COST EFFECTIVENESS OF GENETIC TESTING FOR LYNCH SYNDROME AMONG NEWLY DIAGNOSED COLORECTAL CANCER PATIENTS AND THEIR FIRST-DEGREE RELATIVES

Purpose: Lynch syndrome (LS) is an autosomal dominant disorder that carries a 30-40% probability of developing colorectal cancer (CRC) by age 70. Our objective was to estimate the cost effectiveness of genetic testing for LS among newly diagnosed CRC patients and mutation testing among their first-degree relatives, who have a 50% probability of also having LS. 

 Methods: We developed a cost effectiveness model from the health care system perspective of four screening strategies applied to all newly diagnosed cases of CRC: (1) diagnostic testing (sequencing and deletion analysis) for all, (2) microsatellite instability (MSI) testing then diagnostic testing among those with MSI-high results, (3) immunohistochemistry (IHC) testing then diagnostic testing among those with absent protein stains, and (4) IHC then BRAF mutation testing among a subset and then diagnostic testing. We assumed that first-degree relatives (siblings and children) aged ≥ 20 years would be offered targeted testing for the family mutation (~4 relatives per patient). The model includes the costs of genetic counseling and testing and the lifetime costs for colonoscopies and CRC treatment. Future costs and outcomes were discounted at 3%. Data sources included published literature, SEER data, and an Evaluation of Genomic Applications in Practice and Prevention (EGAPP) supplemental evidence review.

Results: The most cost effective strategy was strategy 4, with an incremental cost effectiveness ratio (ICER) of $4,557 per life-year saved. Strategy 3 was subject to extended dominance. The most effective but costly screening strategy was strategy 1, with an ICER of $191,129 per life-year saved. Strategy 2 had an ICER of $183,685 per life-year saved. One-way sensitivity analysis of the results of the four strategies showed that the choice of the cost effective strategy did not change as parameters were varied. For the most cost effective strategy, as the number of relatives located ranged from 2 to 8, the ICER ranged from $11,465 to $1,102 per life-year saved, respectively, and as the uptake of colonoscopy ranged from 20% to 90% the ICER ranged from $20,528 to $3,895 per life-year saved.

Conclusion: Genetic testing of newly diagnosed CRC patients and the relatives of patients with LS is likely to be cost effective from a health care system perspective, depending on the testing strategy adopted.