The impact of squamous and glandular differentiation on survival after radical cystectomy for urothelial carcinoma

Purpose: We investigated the clinicopathological outcomes of patients treated with cystectomy for pure urothelial carcinoma vs urothelial carcinoma, and squamous and/or glandular differentiation. Materials and Methods: We reviewed the records of 1,013 patients who underwent radical cystectomy, including 827 (72%) with pure urothelial carcinoma and 186 (18%) with urothelial carcinoma, and squamous and/or glandular differentiation. Of patients with variant histology 132 had squamous differentiation, 41 had glandular features and 13 had each type. Cancer specific survival was estimated using the Kaplan-Meier method. The association of histological differentiation with death from bladder cancer was evaluated using multivariate Cox proportional hazard regression analysis. Results: Patients with urothelial carcinoma, and squamous and/or glandular differentiation were more likely to have pT3-T4 tumors (70% vs 38%, p <0.0001) and pN+ disease (20% vs 15%, p = 0.05) than those with pure urothelial carcinoma. Median followup was 11.4 years. A total of 432 patients died of bladder cancer, including 77 with histological differentiation and 355 with pure urothelial carcinoma. Ten-year cancer specific survival did not significantly differ between patients with urothelial carcinoma and histological differentiation, and those with pure urothelial carcinoma (52% vs 51%, p = 0.71). After adjusting for clinicopathological features squamous and/or glandular differentiation was not significantly associated with the risk of death from bladder cancer (HR 0.79, p = 0.10). Conclusions: Patients with urothelial carcinoma, and squamous and/or glandular differentiation were more likely to have extravesical tumors and node positive disease. Nevertheless, they did not have adverse survival compared to patients with pure urothelial carcinoma. Additional studies are needed to further define prognostic factors in such patients.