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

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.

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.

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).

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.