Return of Mailed Multitarget Stool DNA Test Kits and Subsequent Colorectal Cancer Incidence in the United States: A Retrospective Cohort Study

INTRODUCTION: Completion of colorectal cancer (CRC) screening is essential to realizing the benefits of early detection and prevention; however, many individuals do not complete screening after a test is provided. The association between screening completion and subsequent CRC incidence remains poorly understood. We evaluated the association between multitarget stool DNA (mt-sDNA) test kit return and CRC incidence among average-risk adults. METHODS: This retrospective cohort study, linking claims data from Komodo Health with Abbott laboratory data, included adults aged 45-85 years who received an mt-sDNA kit between January 1, 2017, and December 31, 2019 (based on linked laboratory and claims data). The primary outcome was incident CRC identified using claims-based diagnosis codes. Propensity score-matched (PSM) and inverse probability treatment-weighted (IPTW) analyses assessed robustness to confounding. Adjusted incidence rate ratios (IRRs) were estimated using Poisson regression and hazard ratios (HRs) using Cox proportional hazards models. RESULTS: The cohort included 2,574,759 adults (60.5% female, 38.5% male; 68.2% White, 8.2% Black/African American, 6.5% Hispanic, 2.6% Asian/Pacific Islander, 14.4% other/unknown race), who contributed over 14 million person-years of follow-up. CRC incidence was lower among kit returners than non-returners (248.95 vs 301.89 per 100,000 person-years). In adjusted analyses, mt-sDNA kit return was associated with 55% lower CRC incidence versus non-return [IRR 0.45; 95% confidence interval (CI) 0.45-0.46; p < 0.0001], with similar findings in PSM (IRR 0.58; 95% CI 0.57-0.59) and IPTW analyses (IRR 0.28; 95% CI 0.28-0.28). Supportive time-to-event analyses demonstrated directionally consistent associations, with mt-sDNA kit return associated with improved CRC-free survival (HR 0.76; 95% CI 0.74-0.78; p < 0.0001). CONCLUSIONS: In this large retrospective cohort study, mt-sDNA screening completion was consistently associated with lower CRC incidence across unmatched, PSM, and IPTW analyses. These findings support strategies to improve stool-based CRC screening completion to maximize the population-level benefits of CRC screening programs.