Multi-institutional external validation of the European risk classification for high-grade Ta non-muscle-invasive bladder cancer

Abstract

Purpose: Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease, with Ta tumors accounting for about 70% of cases. Prognosis varies widely, especially among high-grade (HG) tumors, and current predictive systems remain imperfect. This study aimed to provide an external validation of the EAU 2021 classification for Ta HG tumors.

Methods: A retrospective European multicenter study was conducted in 316 TaHG NMIBC. According to the presence or absence of risk factors (age > 70 years, multifocality, tumor size > 3 cm), we categorized TaHG between intermediate-risk (IR) and high-risk (HR) NMIBC. Oncological outcomes included overall and HG recurrence-free survival (RFS), progression free-survival (PFS), cystectomy free-survival (CFS), cancer specific survival (CSS) and overall survival (OS). Uni- and multivariable Cox regression analyses were used to identify the independent predictors of disease recurrence and progression.

Results: Overall, 197 (62%) and 119 (38%) patients had IR and HR HG Ta NMIBC, respectively. All patients received endovesical instillations (BCG or chemotherapy). After a median follow-up of 36.0 [32.0; 42.0] months, IR was significantly associated with a higher 3-yr overall RFS (78.6% vs. 66.5%; p = 0.01), 3-yr HG RFS (79.9% vs. 69.2%; p = 0.03) and 3-yr PFS (97.2% vs. 91.5%; p = 0.02). CFS, CSS and OS were similar between IR and HR (all p > 0.05). Multivariable Cox regression analysis confirmed that HR vs. IR group was significantly associated with overall disease recurrence (HR = 1.69; p = 0.03), HG disease recurrence; (HR = 1.58; p = 0.04) and disease progression (HR = 2.33; p = 0.05).

Conclusion: The European classification of TaHG NMIBC offers useful prognostic insight, especially concerning disease recurrence and progression.

Keywords: Bladder cancer; High-grade; Non-muscle invasive; Progression; Recurrence; Stage Ta.