Outcomes Following Radical Cystectomy for Nested Variant of Urothelial Carcinoma: A Matched Cohort Analysis

Purpose: We evaluated oncological outcomes after radical cystectomy in patients with the nested variant of urothelial carcinoma and compared survival to that in patients with pure urothelial carcinoma of the bladder. Materials and Methods: We identified 52 patients with the nested variant who were treated with radical cystectomy between 1980 and 2004. Pathological specimens were re-reviewed by a single genitourinary pathologist. Patients were matched 1:2 by age, gender, ECOG (Eastern Cooperative Oncology Group) performance status, pathological tumor stage and nodal status to patients with pure urothelial carcinoma. Survival was estimated using the Kaplan-Meier method and compared with the log rank test. Results: Patients with the nested variant had a median age of 69.5 years (IQR 62, 74) and a median postoperative followup of 10.8 years (IQR 9.3, 11.2). Nested variant cancer was associated with a high rate of adverse pathological features since 36 patients (69%) had pT3-T4 disease and 10 (19%) had nodal invasion. Eight patients (15%) with nested variant cancer received perioperative chemotherapy. When patients with the nested variant were matched to a cohort with pure urothelial carcinoma, no significant differences were noted in 10-year local recurrence-free survival (83% vs 80%, p = 0.46) or 10-year cancer specific survival (41% vs 46%, p = 0.75). Conclusions: The nested variant of urothelial carcinoma is associated with a high rate of locally advanced disease at radical cystectomy. However, when stage matched to patients with pure urothelial carcinoma, patients with the nested variant did not have an increased rate of recurrence or adverse survival. Further studies are required to validate these findings and guide the optimal multimodal treatment approach to these patients.