Long‐term outcomes following a 5‐year recurrence‐free interval in non‐muscle‐invasive bladder cancer

OBJECTIVE: To describe the recurrence and progression trends of non-muscle-invasive bladder cancer (NMIBC) during a 14-year period in Denmark between 2009 and 2022. Furthermore, to evaluate the risk of late recurrence with or without progression in patients who initially experience a 5-year recurrence-free interval (RFI). PATIENTS AND METHODS: We conducted a nationwide cohort study of all patients diagnosed with NMIBC in Denmark between 2009 and 2022, linking data from population-based registries (N = 21 037). Recurrence was defined as a new bladder tumour ≥90 days after transurethral resection of bladder tumour, and progression followed the criteria set out by Lamm et al. or cystectomy. Cumulative incidence and Cox regression analyses described risks of recurrence and progression within 5 years after primary diagnosis. A landmark analysis assessed late recurrences with or without progression among patients who were recurrence-free for ≥5 years. RESULTS: We identified 21 037 patients with NMIBC (median age 72 years; 76% male). The 1- and 5-year cumulative incidence of recurrence was 24% (95% confidence interval [CI] 24-25%) and 44% (95% CI 43-45%), while progression risks were 4.4% (95% CI 4.1-4.7%) and 10% (95% CI 9.7-11%). Among the 6583 patients who were recurrence-free for 5 years, the subsequent 5-year cumulative incidence was 9.8% (95% CI 9.0-11%) for recurrence and 1.5% (95% CI 1.2-1.9%) for progression, with one-third progressing to MIBC. CONCLUSION: Our study confirmed previous findings that most recurrences in patients with NMIBC occur within the first years after primary diagnosis. Furthermore, we found improved recurrence-free rates over the past 14 years. Our analysis suggests the risk of recurrence and progression persists after a 5-year RFI; however, only in a limited proportion of patients. Future studies should identify specific risk factors able to predict patients' long-term risk, to tailor potential long-term follow-up schemes for patients with NMIBC.