• Afsaneh Barzi, Sarmad Sadeghi, Michael W Kattan, and Neal J Meropol.
• Department of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (AB, SS); Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH (MWK); Cleveland Clinic Lerner College of Medicine, Cleveland, OH (MWK); Department of Epidemiology and Biostatistics (MWK) and Department of Medicine (NJM), School of Medicine, and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH; Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH (NJM).
• J. Natl. Cancer Inst. 2015 Apr 1; 107 (4).

BackgroundColorectal 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.MethodsUsing 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.ResultsThe 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.ConclusionsThis analysis suggests that the initial step in screening for Lynch Syndrome should be the use of predictive models in probands. Universal tumor testing and general population screening strategies are not cost-effective. When family history is unavailable, alternate strategies are appropriate. Documentation of family history and screening for Lynch Syndrome using a predictive model may be considered a quality-of-care measure for patients with colorectal cancer.© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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