A Single Institution Experience in the Management of Localized Neuroendocrine Carcinoma of the Bladder

Background Neuroendocrine carcinoma of the bladder (NEC-bladder) is a rare disease associated with poor outcomes in the setting of heterogenous histologic classifications and variable treatment approaches. Materials and Methods Patients with localized NEC-bladder treated with surgery or radiation between 2001-2021 were retrospectively identified. Rates of pathologic complete response (pCR; ypT0) and downstaging were evaluated following NAC in surgically-treated patients. Progression-free survival (PFS) and overall survival (OS) were analyzed with univariable (log-rank) and multivariable (MVA; Cox regression) methods. Results Sixty-five patients were included. Majority were male (87.7%) and the median age was 73. The distribution of tumor histology was small cell (64.6%) or urothelial with Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation NE differentiation (35.4%). Most patients (69.2%) received NAC, predominantly platinum/etoposide. Patients were treated with definitive local therapy by surgery (78.5%) or chemoradiation (21.5%). The majority (62.7%) of surgical patients had pT2 or greater disease with 37.3% having pN+. The pCR and downstaging rates were 21.6% and 35.1%, respectively. With median follow-up of 60 months (m), 50.7% of patients had recurrence, leading to a median PFS and OS of 16.4m and 25.9m, respectively. Receipt of NAC was associated with improved PFS (p=0.04) and downstaging improved PFS (p=0.012) and OS (p<0.001). Patients receiving NAC with ypN0 had median OS of 69.9m vs 15.3m in those with ypN+ (p<0.001). MVA identified receipt of NAC and pN as predictors of PFS; pN was the only predictor of OS. Notably, no differences in PFS or OS were seen between histology of primary tumor (small cell vs NE differentiation) or pathologic lymph nodes (NE alone [31.6%], pure urothelial [47.4%], or mixed [21.1%]. The brain metastasis rate was 10.8% with all patients having small cell histology. Conclusions Optimized therapy in NEC-bladder includes NAC followed by local consolidation. Ascertainment of ypN0 is associated with long term survival, while pN+remains associated with poor outcomes. Microabstract We performed a retrospective analysis of 65 patients with localized primary neuroendocrine cancers arising from the bladder and describe oncologic outcomes, prognostic factors, and identify predictors of pathologic response to neoadjuvant chemotherapy. To our knowledge, our study is the first to evaluate outcomes related to the histology of pathologically-involved lymph nodes, in which we found no significant differences. We further found that patients with residual ypN+ disease or no pathological response following neoadjuvant chemotherapy may derive benefit from adjuvant chemotherapy. When comparing the primary surgical cohort vs those that underwent bladder preservation with radiotherapy, we found no significant differences in various endpoints.