Background and study aims: Endoscopic screening with polypectomy reduces colorectal cancer (CRC) incidence. Incomplete polyp removal may attenuate the effect of screening. This randomized trial compared cold snare polypectomy (CSP) with hot snare polypectomy (HSP) regarding complete polyp resection. Patients and methods: We included patients ≥ 40 years at 8 hospitals in 4 countries who had at least one 4-9 mm non-pedunculated polyp detected at colonoscopy. Patients were randomized 1:1 to CSP or HSP. Biopsies from the resection margins were obtained systematically after polypectomy in both groups. We hypothesized that CSP would be non-inferior to HSP with a non-inferiority margin of 5%. Logistic regression models were fitted to identify factors explaining incomplete resection. Results: In total, 425 patients, with 608 polyps were randomized to either CSP or HSP. Of 318 polyps removed by CSP and 283 polyps removed by HSP, 34 (10.7%) and 21 (7.4%) were incompletely resected, respectively, with an adjusted risk difference of 3.2% (95% CI -1.4 – 7.8). There was no difference between the groups in terms of post-polypectomy bleeding, perforation, or abdominal pain. Independent risk factors for incomplete removal were serrated, odds ratio (OR) 3.96, (95% CI 1.63-9.66) and hyperplastic histology, OR 2.52 (95% CI 1.30-4.86)) in adjusted analyses. Conclusion: In this randomized trial, non-inferiority for cold snare polypectomy could not be demonstrated. Polyps with serrated histology are more prone to incomplete resection compared to adenomas. Cold snare polypectomy for small polyps can be used safely in routine colonoscopy practise.

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