Cost-effectiveness of immunohistochemistry for mismatch repair testing on endometrial intraepithelial neoplasia for early diagnosis of Lynch syndrome.

e17629 Background: Lynch Syndrome (LS) is an autosomal dominant hereditary cancer syndrome characterized by mismatch repair protein (MMR) deficiency that increases the lifetime risk of cancers, including colorectal, endometrial, and ovarian cancers. Endometrial intraepithelial neoplasia (EIN) is a well-established precursor lesion to endometrial cancer (EC). There is evidence that EIN is a precursor to LS-associated EC, however there is currently no recommendation for immunohistochemistry (IHC) testing of EIN for loss of MMR protein expression to facilitate early diagnosis of and screening for additional LS-associated cancers. Methods: A decision analysis with Markov model was created with the initial decision point of IHC testing for MMR deficiency at time of EIN diagnosis or standard care with no IHC. Probabilities, costs, and utilities in the model were drawn from the published literature. Patients in the pre-operative IHC testing arm could either have a positive result, undergo genetic counseling and germline genetic testing, or a negative result and receive standard of care for EIN with total laparoscopic hysterectomy and bilateral salpingectomy (TLH-BS). Patients with a pre-operative diagnosis of germline LS underwent laparoscopic total hysterectomy and bilateral salpingo-oophorectomy (TLH-BSO) as additional risk reduction for ovarian cancer. Patients with a negative or unknown pre-operative diagnosis of LS underwent TLH-BS. Patients that did not have pre-operative IHC but were simulated to have a post-operative diagnosis of EC on final surgical specimen, which occurs in 30-40% of hysterectomies for EIN, underwent post-operative IHC testing and followed the same pathway of genetic counseling and germline testing based on IHC result. All patients diagnosed with LS were simulated to undergo enhanced colorectal cancer screening. A starting age of 45, cycle length of 1 year, and a time horizon of 50 years was used. Results: In our model pre-operative IHC testing was associated with an incremental cost effectiveness ratio of $20,671 per quality adjusted life year (QALY). In a one-way sensitivity analysis we varied the percentage of MMR loss on IHC for EIN from 3% to 22% based on reported rates in the literature. We found that performing pre-operative IHC on EIN remained cost-effective, though the overall cost of pre-operative testing increased with increasing prevalence of MMR loss on IHC for EIN. Conclusions: Pre-operative IHC for MMR loss on EIN appears to be a cost-effective strategy for identifying additional cases of LS. The additional QALYs accrued from this testing strategy are from improved operative planning and preventative screening for additional LS-associated cancers. Future work could additionally examine the costs and benefits from cascade testing of first-degree relatives and associated cancer prevention.