Model-based evaluation of colorectal cancer screening effectiveness: three rounds of multitarget stool DNA testing...

Several colorectal cancer (CRC) screening modalities are guideline-recommended in the United States but differ in screening interval and real-world adherence. Accordingly, single-round test performance may not reflect cumulative effectiveness over time. This study compared the 10-year longitudinal outcomes of two CRC screening strategies-triennial next-generation multitarget stool DNA testing (ng mt-sDNA) and decennial screening colonoscopy.

The validated, microsimulation-based Colorectal Cancer and Adenoma Incidence and Mortality (CRC-AIM) model was used to estimate 10-year cumulative outcomes for two guideline-recommended screening strategies: triennial ng mt-sDNA and decennial colonoscopy. Model inputs included test performance and real-world adherence. Outcomes included CRC and precancerous lesions detected, CRC mortality reductions, and life-years gained (LYG). Sensitivity analyses examined the effects of varying screening adherence and follow-up colonoscopy adherence.

Over 10 years per 1,000 individuals offered screening, ng mt-sDNA detected 13% more precancerous lesions and 11% more CRC cases than colonoscopy, with a greater proportion of CRCs identified through screening rather than symptomatic detection. ng mt-sDNA achieved greater CRC mortality reduction (33% vs 20%) and 62% more life-years gained, with consistent findings across sensitivity analyses.

With real-world adherence, screening with triennial ng mt-sDNA demonstrates superior cumulative effectiveness compared with decennial colonoscopy, driven by higher adherence and favorable longitudinal performance. These findings support expanded use of noninvasive stool-based screening to reduce CRC mortality and alleviate colonoscopy capacity constraints. Broader adoption of ng mt-sDNA may enhance population-level CRC prevention by increasing participation and improving early detection.