Evaluating colonoscopy screening intervals in patients with Lynch syndrome from a large Canadian registry

Abstract

Background: Lynch syndrome (LS) screening guidelines originally recommended colonoscopy every 1 to 2 years, beginning between the ages of 20 and 25 years. Recent studies have questioned the benefits of these short screening intervals in preventing colorectal cancer (CRC). Our goal is to determine how colonoscopy screening intervals impact CRC in patients with LS.

Methods: We analyzed the demographics, screening practices, and outcomes of patients with LS identified through the clinic based Familial Gastrointestinal Cancer Registry at the Zane Cohen Centre, Sinai Health System, Toronto, Canada.

Results: A total of 429 patients with LS were identified with median follow-up of 9.2 years; 44 developed CRC. We found a positive trend between shorter screening intervals and the number of adenomas detected during colonoscopy. Any new adenoma detected at screening decreased 10-year CRC incidence by 11.3%. For MLH1 carriers, a screening interval of 1-2 years vs 2-3 years led to a 20-year cumulative CRC risk reduction of 28% and 14% in females and males, respectively. For MSH2 carriers, this risk reduction was 29% and 17%, respectively, and for male MSH6 carriers 18%. Individuals without any adenomas detected (53.4% of LS carriers) had an increased 20-year CRC risk of 25.7% and 57.2% for women and men, respectively, compared with those diagnosed with adenomas at screening.

Conclusions: The recommended colonoscopy screening interval of 1-2 years is efficient at detecting adenomas and reducing CRC risk. The observation that 53.4% of LS patients never had an adenoma warrants further investigation about a possible adenoma-free pathway.

Figure 1.

Number of adenomas detected during follow-up with respect to colonoscopy screening intervals in male and female patients with LS. Each solid line represents the predicted number of adenomas obtained from step 1 of the analysis for a fictive patient with LS, with an average age at first colonoscopy of 41.3 years, no adenoma detected at the first colonoscopy, and with a fixed screening interval of 1, 2, 3, or 4 years, which remains the same over the study period. Each curve starts at the time of the second colonoscopy (ie, 1, 2, 3, and 4 years for the screening intervals of ≤1, 1-2, 2-3, and >3 years, respectively). Dotted lines represent the 95% confidence intervals. LS = Lynch syndrome.

Figure 2.

Cumulative incidence of CRC in male and female patients with LS from the first colonoscopy visit to 20 years of follow-up: A) by screening interval and history of adenoma; B) by gene-specific pathogenic variant status and colonoscopy screening intervals. Each solid curve represents CRC risk for a fictive patient with LS, with an average age at first colonoscopy of 41.3 years, no adenoma detected at the first colonoscopy, and with a fixed screening interval of 1, 2, 3, or 4 years, which remains the same over the study period. Dotted lines represent the 95% confidence intervals. CI = confidence interval; CRC = colorectal cancer; LS = Lynch syndrome.