Risk of subsequent recurrences and progression in NMIBC patients with early recurrence.

OBJECTIVE: To investigate how the timing of the first non-muscle invasive bladder cancer (NMIBC) recurrence influences the risk of subsequent recurrences and progression. Furthermore, to examine the relationship between multiple recurrences in NMIBC. METHODS: Using nationwide Danish health registers, we identified NMIBC patients diagnosed between 2009 and 2020 who experienced at least one recurrence. Patients were categorized by timing of first recurrence: early (≤12 months from primary diagnosis) or late (>12 months). We estimated cumulative incidences of subsequent recurrences and progression. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) for early versus late recurrence, adjusting for age, sex, primary T-stage, and grade. The Prentice-Williams-Peterson (PWP) Total Time model estimated the hazard of subsequent recurrences when accounting for previous recurrences. RESULTS: Among 6,886 patients with recurrence, 3,898 were early and 2,988 late. The 1-year cumulative incidence of subsequent recurrence was 47% (95% CI 45-49) for early versus 26% (95% CI 24-28) for late recurrence. Corresponding 1-year progression incidences were 10% (95% CI 9.5-11) and 4.0% (95% CI 3.4-4.8). Adjusted HRs for subsequent recurrence were 1.73 (95% CI 1.63-1.85; p<0.001) in Cox models and 1.19 (95% CI 1.12-1.25; p<0.001) in the PWP model. For progression, the adjusted HR was 1.75 (95% CI 1.55-1.98; p<0.001). CONCLUSION: Early recurrence after primary NMIBC diagnosis was associated with significantly higher risks of subsequent recurrence and progression. Timing of the first recurrence may serve as a clinically relevant prognostic marker and could influence future follow-up strategies.