Small cell carcinoma of the bladder (SCCB): Clinical, histopathologic, and genomic predictors of clinical outcomes.

Abstract

294 Background: SCCB is a rare, aggressive subtype of bladder cancer. We reviewed our center’s experience in SCCB management and investigated potential markers of clinical outcomes. Methods: SCCB cases were identified and re-reviewed for confirmation by detailed histologic evaluation. A subset of SCCB was sequenced with MSK-IMPACT ( > 279 genes) (Cheng et al J Mol Diagn 2015). Clinical stage, treatment response and proportion of neuroendocrine component (%NE) were correlated with progression-free (PFS) and overall survival (OS), calculated from the time of cystectomy. Distribution of somatic alterations (alts) was compared between responders ( ≤ ypT1pN0) and nonresponders. Results: Between 1985 and 2015, 214 SCCB patients (pts) were identified. Median age was 68 years (range: 38 – 94) and 78% were male. Of 199 pts with sufficient data, 147 (74%) were nonmetastatic (M0) and 52 pts (26%) had metastatic disease (M1). 14 pts did not receive SCCB-directed therapies. Of M0 pts, 108 underwent cystectomy: 71 received neoadjuvant (NAC), 14 received adjuvant, 14 had definitive chemoradiotherapy and 23 did not receive chemotherapy. Of M1 pts, 47 received chemotherapy. Cystectomy only pts were older than NAC pts (76 vs 67 years, p < .01). NAC improved PFS and OS compared to cystectomy only (HR 0.55, p = .04 and HR 0.41, p < .01) although only OS remains significant after adjusting for age (p = .01). For NAC pts, pT0pN0 and ≤ pT1pN0 rates were 38% and 48%, respectively. Responders had superior PFS (HR 0.26 p < .01) and OS (HR 0.32 p = .02). Median %NE was 100 (range: 10 – 100) and did not correlate with NAC response. %NE ≥ 95 is more prevalent among M1 pts (85% vs 68%, p = .04). Genomic data were available for 31 NAC pts (44%). Responders were enriched with alts in ERBB2 (33% vs. 0%, p = .02), PI3K pathway ( PIK3CA, PTEN, AKT1, TSC1, TSC2) (33% vs. 6%, p = .02) and histone acetyltransferases (60% vs. 25%, p = .07). Of 22/31 tumors sequenced with a larger gene set (n = 341), ERCC2 and RBM10 alts were enriched in responders (54% vs. 11%, p = .07) and nonresponders (44% vs. 0%, p = .02), respectively. Conclusions: In SCCB, NAC improves survival and response might be characterized by specific somatic alts. M1 pts had higher %NE but it is not predictive of outcome.