Five-Year Colonoscopy Surveillance Noninferior at Interim Analysis

Beginning surveillance colonoscopy 5 years after high-risk adenoma removal was noninferior to beginning at 3 years for the 5-year cumulative incidence of colorectal cancer, according to an interim analysis of a randomized trial published in NEJM.

The ongoing EPoS II noninferiority trial included patients from 8 European countries. High-risk adenomas were defined as at least 1 adenoma measuring 10mm or larger, an adenoma with high-grade dysplasia or villous growth, or 3 to 10 adenomas of any type. Investigators randomly assigned 10,799 patients to first surveillance at 5 years or at 3 years, the interval currently recommended in guidelines. The 3-year group also underwent colonoscopy at 5 years.

The trial’s primary endpoint is the cumulative incidence of colorectal cancer at 10 years. Investigators prespecified a noninferiority margin of 0.7 percentage points for the upper confidence-interval boundary. The interim analysis was conducted after 5.5 years of follow-up and used inverse probability weighting to account for missing data related to nonparticipation in the 5-year surveillance colonoscopy.

Among 5398 patients assigned to the 5-year group and 5401 assigned to the 3-year group, the 5-year cumulative incidence of colorectal cancer was 0.77% and 0.82%, respectively. The between-group difference was −0.05 percentage points, and the upper boundary of the one-sided 99.12% confidence interval was 0.68 percentage points, meeting the prespecified noninferiority criterion. Cancer stage at diagnosis did not appear to differ substantially between groups.

Five patients died of colorectal cancer: 3 patients (0.06%) in the 5-year group and 2 (0.04%) in the 3-year group. The investigators concluded that starting surveillance at 5 years was noninferior to starting at 3 years at this interim assessment. The trial remains ongoing, with its primary analysis planned at 10 years.

Source: Jover R, Bretthauer M, Cubiella J, et al. Colonoscopy intervals and colorectal cancer incidence after adenoma removal. N Engl J Med. 2026;395(11):1051-1061. doi:10.1056/NEJMoa2603816