Colorectal cancer-screening models commonly assume 100% adherence, which is inconsistent with real-world experience. The influence of adherence to initial stoolbased screening [fecal immunochemical test (FIT), multitarget stool DNA (mt-sDNA)] and follow-up colonoscopy (after a positive stool test) on colorectal cancer outcomes was modeled using the Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model. Average-risk individuals without diagnosed colorectal cancer at age 40 undergoing annual FIT or triennial mt-sDNA screening from ages 50 to 75 were simulated. Primary analyses incorporated published mt-sDNA (71%) or FIT (43%) screening adherence, with follow-up colonoscopy adherence ranging from 40% to 100%. Secondary analyses simulated 100% adherence for stool-based screening and colonoscopy follow- up (S1), published adherence for stool-based screening with 100% adherence to colonoscopy follow-up (S2), and published adherence for both stool-based screening and colonoscopy follow-up after positive mt-sDNA (73%) or FIT (47%; S3). Outcomes were life-years gained (LYG) and colorectal cancer incidence and mortality reductions (per 1,000 individuals) versus no screening. Adherence to colonoscopy follow-up after FIT had to be 4%-13% higher than mt-sDNA to reach equivalent LYG. The theoretical S1 favored FIT versus mt-sDNA (LYG 316 vs. 297; colorectal cancer incidence reduction 68% vs. 64%; colorectal cancer mortality reduction 76% vs. 72%). The more realistic S2 and S3 favored mt-sDNA versus FIT (S2: LYG 284 vs. 245, colorectal cancer incidence reduction 61% vs. 50%, colorectal cancer mortality reduction 69% vs. 59%; S3: LYG 203 vs. 113, colorectal cancer incidence reduction 43% vs. 23%, colorectal cancer mortality reduction 49% vs. 27%, respectively). Incorporating realistic adherence rates for colorectal cancer screening influences modeled outcomes and should be considered when assessing comparative effectiveness.
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