Rodrigo Jover, Michael Bretthauer, Joaquin Cubiella, Sarah J E Barry, Anna Macios, Lauren Barnett, Rune Erichsen, Michal F Kaminski, Hans-Olov Adami, Øyvind Holme, Joep Ijspeert, Monika Ferlitsch, Mario Dinis-Ribeiro, Maria Pellise, Alejandro Martínez-Roca, Sandra Baile-Maxía, Luisa de-Castro, Luis Bujanda, Pilar Díez-Redondo, Jens Aksel Nordberg Nilsen, Hong Dung Nguyen, Linn Bernklev, Jørgen Tilma, Uffe Schou Løve, Claudia Jaensch, Nastazja D Pilonis, Mirosław Szura, Andrzej Bialek, Annemarie van Berkel, Manon C W Spaander, Frank Ter Borg, Monique E van Leerdam, Miguel A Hernán, Jaroslaw Regula, Magnus Løberg, Evelien Dekker, Mette Kalager, EPoS Study Group
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.).
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.).