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Background  High-grade urothelial carcinomas (UCs) often show foci of variant differentiation. There is limited information in the literature about the response of these variant urothelial tumors to immunotherapy with bacillus Calmette–Guerin (BCG). We compared the response, to treatment with BCG, of UC containing glandular, squamous, nested, and micropapillary types of differentiation to response of conventional non-muscle invasive high-grade UC.    Methods  A total of 100 patients were diagnosed with variant histology urothelial cancer between June 1995 and December 2013. Forty-one patients with Ta or T1, confirmed by second look biopsies, received immunotherapy with BCG. Fourteen patients in this group were diagnosed with micropapillary differentiation, 13 patients with squamous differentiation, 9 patients with glandular differentiation, and 7 patients with nested variants. The control group included 140 patients with conventional high-grade UC. Both groups have been treated and followed similarly.    Findings  Patients with variant tumors had similar clinical features to patients with conventional disease, including age, male to female ratio, stage, the presence of Tis, and median follow-up. Patients with variant tumors had a significantly worse prognosis compared to patients with conventional high-grade UC, including 5-year recurrence-free survival (63.5 Vs. 71.5%,  p  = 0.05), 5-year progression (≥T2)-free survival (60 Vs. 82.5%,  p  = 0.002), 5-year disease-specific survival (73 Vs. 92.5%,  p  = 0.0004), and overall survival (66 Vs. 89.5%, 0.05).    Interpretation  A patient with variant bladder cancer treated with intravesical immunotherapy has a 27% chance of dying from this disease within 5 years compared to 7.5% chance for a patient with conventional high-grade UC.

The Response of Variant Histology Bladder Cancer to Intravesical Immunotherapy Compared to Conventional Cancer