Endoscopic Surveillance in Serrated Polyposis Syndrome, Two or Three-Year Intervals: A Non-inferiority Randomized Trial

BACKGROUND: Serrated polyposis syndrome, the most prevalent colonic polyposis, confers an increased colorectal cancer risk. Guidelines recommend close colonoscopy surveillance, but recent data suggest low neoplasia rates, supporting longer colonoscopy intervals. AIMS: Compare advanced neoplasia incidence between two- and three-year surveillance. METHODS: A multicentre, randomized non-inferiority trial was conducted (May 2021-November 2024) in six Spanish hospitals. Patients fulfilling the 2019 WHO criteria for serrated polyposis syndrome, including newly diagnosed individuals and those already under surveillance, with no advanced neoplasia and fewer than five relevant polyps at their previous colonoscopy, were randomized to surveillance at 2 or 3 years. The primary endpoint was advanced neoplasia incidence. RESULTS: A total of 131 patients with serrated polyposis syndrome were included (47.3% women; mean age 66.1). Seventy-two were assigned to 2-year and 59 to 3-year colonoscopy. Among 771 resected lesions, 2.4% were advanced adenomas or advanced serrated polyps; no colorectal cancer was detected. The proportion of patients with advanced neoplasia in the surveillance colonoscopy was 6.9% (2-year) vs 13.6% (3-year), with no statistical difference (p = 0.208) but with a risk difference of + 6.7% (95% CI -4.1 to 17.5%) exceeding the pre-specified non-inferiority margin of + 10%. Time since serrated polyposis syndrome diagnosis ≤ 3 years was associated with advanced neoplasia (OR 4.4; 95% CI 1.56-14.71; p = 0.024). CONCLUSIONS: In patients with serrated polyposis syndrome, extending colonoscopy surveillance to a three-year compared with a two-year interval yielded inconclusive evidence regarding non-inferiority for advanced neoplasia incidence. The early years following serrated polyposis syndrome diagnosis were identified as a risk factor for advanced neoplasia. TRIAL REGISTRATION: Clinical Trial Registry ClinicalTrials.gov (NCT04906343). Date: 5-10-2021.