Impact of systemic therapy on clinical T1 small-cell neuroendocrine carcinoma of the bladder

The purpose of this study was to analyze survival outcomes and pathologic response of patients with cT1N0 small-cell neuroendocrine carcinoma (SCNEC) of the bladder treated with neoadjuvant chemotherapy (neoCTX). All cases of bladder SCNEC treated at our institution from January 1996 to July 2023 were identified. cT1N0 was defined as transurethral resection pathology showing lamina propria invasion with present and uninvolved muscularis propria. Pathologic downstaging and recurrences were evaluated. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Cox regression and Kaplan–Meier method. A total of 30 patients with cT1N0 bladder SCNEC were included. Median follow-up was 88 months [95% confidence interval (CI) 44-131 months]. NeoCTX was given to 21 (70%) patients with a median of 4 cycles (range 1-6 cycles). A total of 27 (90%) patients received definitive local therapy. In cT1 bladder SCNEC, neoCTX was associated with decreased odds of pathologic upstaging [odds ratio = 0.07 (95% CI 0.01-0.45), P = 0.004], decreased odds of relapse [odds ratio = 0.12 (95% CI 0.02-0.65), P = 0.01], improved DFS [hazard ratio (HR) 0.30, 95% CI 0.09-0.96, P = 0.04], and improved OS (HR 0.32, 95% CI 0.10-1.02, P = 0.05). Compared with cT2N0 treated with neoCTX, cT1N0 treated with neoCTX had improved median DFS (HR 0.44, 95% CI 0.19-1.03, P = 0.05) and improved median OS (HR 0.52, 95% CI 0.22-1.24, P = 0.14). NeoCTX had suggestive benefit in patients with cT1 bladder SCNEC with decreased odds of pathologic upstaging, metastatic relapse, and improved survival. •This research addresses a significant gap in the literature on treating cT1N0 SCNEC of the bladder.•Neoadjuvant chemotherapy was associated with decreased odds of pathologic upstaging and metastatic relapse.•Provides an informed treatment approach for cT1 bladder SCNEC from a cohort with pathologic review and long-term follow-up.