystectomy.

Background: Management of localized or locally-advanced neuroendocrine (NE) bladder cancer is difficult as outcomes tend to be poor regardless of treatment. We sought to characterize our institutional experience to determine factors associated with survival. Methods: We utilized our bladder cancer database to identify patients with any NE component to their cancer who underwent radical cystectomy (RC) (1977-2012). Clinical and pathologic data were obtained. Kaplan-Meier curves estimated recurrence-free survival (RFS) and overall survival (OS) and were compared with the log rank test. Multivariable Cox proportional hazards determined factors associated with RFS and OS. Results: A total of 86 patients met the inclusion criteria with a median age of 68 years (range 37-89). The highest clinical stage prior to RC was ≤ T2 in 71 patients, > T2 in 8 patients, and lymph node positive in 7 patients. There were 35 (41 %) patients with predominant NE histology (small cell n = 30, large cell n = 5) and the remaining 51 (59%) patients had < 50% NE components on histology. Twenty-two patients (26%) underwent neoadjuvant chemotherapy (NAChT) with cisplatin/etoposide representing the most common regimen. Lymph node upstaging was significantly higher in patients who did not receive NAChT when compared with patients who receive NAChT (51 % vs. 19%, p < 0.02). The median OS and RFS for the entire cohort were 2.0 and 1.4 years, respectively. Patients with predominant NE histology had worse OS when compared with patients with < 50% NE histology (p = 0.002). A response to NAChT on imaging was associated with improved OS when compared with patients who had no response to NAChT (median 31 months vs. 10 months, p = 0.13). On multivariable analysis, a predominant NE histology, presence of pathologic upstaging, and not receiving adjuvant chemotherapy were independently associated with worse OS. Conclusions: Survival in patients with bladder cancer with NE histology is poor and occult LN positive disease is identified in almost half of patients at the time of RC. A predominant NE histology is independently associated with worse survival. Further investigation into the optimal timing of multimodal therapies is required to improve outcomes in this population.