OBJECTIVES: Adherence to colorectal cancer (CRC) screening strategies is imperfect and is ~40% for annual fecal immunochemical tests (FIT) and ~70% for triennial multi-target stool DNA (mt-sDNA) tests, based on cross-sectional data. Many microsimulation analyses have not considered differential adherence across screening modalities, which may lead to inaccurate conclusions regarding comparative effectiveness. We used the CRC-AIM microsimulation model to estimate the impact of varying adherence rates on the relative benefits of FIT and mt-sDNA screening.

METHODS: Sensitivity and specificity from DeeP-C trial data were used for screening inputs. Predicted outcomes of annual FIT and triennial mt-sDNA were simulated for individuals born in 1975 who were free of diagnosed CRC at age 40 and screened between ages 50-75. Adherence was set by assuming a fixed annual likelihood to comply ranging from 0-100%, in 10% increments. It was assumed that patients were offered a stool-based screening test yearly unless they were not due for screening. Predicted outcomes are per 1000 individuals versus no screening.

RESULTS: Each screening strategy yielded higher life-years gained (LYG) versus no screening. At perfect adherence, mt-sDNA resulted in 4.1% fewer LYG (LYG=302.2; colonoscopies=1856) versus FIT (LYG=315.2; colonoscopies =1915). At imperfect adherence rates of 70% for triennial mt-sDNA and 40% for annual FIT, mt-sDNA resulted in a 19.1% increase in LYG (288.9; colonoscopies=1724) versus FIT (242.5; colonoscopies=1218). LYG for FIT was more sensitive to per-unit change in adherence rates ([315.2−101.2]/[100%−10%]=2.4 LYG/unit change) than mt-sDNA (1.8 LYG/unit change). At equivalent adherence, mt-sDNA generally resulted in higher colonoscopies and lower stool testing vs FIT.

CONCLUSIONS: Stool-based CRC screening provides higher LYG vs no screening, regardless of adherence assumptions. The comparative effectiveness of FIT versus mt-sDNA screening changes dramatically when assuming adherence is <100%, with mt-sDNA outperforming FIT under adherence assumptions that are more consistent with available, although currently incomplete, real-world evidence.