Clinical Outcomes and Malignant Potential of Urothelial Atypia Without Previous Bladder Cancer

BACKGROUND: Flat urothelial lesions, including reactive urothelial atypia (RUA) and atypia of unknown significance (AUS), represent diagnostic categories with differing implications; although RUA is a benign reactive process, AUS retains unclear malignant potential. OBJECTIVE: In this study, we aimed to evaluate the clinical characteristics and risk of bladder cancer (BCa) development in a contemporary cohort of patients with urothelial atypia without previous malignancy. DESIGN, SETTING AND PARTICIPANTS: We conducted a bicentric retrospective study of patients with RUA and AUS between 2005 and 2025 at two tertiary institutions. Patients with previous or concurrent BCa were excluded. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the development of BCa. Median follow up was calculated using the reverse Kaplan-Meier method. All statistical analysis were conducted using Python (version 3.10.12) and a p <0.05 was considered statistically significant. RESULTS AND LIMITATIONS: A total of 103 patients were included (59 RUA and 44 AUS) with a median follow-up of 4.8 yr. Overall development of BCa was uncommon, with five events observed (three RUA and two AUS) and 5-yr probabilities of 2.2% and 6.5%, respectively. Among progressors, both AUS cases developed high-grade disease. CONCLUSIONS: Patients with de novo RUA and AUS have a low but non-negligible risk of BCa. Although overall outcomes were similar between subtypes, AUS demonstrated a higher 5-yr incidence of progression and earlier development of high-grade disease among those who progressed. These findings suggest that subsequent BCa in patients with flat urothelial atypia short of carcinoma in situ may reflect an underlying urothelial process or field effect rather than the malignant potential of the atypia itself, supporting a structured, risk-adapted approach rather than routine discharge after diagnosis.