Synapse - Long-term outcomes of local and metastatic small cell carcinoma of the urinary bladder and genomic analysis of patients treated with neoadjuvant chemotherapy

Long-term outcomes of local and metastatic small cell carcinoma of the urinary bladder and genomic analysis of patients treated with neoadjuvant chemotherapy Journal Article

Authors:	Teo, M. Y.; Guercio, B. J.; Arora, A.; Hao, X.; Regazzi, A. M.; Donahue, T.; Herr, H. W.; Goh, A. C.; Cha, E. K.; Pietzak, E.; Donat, S. M.; Dalbagni, G.; Bochner, B. H.; Olgac, S.; Sarungbam, J.; Sirintrapun, S. J.; Chen, Y. B.; Gopalan, A.; Fine, S. W.; Tickoo, S. K.; Reuter, V. E.; Weigelt, B.; Schultheis, A. M.; Funt, S. A.; Bajorin, D. F.; Solit, D. B.; Iyer, G.; Ostrovnaya, I.; Rosenberg, J. E.; Al-Ahmadie, H.
Article Title:	Long-term outcomes of local and metastatic small cell carcinoma of the urinary bladder and genomic analysis of patients treated with neoadjuvant chemotherapy
Abstract:	Introduction: Small cell carcinoma of the bladder (SCCB) is a rare variant of bladder cancer with poor outcomes. We evaluated long-term outcomes of nonmetastatic (M0) and metastatic (M1) SCCB and correlated pathologic response with genomic alterations of patients treated with neoadjuvant chemotherapy (NAC). Patients and Methods: Clinical history and pathology samples from SCCB patients diagnosed at our institution were reviewed. Results: One hundred and ninety-nine SCCB patients were identified. (M0: 147 [74%]; M1: 52 [26%]). Among M0 patients, 108 underwent radical cystectomy (RC) (NAC: 71; RC only: 23; adjuvant chemotherapy: 14); 14 received chemoradiotherapy; the rest received chemotherapy alone or no cancer-directed therapy. RC-only patients had a median follow-up of 9.1 years, and median disease-free survival (DFS) and overall survival (OS) were 1.1 and 1.2 years, respectively. NAC patients had pathologic response (<pT2pN0) and pathologic complete response (pT0pN0) rates of 48% and 38%, respectively, with median follow-up of 7.2 years, and median DFS and OS of 5.6 and 14.5 years, respectively. NAC responders (<ypT2N0) had superior median DFS (14.5 vs. 0.6 years, hazard ratio [HR] 0.24, P< .001) and OS (14.5 vs. 2.5 years, HR 0.31, P = .002). DFS rates for responders and nonresponders were 76% and 27% at 5 years, and 71% and 23% at 10 years, respectively. Local and central nervous system recurrences were infrequent. Median progression-free survival (PFS) and OS for M1 disease were 6.9 and 10.3 months, respectively. Genomic profiling was performed on 47 NAC patients. Loss of ERCC2 function was significantly enriched among those with pathologic complete response to NAC (mutations present in 50% of pathologic complete responders vs. 15% nonresponders, P = .045). Conclusion: M0 SCCB is chemo-sensitive and patients have excellent long-term survival following response to NAC. Patients with M1 disease have poor survival despite systemic therapy. Loss-of-function mutations of ERCC2 were associated with pathologic complete response to NAC. © 2022 Elsevier Inc.
Keywords:	bladder cancer; radical cystectomy; urothelial carcinoma; neuroendocrine carcinoma; small cell bladder cancer
Journal Title:	Clinical Genitourinary Cancer
Volume:	20
Issue:	5
ISSN:	1558-7673
Publisher:	Elsevier Inc.
Date Published:	2022-10-01
Start Page:	431
End Page:	441
Language:	English
DOI:	10.1016/j.clgc.2022.05.005
PUBMED:	35676169
PROVIDER:	scopus
PMCID:	PMC9809986
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85131585913&doi=10.1016%2fj.clgc.2022.05.005&partnerID=40&md5=9d6c982f5d5eea5ae033fc65fb28ec1b
Notes:	Article -- Export Date: 3 October 2022 -- Source: Scopus