Risk stratification of Ta high-grade non-muscle-invasive bladder cancer: Insights from a multicenter cohort study.

BACKGROUND AND

OBJECTIVE

The oncological risk of patients with Ta high-grade (TaHG) non-muscle-invasive bladder cancer (NMIBC) remains uncertain. We aimed to evaluate the oncological outcomes of TaHG patients treated with Bacillus Calmette-Guérin (BCG) by applying the 2021 European Association of Urology (EAU) and the American Association of Urology (AUA) risk stratifications and assessing the prognostic value of individual risk factors.

METHODS

We identified 529 TaHG patients without carcinoma in situ (CIS) treated with BCG from 16 tertiary centers between 2003 and 2024. BCG failure was defined as the development of BCG-unresponsive status, BCG relapsing status or identification of muscle invasive bladder cancer during follow-up. TaHG patients were stratified according to the number of EAU and AUA risk factors in three groups (0, 1, 2-3 risk factors), and in intermediate risk (IR-TaHG) and high-risk (HR-TaHG) according to both EAU and AUA risk stratifications. Cumulative incidence analyses and Cox regression models analyzed the 5-yr risk of HG-recurrence, progression and BCG failure among TaHG patients stratified according to the number of EAU and AUA risk factors.

KEY FINDINGS: At a median follow-up of 40 months (IQR: 37-42), 114 (22%) TaHG patients experienced a HG-recurrence, 49 (9%) patients had progression and 107 (20%) had BCG failure. No differences in the risk of HG-recurrence, progression and rates of BCG failure were detected in TaHG patients stratified according to the number of EAU or AUA risk factors (all P < 0.05). No differences in the risk of 5-year HG-recurrence were observed between IR-TaHG and HR-TaHG patients according to both EAU (26% vs. 31%, P = 0.10) and AUA risk stratifications (24% vs. 29%, P = 0.07). Similarly, no differences in the 5-yr risk of progression were detected among IR-TaHG and HR-TaHG according to EAU (13% vs. 15%, P = 0.3) and AUA risk stratifications (12% vs. 15%, P = 0.2). No differences in the risk of BCG failure were observed between IR-TaHG and HR-TaHG according to both EAU and AUA risk stratifications (all P > 0.05).

CONCLUSION AND CLINICAL IMPLICATIONS: We observed no differences in HG-recurrence, progression, or BCG failure rates among patients with TaHG NMIBC, regardless of the number of EAU or AUA risk factors harbored. These findings may speculatively support the increasing need for BCG-adapted risk stratification and the consideration of all TaHG tumors without CIS as a homogenous population with a similar oncological risk, regardless of individual risk factors.