Table 8. Clinical Practice Guidelines for Diagnosis and Colon Surveillance of Familial Adenomatous Polyposis (FAP) continued...
The EGAPP analysis made several assumptions, including (1) IHC and MSI will not detect all LS patients and (2) not all patients with CRC will opt for testing.
Results are available from a Markov model that incorporated the risks of colorectal, endometrial, and ovarian cancers to estimate the effectiveness and cost-effectiveness of strategies to identify LS among persons with newly diagnosed CRC. The strategies incorporated in the model were based on clinical criteria, prediction algorithms, and tumor testing or up-front germline mutation testing followed by directed screening and risk-reducing surgery. Similar to the EGAPP working group, IHC followed by BRAF mutation testing was the preferred strategy in this study. An incremental cost-effectiveness ratio of $36,200 per life year gained resulted from this strategy. In this model, the number of relatives tested (3 to 4) per proband was a critical determinant of both effectiveness and cost-effectiveness.
A different approach based on risk assessments of 100,000 simulated individuals representative of the U.S. population who were tracked from age 20 and exposed to 20 different screening strategies has been reported. In this study, the strategies involved risk assessment at different ages utilizing the PREMM126 model followed by mutation analysis for MLH1, MSH2, MSH6, and PMS2 in individuals whose mutation risk threshold exceeded 0%, 2.5%, 5%, or 10%. In individuals whose risk assessment (starting at age 25, 30, or 35 years) for carrying a mutation exceeded 5%, colorectal and endometrial cancers in mutation carriers were reduced by 12.4% and 8.8%, respectively. In the whole population, this strategy increased the quality adjusted life-years by 135 years per 100,000 individuals with an average cost-effectiveness ratio of $26,000. The authors suggested that the outlined strategy was more cost effective than current practice and could improve health care outcomes.
Diagnostic strategies for all individuals diagnosed with endometrial cancer
Based on a Markov mathematical model, a strategy of performing IHC for MMR protein expression in all patients with endometrial cancer, irrespective of the age at diagnosis, who have a first-degree relative with endometrial cancer, was reported to be cost-effective in the detection of LS in patients with LS-related cancer. (Refer to the Genetic testing section of this summary for more information about performing IHC for MMR protein expression.) In this study, incremental cost-effectiveness ratio was defined as the additional cost of a specific strategy divided by its health benefit compared with an alternative strategy. In this model, the strategy of performing IHC on the tumor from all patients diagnosed with LS-related cancer who have a first-degree relative with endometrial cancer had an incremental cost ratio of $9,126 per year of life gained relative to the least-costly strategy, which was genetic testing on all women diagnosed with endometrial cancer younger than 50 years with at least one first-degree relative with LS-related cancer.