Impact of surveillance colonoscopy on colorectal cancer incidence and mortality in Lynch syndrome: a national observational cohort study of patients in the English NHS 2010–2022
Catherine Huntley, Lucy Loong, Corinne Mallinson, Tameera Rahman, Beth Torr, Sophie Allen, Isaac Allen, Hend Hassan, Yvonne Walburga Joko Fru, Daniela Tataru, Lizz Paley, Sally Vernon, Richard S Houlston, David Muller, Fiona Lalloo, Adam C Shaw, John Burn, Eva J A Morris, Marc Tischkowitz, Antonis C Antoniou, Paul D P Pharoah, Kevin Monahan, Steven Hardy, Clare TurnbullBackground
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 patients with LS 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 4732 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, spectrum bias, or the impact of overdiagnosis.
Conclusion
The observed reduction in all-cause mortality among regularly surveilled MMR carriers may indicate an impact of surveillance on CRC-specific mortality, though in the context of a non-randomised study could also reflect the influence of selection bias.