Cost-Effectiveness of Lynch Syndrome Identification Strategies in Individuals With Colorectal Cancer and the Impact on At-Risk Relatives

Abstract

Background & aims: Universal screening for Lynch syndrome (LS) is recommended for all patients diagnosed with colorectal cancer (CRC). A benefit of LS screening in CRC is cascade testing (CT), whereby at-risk relatives are tested for the familial pathogenic LS variant and undergo intensive surveillance for CRC prevention/early detection if identified with LS. There is not yet universal uptake of CT; we quantify the impact on CRC-related outcomes in first-degree relatives (FDRs).

Methods: We developed a microsimulation model to quantify the impact of CT on CRC incidence and mortality in FDRs (parents, siblings, children) of individuals with CRC screened for LS. For FDRs, the primary outcome was the number of CRC cases and CRC-related deaths, by age of relative; secondary outcomes included life-years gained, quality-adjusted life-years, number of colonoscopies, and costs associated with CT, surveillance, and cancer care.

Results: With CT for all eligible FDRs, we estimate 61.0% decrease in CRC cases and 78.5% decrease in CRC mortality. Although CT led to an average 11 more lifetime colonoscopies, there was modest increase in life-years gained and quality-adjusted life-years and decreased costs because of savings from cancer treatment.

Conclusions: This model quantifies the benefits of CT for at-risk FDRs of newly identified individuals with CRC and LS. The decrease in CRC incidence across generations can be used to facilitate discussions with relatives to improve uptake of CT. Further studies to optimize the uptake of CT are paramount to decrease risk of CRC in LS.

Keywords: Cascade Testing; Colorectal Cancer; Genetics; Lynch Syndrome.