The impact of time-to-recurrence on post-recurrence mortality in stage I-III colorectal cancer: A nationwide Danish cohort study.

Recurrence is a major risk factor of death following treatment for colorectal cancer (CRC). Postoperative surveillance aims to diagnose recurrence early to improve chances of cure. However, early recurrences may represent aggressive tumors associated with poor prognosis. This study investigated the association between time-to-recurrence and post-recurrence mortality in a nationwide cohort of 34,166 patients undergoing curative surgery for UICC stages I-III CRC in Denmark during 2004-2019 among which we identified 7027 recurrence patients by applying a validated recurrence detection algorithm to nationwide health registry data. Patients were followed from recurrence and until death or January 1st 2023. The time from surgery to recurrence was fitted with a restricted spline in a Cox proportional hazards model adjusted for sex, age, comorbidities, and location and pathological TNM stage of the primary CRC tumor. A total of 4025 recurrence patients died within 5 years after recurrence with 80% registered as a CRC-related cause of death. Median post-recurrence survival was 38.2 months (95% CI: 36.1-40.1 months). Relative to recurrences diagnosed at postoperative year 3 (reference), the 5-year post-recurrence CRC-specific HR was 1.36 (95% CI: 1.28-1.44) for recurrences diagnosed at 1 year, decreasing to HR = 0.67 (95% CI: 0.56-0.82) for recurrences diagnosed at year 5. In stratified analyses most recurrence sites followed this pattern, though not local and liver-only recurrences. This study suggests that time from surgery to recurrence diagnosis is prognostic of post-recurrence mortality after curative surgery for non-metastatic CRC. Early identification of recurrent tumors in the first postoperative years is of immense importance.