Which Lynch syndrome screening program can be implemented? Systematic review of economic evaluations

Background Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC). CDC’s Office of Public Health Genomics recognizes that widespread implementation of LS genetic screening can significantly reduce cancer morbidity and mortality in mutation carriers. The purpose of this systematic review is to identify clinically and economically feasible LS screening programs which may be implemented in real-world. Methods Full economic evaluations of programs containing genetic testing strategies aimed at identifying and managing LS in different target populations were included; health outcomes should be estimated in terms of life-years gained (LYG) or quality-adjusted life-years (QALY). Relevant studies (from inception to January 2017) were identified using the most important scientific and economic databases. Results 20 of 378 studies initially retrieved were included in the systematic review. According to the screening target population, 6 LS screening program categories were identified: CRC-based, endometrial cancer-based, general population-based, LS families’ registry-based, cascade testing-based, and genetics clinic-based LS screening program. Regarding CRC-based LS program, 3 additional subcategories were identified: universal, age-targeted and selective. In 5 studies universal programs based on immunohistochemistry, alone or in combination with the BRAF test, were cost-effective in comparison with no screening (<$50,000/LYG or QALY), whilst in 2 studies they showed incremental costeffectiveness ratios exceeding willingness to pay thresholds when compared to selective programs. In 2 studies age-targeted programs with cut-off of 70 years old were cost-effective when compared to age-targeted programs with lower age thresholds. Conclusions Universal or< 70 years old age-targeted CRC-based LS screening programs should be implemented in real-world to assess their actual impact in terms of both costs and effectiveness.