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).
Clinical history and pathology samples from SCCB patients diagnosed at our institution were reviewed.
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).
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.
Clinical genitourinary cancer. 2022 May 11 [Epub ahead of print]
Min Yuen Teo, Brendan J Guercio, Arshi Arora, Xueli Hao, Ashley M Regazzi, Timothy Donahue, Harry W Herr, Alvin C Goh, Eugene K Cha, Eugene Pietzak, Sherri M Donat, Guido Dalbagni, Bernard H Bochner, Semra Olgac, Judy Sarungbam, S Joseph Sirintrapun, Ying-Bei Chen, Anuradha Gopalan, Samson W Fine, Satish K Tickoo, Victor E Reuter, Britta Weigelt, Anne M Schultheis, Samuel A Funt, Dean F Bajorin, David B Solit, Gopa Iyer, Irina Ostrovnaya, Jonathan E Rosenberg, Hikmat Al-Ahmadie
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address: ., Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY., Dept of Pathology, Mercy Hospital, St. Louis, MO., Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Pathology and Laboratory Medicine, Virginia Mason Medical Center, Seattle, WA., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY; Institute of Pathology, University Hospital Cologne and University of Cologne, Cologne, Germany., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY., Weill Cornell Medical College, New York, NY; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY; Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address: .