Updated European Association of Urology (EAU) Prognostic Factor Risk Groups Overestimate the Risk of Progression in Patients with Non-muscle-invasive Bladder Cancer Treated with Bacillus Calmette-Guérin - Beyond the Abstract

Non-muscle invasive bladder cancer (NMIBC) represents a heterogeneous group of patients with varying risks of recurrence and progression. Accurate risk stratification of patients is therefore crucial in establishing treatment recommendations.

The European Association of Urology (EAU) Guidelines Panel recently published updated prognostic factor risk groups incorporating both WHO 2004/2016 and WHO 1973 classification systems (Sylvester 2021). This scoring model is available as an online calculator (https://nmibc.net) and provides an individual’s probability of progression to muscle-invasive bladder cancer (MIBC) at 1-, 5- and 10-years. In addition to the existing ‘low’, ‘intermediate’ and ‘high’ risk groups, a new ‘very high’ risk group was created to identify patients at highest risk of progression to MIBC who might benefit most from immediate radical cystectomy. However, these new risk group definitions were derived from datasets excluding patients treated with bacillus Calmette-Guerin (BCG).

Our study, therefore, sought to determine the validity of the 2021 EAU prognostic factor risk groups in patients treated with BCG. We analyzed patients treated with BCG at our institution between 2000 and 2018 according to receipt of ‘at least induction’ and ‘adequate’ BCG (defined by the EAU and US Food & Drug Administration as ‘at least 5 of 6 induction doses plus 2 out 3 maintenance doses or 2 out of 6 doses of a second induction course’). Kaplan-Meier methods were used to estimate the risks of progression at 1- and 5- years and these risks were compared to those provided by the updated EAU prognostic factor risk groups.

We found that the updated EAU prognostic factor risk groups were able to successfully stratify progression risks in our cohort. However, the risk of progression was overestimated in the ‘very high’ risk group in both ‘at least induction’ (6.9% vs. 16.0% at 1 yr; 16.7% vs. 40.0% at 5 yr) and ‘adequate’ BCG (4.0% vs. 16% at 1 yr; 14.9% vs. 40.0% at 5 yr) cohorts, with the greatest difference in risk observed at 5 years.

These results should not come as a surprise. Indeed, the CUETO group reported similar findings when validating the EORTC risk tables in BCG-treated patients. Moreover, we now know that excellent outcomes may be achieved with BCG in contemporary practice that employs advanced cystoscopic techniques, re-TURBT and maintenance BCG (Matulay 2021). Clearly, there are a proportion of patients in the ‘very high’ risk group that will derive great benefit from BCG and in whom radical cystectomy represents overtreatment. We must therefore be cautious about recommending radical cystectomy as standard of care for all patients that fall into this risk group.

Identification of patients who may be spared surgery is ultimately key given the high morbidity and mortality of cystectomy and underscores the urgent need for predictive biomarkers. Until such biomarkers become available, we suggest these findings be used in conjunction with the updated EAU prognostic factor risk groups to counsel patients about their risk of progression to MIBC with and without BCG.

Written by: Niyati Lobo, FRCS (Urol), 2020-2021 Urology Foundation Fulbright Scholar and Ashish Kamat, MD, The University of Texas MD Anderson Cancer Center

References:

  1. Sylvester RJ, Rodríguez O, Hernández V, et al. European Association of Urology (EAU) Prognostic Factor Risk Groups for Non–muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel. European Urology. 2021;79(4):480-488.
  2. Fernandez-Gomez J, Madero R, Solsona E, et al. The EORTC tables overestimate the risk of recurrence and progression in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin: external validation of the EORTC risk tables. Eur Urol 2011; 60:423-30.
  3. Matulay JT, Li R, Hensley P, et al. Contemporary outcomes of patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin: implications for clinical trial design. J Urol 2021;205:1.

Read the Abstract
email news signup