Raising the Age for Starting Colonoscopy to 35 Years for Individuals With path_MSH6 Carriers May Lead to Missed Opportunities for Detecting Advanced Neoplasia in a Notable Percentage of Carriers.

Background: Recent guidelines for Lynch syndrome recommend starting a colonoscopy at 30-35 years for path_MSH6 carriers. This study aimed to measure the rate of advanced neoplasia (AN) in these carriers up to age 35.

Methods: A multicenter retrospective analysis of endoscopic and pathological data was performed for path_MSH6 carriers who underwent endoscopic surveillance at specialized high-risk clinics. Advanced colorectal neoplasia was defined as colorectal cancer (CRC) or advanced polyp (AP).

Results: The study included 197 participants from 141 unrelated families, 60.9% of whom were women, and 90.9% completed follow-up by the age of 35 years or reached the outcome. Eleven individuals (5.58%; 1/18) were diagnosed with AN at 35, with a median age of 29 (interquartile range: 26-31). Among these cases, 6 (3.05%) had AP and 5 (2.54%) were diagnosed with CRC. Among the CRC cases, 1 was classified as American Joint Committee on Cancer stage I, 3 as stage IIA, and 1 as stage IV. Four of the 11 AN cases were detected through screening, accounting for 36.3% of AN cases and 2.03% of the total cohort (1 of 50). This included 1 case of American Joint Committee on Cancer stage I and 3 cases of AP.

Conclusions: Our findings suggest that the recommendation to raise the age for initiating colonoscopy to 35 years for path_MSH6 carriers merits careful consideration because there is a possibility that AN may not be detected. Given the limited size of our study and the potential for ascertainment bias, we encourage further research to explore and validate our findings.