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Knowledge of the comparative oncologic outcomes of histologic variants after radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) relies on small case series. We compared the effect of pure squamous cell carcinoma, adenocarcinoma, and neuroendocrine carcinoma compared with pure urothelial carcinoma (PUC) on overall survival (OS) and pathologic tumor, lymph node, and surgical margin status after RC.Using the National Cancer Database, we retrospectively examined patients undergoing RC for MIBC from 2003 to 2011. Our cohort was stratified according to histologic type and included only pure variants: squamous cell, adenocarcinoma, neuroendocrine, and PUC. Inverse probability weighting-adjusted and facility-clustered Cox and logistic regression analyses were used to assess the effect of histologic variants versus PUC on OS and pathologic outcomes.Overall, 475 (4.4%), 224 (2.1%), 155 (1.4%), and 10,033 (92.2%) patients underwent RC for MIBC with pure squamous cell carcinoma, adenocarcinoma, neuroendocrine carcinoma, and PUC, respectively. In inverse probability weighting-adjusted analyses, squamous cell (hazard ratio, 1.26; 95% confidence interval [CI], 1.07-1.49; P = .006) and neuroendocrine (hazard ratio, 1.53; 95% CI, 1.21-1.95; P < .001) types were associated with worse OS relative to PUC. Squamous cell carcinoma (odds ratio [OR], 1.58; 95% CI, 1.23-2.04; P < .001), adenocarcinoma (OR, 1.49; 95% CI, 1.04-2.14; P = .030), and neuroendocrine carcinoma (OR, 2.37; 95% CI, 1.58-3.55; P < .001) at diagnosis were associated with greater odds of ≥ pT3 disease. The squamous cell and neuroendocrine variants were associated with decreased (OR, 0.66; 95% CI, 0.48-0.91; P = .012) and increased (OR, 1.58; 95% CI, 1.06-2.37; P = .026) odds of pN+ disease, respectively. Adenocarcinoma was associated with greater odds of positive margins (OR, 2.14; 95% CI, 1.39-3.30; P = .001).Pure squamous cell and neuroendocrine carcinoma histologic types were associated with worse OS relative to PUC. However, no difference was found between adenocarcinoma and PUC. All histologic variants were associated with higher tumor stage at surgery compared with PUC.The present retrospective study evaluated the effect of nonurothelial bladder cancer variants on overall survival and pathologic tumor and lymph node status and surgical margins after radical cystectomy. After propensity score-weighting, pure squamous cell and neuroendocrine cancer, but not adenocarcinoma, were associated with worse survival compared with pure urothelial carcinoma. All variants were associated with higher tumor stage at surgery.