Surveillance colonoscopy at 5 years after removal of high-risk adenomas was noninferior to surveillance at 3 years in terms of colorectal cancer incidence during the first 5 years after adenoma removal, according to an interim analysis of the randomized EPoS II trial reported by Jover et al in The New England Journal of Medicine.
Current guidelines recommend that patients with high-risk adenomas undergo their first surveillance colonoscopy 3 years after polyp removal. However, those recommendations are based largely on observational data and small randomized trials, and more frequent surveillance adds cost, burden, and procedural risk.
More than 99% of patients in the study remained free of a colorectal cancer diagnosis during the roughly 5 years after their high-risk adenomas were removed, regardless of whether surveillance colonoscopy began at 3 years or 5 years.
“This finding may trigger a discussion of the categorization of these patients as being at high risk for colorectal cancer,” the investigators wrote.
Study Details
The ongoing noninferiority trial enrolled 10,799 patients aged 40 to 74 years at 49 endoscopy centers in 8 European countries. High-risk adenomas were defined as at least one adenoma measuring 10 mm or larger, high-grade dysplasia or villous growth, or 3 to 10 adenomas of any kind.
Patients were randomly assigned to have their first surveillance colonoscopy either 3 or 5 years after adenoma removal; those in the 3-year group also underwent another colonoscopy at 5 years. The primary endpoint for the full trial is cumulative colorectal cancer incidence at 10 years; the current report is an interim analysis after 5.5 years of follow-up.
Key Findings
The 5-year cumulative incidence of colorectal cancer was 0.77% with surveillance beginning at 5 years and 0.82% with surveillance beginning at 3 years, meeting the trial’s prespecified criterion for noninferiority. Among the relatively few colorectal cancers that occurred, stage distribution was similar between the two groups. Colorectal cancer deaths were also uncommon, occurring in three patients (0.06%) in the 5-year group and two (0.04%) in the 3-year group.
Patients assigned to begin surveillance at 5 years underwent 48.5% fewer colonoscopies during follow-up, with 4,434 procedures compared with 8,614 in the 3-year group. More frequent surveillance was also associated with greater adenoma detection. In the weighted analysis, advanced adenomas were found in 14.55% of patients in the 3-year group vs 11.07% in the 5-year group, while adenomas of any kind were detected in 71.77% vs 54.82%, respectively. The investigators suggested that the difference likely reflected the additional opportunity to detect adenomas during a second surveillance colonoscopy in the 3-year group, including lesions that may have been missed previously.
“Whether the higher level of detection is beneficial for patients remains to be seen,” the investigators wrote.
The authors offered two reasons the added detection may not translate into patient benefit. First, the between-group difference in advanced adenomas was small, and even advanced adenomas grow slowly, meaning lesions missed until the 10-year colonoscopy may still be found before malignant transformation. Second, observational data suggest that adenoma detection beyond roughly 25% to 30% may add little protection against colorectal cancer, and adenomas were found in more than 50% of patients in each group, a level the authors suggest may be sufficient. The 10-year analysis may provide further insight.
They cautioned that this is an interim analysis of a 10-year trial and that the criterion for noninferiority was met narrowly. In addition, only about 70% of patients in the 5-year group and 65% in the 3-year group completed the planned 5-year surveillance colonoscopy.
“The results of our trial may encourage updates to the recommendations for surveillance intervals,” the investigators wrote.
Rodrigo Jover, MD, PhD, of Servicio de Medicina Digestiva, Hospital General Universitario Dr. Balmis in Alicante, Spain, and Michael Bretthauer, MD, PhD, of the Clinical Effectiveness Research Group at the University of Oslo, are corresponding authors of the study.
DISCLOSURE: The study was supported by the Research Council of Norway and additional research grants from organizations in the participating countries. The funders had no role in trial design or conduct, data collection or analysis, or preparation of the manuscript. For full disclosures of the study authors, visit nejm.org.
