Recurrence patterns in patients with low-grade intermediate-risk non-muscle invasive bladder cancer eligible for active surveillance

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. Methods We retrospectively evaluated 174 LG IR-NMIBC patients who underwent transurethral resection of bladder tumor (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 ≤ 1cm). 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 TaLG disease. After a median follow-up of 36 months (IQR 20–54), 75 (43%) and 32 (18%) patients experienced any- and HG recurrence, respectively. The 3-year 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%) of 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 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.