The predicted effect and cost-effectiveness of tailoring colonoscopic surveillance according to mismatch repair gene in patients with Lynch syndrome.

Lynch syndrome-related colorectal cancer (CRC) risk substantially varies by mismatch repair (MMR) gene. We evaluated the health impact and cost-effectiveness of MMR gene-tailored colonoscopic surveillance. We first estimated sex- and MMR gene-specific cumulative lifetime risk of first CRC without colonoscopic surveillance using an optimization algorithm. Next, we harnessed these risk estimates in a microsimulation model, "Policy1-Lynch," and compared 126 colonoscopic surveillance strategies against no surveillance. The most cost-effective strategy was 3-yearly surveillance from age 25 to 70 years (pathogenic variants [path_] in MLH1 [path_MLH1], path_MSH2) with delayed surveillance for path_MSH6 (age 30-70 years) and path_PMS2 (age 35-70 years) heterozygotes (incremental cost-effectiveness ratio = Australian dollars (A) $8,833/life-year saved). This strategy averted 60 CRC deaths (153 colonoscopies per death averted) over the lifetime of 1000 confirmed patients with Lynch syndrome (vs no surveillance). This also reduced colonoscopies by 5% without substantial change in health outcomes (vs nontailored 3-yearly surveillance from 25-70 years). Generally, starting surveillance at age 25 (vs 20) years was more cost-effective with minimal effect on life-years saved and starting 5 to 10 years later for path_MSH6 and path_PMS2 heterozygotes (vs path_MLH1 and path_MSH2) further improved cost-effectiveness. Surveillance end age (70/75/80 years) had a minor effect. Three-yearly surveillance strategies were more cost-effective (vs 1 or 2-yearly) but prevented 3 fewer CRC deaths. MMR gene-specific colonoscopic surveillance would be effective and cost-effective.

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Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of Interest K.C. is co–principle investigator of an investigator-initiated trial of cervical screening, “Compass”, run by The Australian Centre for the Prevention of Cervical Cancer (ACPCC), which is a government-funded not-for-profit charity; “Compass” receives infrastructure support from the Australian government and the ACPCC has received equipment and a funding contribution from Roche Molecular Diagnostics, USA. She is also co–principle investigator on a major implementation program Elimination of Cervical Cancer in the Western Pacific which has received support from the Minderoo Foundation and the Frazer Family Foundation, and equipment donations from Cepheid Inc. She also receives support for a range of other Australian and international government projects including support from philanthropic organizations, WHO, and government agencies related to cervical cancer control. K.C. is a Chair or member of a number of government or meetings convened by the World Health Organization (WHO), or philanthropic organizations such as Bill and Melinda Gates Foundation (BMGF). N.T. is a recipient of a Cancer Institute NSW Career Development Fellowship and a Cancer Australia Priority-driven Collaborative Cancer Research Scheme project grant. All other authors declare no conflicts of interest.