Comparative effectiveness of screening strategies for Lynch syndrome

Journal of the National Cancer Institute
Afsaneh BarziNeal J Meropol

Abstract

Colorectal cancer is the second leading cause of cancer death in the United States. Approximately 3% of colorectal cancers are associated with Lynch Syndrome. Controversy exists regarding the optimal screening strategy for Lynch Syndrome. Using an individual level microsimulation of a population affected by Lynch syndrome over several years, effectiveness and cost-effectiveness of 21 screening strategies were compared. Modeling assumptions were based upon published literature, and sensitivity analyses were performed for key assumptions. In a two-step process, the number of Lynch syndrome diagnoses (Step 1) and life-years gained as a result of foreknowledge of Lynch syndrome in otherwise healthy carriers (Step 2) were measured. The optimal strategy was sequential screening for probands starting with a predictive model, then immunohistochemistry for mismatch repair protein expression (IHC), followed by germline mutation testing (incremental cost-effectiveness ratio [ICER] of $35 143 per life-year gained). The strategies of IHC + BRAF, germline testing and universal germline testing of colon cancer probands had ICERs of $144 117 and $996 878, respectively. This analysis suggests that the initial step in screening for Lynch Syndrom...Continue Reading

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