Colonoscopic Surveillance in Lynch Syndrome Linked to Lower Mortality but Not Reduced Cancer Incidence

Background Lynch syndrome (LS) is a cancer susceptibility syndrome caused by germline pathogenic variants in DNA mismatch repair (MMR) genes. Due to increased risk of colorectal cancer (CRC), enhanced colonoscopic surveillance is recommended for heterozygote MMR-carriers. Objective Using a registry of English LS patients linked to digital National Health Service records, we aimed to assess adherence of MMR-carriers to national surveillance guidelines, and to determine the impact of surveillance on CRC incidence and mortality. Design We described the frequency of colonoscopies in 4,732 MMR-carriers and used logistic regression to determine predictors of surveillance adherence. For MMR-carriers with a record of surveillance and those without, we: estimated age-specific annual CRC incidence rates (AS-AIRs) and cumulative lifetime risks, assessed for stage-shift by comparing CRC stage distributions and stage-specific AS-AIRs, and estimated risks of death from CRC and any cause using Kaplan-Meier methods and Cox Proportional Hazards regression. Results Surveillance at a mean interval of [≤] 3 years (n=3028) was associated with a decrease in CRC-specific and all-cause mortality, without an associated change in total CRC incidence, even after multivariate adjustment. No strong evidence of stage-shift was observed. Colonoscopic surveillance at a mean interval of [≤] 2 years (n=1569) was associated with an increase in total CRC incidence. Incidence of early-stage cancers was also higher, with no corresponding decrease in late-stage cancers, which may reflect the short follow-up period or the impact of overdiagnosis. Conclusion The observed reduction in all-cause mortality amongst regularly-surveilled MMR-carriers may indicate an impact of surveillance on CRC-specific mortality, though in the context of a non-randomised study likely reflects the influence of selection bias.