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Purpose: Small cell carcinoma of the bladder (SCCB) is rare, accounting for less than 1% of all bladder carcinomas. It is aggressive, and outcomes are poor as a result of its early metastatic spread. Owing to its rarity, there are limitations on data to propose standardized management pathways.Methods and Materials: We conducted a retrospective analysis of patients presenting with pure or predominant-histology SCCB to 26 institutions in the United Kingdom between 2006 and 2016. The data cutoff date was February 1, 2018. We report patient characteristics, treatment received, and subsequent clinical outcomes.Results: A total of 409 eligible patients were included. Among these, 306 (74.8%) were male, the median age was 71 years (range, 35-96 years), and 189 patients (46.2%) had pure-histology SCCB. At data cutoff, 301 patients (73.6%) had died. The median overall survival (OS) was 15.9 months (95% CI, 13.2-18.7 months). Two hundred patients (48.9%) were confirmed to have bladder-confined disease (N0, M0), with a median OS of 28.3 months (95% CI, 20.9-35.8 months), versus a median OS of 12.7 months (95% CI, 10.9-14.6 months) for the 172 patients (42.1%) with confirmed N1-3 and/or M1 disease (hazard ratio [HR], 2.03; 95% CI, 1.58-2.60; P < .001). A total of 247 patients (61.5%) received primary chemotherapy, with a median OS of 21.6 months (95% CI, 15.5-27.6 months), versus a median OS of 9.1 months (95% CI, 5.4-12.8 months) in patients who did not receive primary chemotherapy (HR, 0.46; 95% CI, 0.37-0.59; P < .001). Choice of chemotherapy agent did not alter outcomes. For those with bladder-confined disease, 61 (30.5%) underwent cystectomy, and 104 (52.0%) received radiation therapy. Survival outcomes were similar for both cystectomy and radiation therapy. Only 6 patients (1.5%) were identified as having brain metastases at any time point.Conclusions: To our knowledge, this is the largest retrospective study of all-stage SCCB to date. Patients have a poor prognosis overall, but survival is improved in those able to receive chemotherapy and with organ-confined disease. Brain metastases are rare. [ABSTRACT FROM AUTHOR]

Organ-confined muscle-invasive bladder cancer is treated with cystectomy or bladder preservation techniques, including radiation therapy. There are currently no biomarkers to inform management decisions and aid patient choice. Previously we showed high levels of MRE11 protein, assessed by immunohistochemistry (IHC), predicted outcome after radiation therapy, but not cystectomy. Therefore, we sought to develop the MRE11 IHC assay for clinical use and define its relationship to clinical outcome in samples from 2 major clinical trials. Samples from the BCON and BC2001 randomized controlled trials and a cystectomy cohort were stained using automated IHC methods and scored for MRE11 in 3 centers in the United Kingdom. Despite step-wise creation of scoring cards and standard operating procedures for staining and interpretation, there was poor intercenter scoring agreement (kappa, 0.32; 95% confidence interval, 0.17-0.47). No significant associations between MRE11 scores and cause-specific survival were identified in BCON (n = 132) and BC2001 (n = 221) samples. Reoptimized staining improved agreement between scores from BCON tissue microarrays (n = 116), but MRE11 expression was not prognostic for cause-specific survival. Manual IHC scoring of MRE11 was not validated as a reproducible biomarker of radiation-based bladder preservation success. There is a need for automated quantitative methods or a reassessment of how DNA-damage response relates to clinical outcomes. [ABSTRACT FROM AUTHOR]