Evaluating key characteristics of ideal colorectal cancer screening modalities: the microsimulation approach.

Abstract Background and aims Screening for colorectal cancer (CRC) can effectively reduce CRC incidence and mortality. Besides colonoscopy, detection of biomarkers in stool, blood or serum, including fecal immunochemical test (FIT), ColoGuard, pro Epicolon and PolypDx have recently been advanced. We aimed to identify characteristics of theoretical, highly efficient screening tests and calculated effectiveness and cost-effectiveness of available screening tests. Methods Using the microsimulation-based colon modeling open-source tool (CMOST), we simulated 142,501 theoretical screening tests with variable assumptions for adenoma and carcinoma sensitivity, specificity, test frequency and adherence, and identified highly efficient tests outperforming colonoscopy. For available screening tests, we simulated 10 replicates of a virtual population of 2 million individuals, using epidemiological characteristics and costs assumptions of the United States. Results Highly efficient theoretical screening tests were characterized by high sensitivity for advanced adenoma and carcinoma and high patient adherence. All simulated available screening tests were effective at 100% adherence to screening and at expected real-world adherence rates. All tests were cost-effective below the threshold of 100,000 U.S. dollars per life year gained. With perfect adherence, FIT was the most effective and cost efficient intervention whereas Epi proColon was most effective at expected real-world adherence rates. In our sensitivity analysis, assumptions for patient adherence impacted strongest on effectiveness of screening. Conclusion Our microsimulation study identified characteristics of highly efficient theoretical screening tests and confirmed effectiveness and cost-effectiveness of colonoscopy and available urine-, blood- and stool-based tests. Better patient adherence results in superior effectiveness for CRC prevention in the whole population.