Identifying optimal candidates for active surveillance in low-grade intermediate-risk non-muscle invasive bladder cancer.

Objective: The intermediate-risk non-muscle invasive bladder cancer (IR-NMIBC) prognostic group is heterogeneous. Growing evidence supports the role of active surveillance (AS) for patients with low-risk NMIBC, however, no clear data exists considering IR-NMIBC. The aim of the study was to assess the risk of recurrence of patients eligible for AS based on the International Bladder Cancer Group (IBCG) stratification.

Methods: We retrospectively evaluated 174 LG IR-NMIBC patients who underwent transurethral resection of bladder tumor (index TURBT) from 2012 to 2023 at a tertiary referral center and fulfilled the inclusion criteria for enrollment in AS protocols at the index TURBT (≤ 5 suspicious lesions, no macrohematuria, negative urine cytology, lesions ≤ 1 cm). Patients were then stratified according to the International Bladder Cancer Group (IBCG) risk factors: frequent recurrence, early recurrence, previous instillation, and multifocality. Kaplan Meier plots and multivariable Cox regression analysis (MVA) were used to assess the risk of any and high-grade (HG) recurrence according to the number of risk factors.

Results: Overall, 168 (97%) patients had a Ta low grade bladder tumor. After a median follow-up of 36 months [Interquartile range (IQR) 20-54], 75 (43%) and 32 (18%) patients experienced any- and HG recurrence, respectively. The 3-year recurrence free-survival (RFS) was 86% [95% Confidence Interval (CI) 76-98%] for patients with 0, 76% (95% CI 68-84%) for those with 1-2, and 54% (95% CI 34-84%) for those with ≥ 3 risk factors. The 3-year HG-RFS was > 90% for patients with 0 and 1-2 risk factors, compared to 76% (95% CI 58-99%) for those with ≥ 3 risk factors. At MVA, the presence of ≥ 3 risk factors was associated with a higher risk of recurrence [hazard ratio: 4.74, 95% CI 1.75-12.8, p = 0.002].

Conclusion: Among patients with LG IR-NMIBC eligible for AS, those with more than 2 IBCG risk factors may not be suitable candidates due to a higher risk of developing HG recurrence. Randomized controlled trials with standardized AS protocols are necessary to validate these findings and optimize patient selection for AS in LG IR-NMIBC.