Clinical Outcomes of Patients With Variant Histology of Urothelial Carcinoma After Radical Cystectomy

Purpose: The efficacy of standard chemotherapy or radical cystectomy in patients who have urothelial tumors with variant histology (VH) is very limited in terms of their prognosis. This study aimed to investigate the prognosis of bladder cancer (BC) patients with VH who underwent radical cystectomy (RC).Materials and Methods: We retrospectively evaluated 327 BC patients who underwent RC at Pusan National University Yangsan Hospital between February 2010 and June 2021. VH was categorized into less and more aggressive types according to the patient’s mortality risk relative to pure urothelial carcinoma (PUC). More aggressive types included micropapillary, plasmacytoid, and sarcomatoid variants. Less aggressive types comprised other variant types, including squamous differentiation, glandular differentiation, lipoid, and nested. Small cell carcinoma, pure adenocarcinoma, pure squamous cell carcinoma, and lymphoma BC were excluded from analysis. The progression-free survival (PFS) and overall survival (OS) rates were evaluated using Kaplan-Meier analysis and Cox regression.Results: After the exclusion of nonurothelial tumors, data from 299 patients were available for analysis. We identified 244 (74.6%) and 55 patients (16.8%) with PUC and urothelial carcinoma with VH, respectively. VH patients were categorized as having less aggressive (n=35) and more aggressive (n=20) types. Univariate analysis identified significant differences in PFS (p=0.031) between patients with PUC (n=244) and more aggressive VH (n=20). Multivariate analysis showed that more aggressive VH was significantly associated with OS and PFS. In the Kaplan-Meier analysis, a statistically significant difference was observed between PUC and more aggressive VH in OS and PFS.Conclusions: VH patients with more aggressive types showed more advanced TNM stages at presentation than PUC patients. Pathological upstaging after RC was more common in VH patients. Among VH patients, the presence of a more aggressive VH type can be an independent predictor of progression after RC, with a worse prognosis than that of PUC patients.