The predicted effect and cost-effectiveness of tailoring colonoscopic surveillance according to mismatch repair gene in patients with Lynch syndrome
- Author(s)
- Kang, YJ; Caruana, M; McLoughlin, K; Killen, J; Simms, K; Taylor, N; Frayling, IM; Coupe, VMH; Boussioutas, A; Trainer, AH; Ward, RL; Macrae, F; Canfell, K;
- Details
- Publication Year 2022-09,Volume 24,Issue #9,Page 1831-1846
- Journal Title
- Genetics in Medicine
- Publication Type
- Research article
- Abstract
- PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: MMR gene-specific colonoscopic surveillance would be effective and cost-effective.
- Keywords
- Adult; Aged; Australia; Colonoscopy; *Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis/epidemiology/genetics; Cost-Benefit Analysis; DNA Mismatch Repair/genetics; Humans; Middle Aged; Mismatch Repair Endonuclease PMS2/genetics; MutL Protein Homolog 1/genetics; MutS Homolog 2 Protein/genetics; Clinical practice guidelines; Colorectal cancer; Cost-effectiveness; Lynch syndrome
- Department(s)
- Surgical Oncology; Familial Cancer Centre
- PubMed ID
- 35809086
- Publisher's Version
- https://doi.org/10.1016/j.gim.2022.05.016
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-12-19 03:18:25
Last Modified: 2024-12-19 03:23:08