Published September 16, 2026
N Engl J Med 2026;395:1051-1061
DOI: 10.1056/NEJMoa2603816
Abstract
Background
More evidence is needed to inform recommendations for intervals of colonoscopy surveillance after polyp removal.
Methods
In this ongoing noninferiority trial conducted in eight European countries, we randomly assigned patients with high-risk adenomas (defined as ≥1 adenoma with a diameter of ≥10 mm, high-grade dysplasia, or villous growth or 3 to 10 adenomas of any kind) to undergo a first colonoscopy at 5 years after polyp removal or at 3 years; surveillance at 3 years is currently recommended in guidelines. The 3-year group also underwent colonoscopy at 5 years. The primary end point is the cumulative incidence of colorectal cancer at 10 years, with a prespecified noninferiority margin of 0.7 percentage points for the upper boundary of the confidence interval for the difference between the two groups. Here, we report the results of an interim analysis conducted after 5.5 years of follow-up. Inverse probability weighting was used to account for missing data owing to nonparticipation in surveillance colonoscopy at 5 years. In this analysis, the incidence of colorectal cancer is reported with a one-sided 99.12% confidence interval; for the final analysis at 10 years, the plan is to calculate a 95.33% confidence interval to maintain an overall type I error of 5%.
Results
A total of 10,799 patients underwent randomization: 5398 patients were assigned to the 5-year group and 5401 to the 3-year group. The 5-year cumulative incidence of colorectal cancer was 0.77% with less-frequent surveillance and 0.82% with more-frequent surveillance (difference, −0.05 percentage points); the upper boundary of the 99.12% confidence interval was 0.68, which met the criterion for noninferiority. The distribution of cancer stage at diagnosis did not appear to differ substantially between the two groups. A total of 5 patients died of colorectal cancer: 3 patients (0.06%) in the 5-year group and 2 (0.04%) in the 3-year group.
Conclusions
In this interim analysis of a 10-year noninferiority trial, beginning surveillance colonoscopy at 5 years after polyp removal was noninferior to beginning at 3 years with respect to the cumulative incidence of colorectal cancer at 5 years among patients with high-risk adenomas. (Funded by the Research Council of Norway and others; EPoS II ClinicalTrials.gov number, NCT02319928.)
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Notes
A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
Supported by grants (235271 and 315410) from the Research Council of Norway, a grant from the Kristian Gerhard Jebsen Foundation to the K.G. Jebsen Center for Colorectal Cancer Research, grants (PI14/01386, PI17/01756, PI20/01527, and PI23/01974) from the Instituto de Salud Carlos III, grants (Beca Gonzalo Miño 2014 and 2020) from the Asociación Española de Gastroenterología, a grant (Beca 2018) from the Sociedad Española de Endoscopia Digestiva, a grant (2019/34/H/NZ5/00743) from the National Science Center, a grant (10274) from the Koningin Wilhelmina Fonds Kankerbestrijding–Dutch Cancer Society, and a grant (R167-A11048) from the Danish Cancer Society.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
We thank the EPoS trial coordinators Madeleine Skotnes (current) and Anita Aalby (past) at the University of Oslo, without whom this project would not have been possible.
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History
Published online: September 16, 2026
Published in issue: September 17, 2026
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Cited by
- When More Is Not Better — Colonoscopy Surveillance after High-Risk Adenomas, New England Journal of Medicine, 395, 11, (1123-1124), (2026)./doi/full/10.1056/NEJMe2608876
- Colorectal Cancer Risk among Patients with Serrated Polyps, New England Journal of Medicine, 395, 11, (1134-1135), (2026)./doi/full/10.1056/NEJMc2605026
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