Gut · 2026
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.
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Huntley Catherine, Loong Lucy, Mallinson Corinne, Rahman Tameera, Torr Beth, Allen Sophie, Allen Isaac, Hassan Hend, Fru Yvonne Walburga Joko, Tataru Daniela, Paley Lizz, Vernon Sally, Houlston Richard S, Muller David, Lalloo Fiona, Shaw Adam C, Burn John, Morris Eva J A, Tischkowitz Marc, Antoniou Antonis C, Pharoah Paul D P, Monahan Kevin, Hardy Steven, Turnbull Clare
Аннотация
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 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.
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.