Traditional serrated adenomas associated with risk of subsequent high-risk polyps and colorectal cancer

Introduction: Traditional serrated adenoma (TSA) is a rare yet established precursor to colorectal cancer (CRC). The risk of colorectal neoplasia after TSA removal remains unclear. Methods: We identified participants without polyps or with TSAs during index colonoscopy from the Mass General Brigham Colonoscopy Cohort (2007-2023). Participants were prospectively followed for recurrence of high-risk polyps and incidence of CRC. We used time-varying multivariable-adjusted Cox proportional hazards model to estimate the risk of CRC and high-risk polyps associated with baseline diagnosis of TSAs. Results: We identified 109,218 participants without polyps and 252 with TSAs, of whom 35,124 (32%) and 139 (55%) had undergone a follow-up colonoscopy, respectively. TSAs were predominantly located in the distal colon (35%) and rectum (38%), with approximately half sized <10mm. TSAs tended to demonstrate as a single lesion (84%) but coexist with other types of polyps (70%). Compared to participants without polyps, those with TSAs had higher risk of developing high-risk polyps, high-risk adenomas, high-risk serrated polyps, and CRC, with the hazard ratio (HR) and 95% confidence interval (CI) of 3.31 (2.35-4.66), 3.07 (2.12-4.44), 6.66 (3.79-11.71), and 7.23 (2.23-23.44), respectively. The risk elevation of high-risk polyps peaked at three years post-TSA removal (HR=10.85, 95% CI, 6.36-18.52). Among recurrent polyps following TSA removal, 54% (52/96) occurred in the proximal colon and 69% (66/96) were serrated polyps. Discussion: Patients with TSA removal had an elevated risk of colorectal neoplasia, particularly within three years following TSA removal, supporting the current U.S. recommendations for a surveillance colonoscopy at three years.