Endoscopic surveillance for colorectal cancer and its precursor lesions in Lynch syndrome; time for some policy shifts?

Background: Numerous studies have demonstrated variations in colorectal cancer (CRC) incidence among Lynch Syndrome (LS)-associated mutation carriers, but limited data are available regarding tailoring surveillance- and treatment strategies. Main goal of this study was to estimate whether personalized care could be offered based on respectively germline pathogenic variants ( MLH1 , MSH2 , MSH6 or PMS2 ). Additionally the outcome from patient shared care for early CRC was investigated. Methods: Single center retrospective cohort analysis including patients with one of 4 groups of LS-associated pathogenic variants (PV) ( MLH1 , MSH2 , MSH6 or PMS2 ) who underwent surveillance colonoscopies between January 1978 and February 2024. Analyses were performed to identify differences in precursor lesion- or CRC incidence and treatment among the PVs. Results: From a cohort of 621 LS individuals 496 (133 MLH1 , 107 MSH2 , 180 MSH6 and 76 PMS2 ) could be included in this study. Analyses revealed that, despite adequate surveillance intervals and lower adenoma incidence, individuals with a gPV in MLH1 or MSH2 mutation carriers have higher CRC incidences compared to MSH6 or PMS2. Most detected CRC lesions were early stage T1 CRCs. Treatment for T1 CRC varied considerably, in 68% of the cases deviating from the current golden standard subtotal colectomy, with nearly equivalent recurrence rates. Discussion: Based on higher precursor lesion detection and lower CRC incidences in LS individuals with a gPV in MSH6 or PMS2 under biannual endoscopic surveillance, this study supports the potential for extended surveillance intervals in the latter group. As treatment for the detected T1 CRCs varied considerably with nearly equivalent recurrence rates, it emphases the feasibility of less invasive interventions for LS individuals.