The Prognostic Impact of Histopathological Variants in Patients with Advanced Urothelial Carcinoma

Purpose: This study investigated the prognostic role of histopathological variants in patients with advanced urothelial carcinoma (UC) who were treated with systemic chemotherapy. Materials and Methods: We conducted a retrospective analysis of patients with unresectable and/or metastatic UC who underwent systemic chemotherapy between January 1997 and December 2013 in Kaohsiung Chang Gung Memorial Hospital. Histopathological types were categorized as pure UC (PUC) and variants of UC (VUC). The overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan–Meier analyses and Cox proportional regression models. Results: A total of 206 patients were enrolled; 53 of the patients (25.7%) had histopathological variants. The most common variant was squamous differentiation (68%). Compared with patients with PUC, patients with VUC significantly exhibited upper urinary tract origin (75% vs 52%, P = .008), chronic renal insufficiency (40% vs 23%, P = .03), and carboplatin-based chemotherapy (28% vs 10%, P = .003). According to univariate analysis, the median OS for PUC patients was significantly higher than that for VUC patients (15.9 vs 11.3 months, P = .007). The median PFS for patients who received first-line chemotherapy was 6.1 and 3.8 months for PUC patients and VUC patients, respectively (P = .004). Multivariate analysis revealed that VUC (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.16–2.40, P = .006), an age ≤ 60 years (HR 0.70, 95% CI 0.49–0.99, P = .045) and presence of visceral metastasis (HR 1.54, 95% CI 1.11–2.13, P = .009) were independent factors facilitating OS prediction. Conclusions: The presence of histopathological variants indicates poor survival outcomes in patients with metastatic UC. Accordingly, VUC should be integrated into and considered an independent factor in a predictive model of survival.