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.