Longitudinal Data From a Large, Multitarget Stool DNA Colorectal Cancer Screening Program

Multitarget stool DNA (mt-sDNA) is an established stool-based colorectal cancer screening test, yet long-term performance is not well-described. We evaluated follow-up colonoscopy rates & quality, neoplasia yield, and repeat-testing adherence over 10 years with an integrated screening program.

We assembled a retrospective cohort of mt-sDNA tests (September 2014-July 2025) within a multisite health system. A validated large-language-model pipeline extracted colonoscopy, pathology, and quality end points from free-text reports. Detection outcomes (adenoma detection rate, advanced neoplasia, modified advanced adenoma [AA], sessile serrated lesion, and negative examinations) were calculated among high-quality examinations; adenocarcinoma, bowel preparation adequacy, and cecal intubation rate used all screening examinations. We assessed colonoscopy completion ≤1 year after positive mt-sDNA, follow-up colonoscopy findings, findings by time-to-colonoscopy, and adherence to repeat mt-sDNA after negative result.

Among 148,624 tests in 110,410 individuals, positivity was 13.6%. Of 19,506 positives, 65.1% completed colonoscopy within 12 months (median 82 days). Colonoscopy after a positive mt-sDNA had high yield: AA diagnosis was 30.7%; adenocarcinoma was 1.3%. Of patients who had colonoscopy within 3 years of a negative mt-sDNA test, 45.2% had adenoma/serrated lesion, 9.3% had AA and 0.5% had colon cancer. Adenoma detection rate after positive mt-sDNA (>50%) exceeded specialty society quality benchmarks and increased over time; Longer intervals (>6 months) to colonoscopy after a positive test were associated with higher AA (trend P = 0.001).After an initial negative mt-sDNA, only 35.3% were screened again by mt-sDNA testing within 3 years.

Over a decade, mt-sDNA screening achieved high colonoscopy quality but revealed critical gaps in the care cascade. One-third of positive tests lacked timely follow-up and nearly two-thirds of negative tests were not repeated on schedule, suggesting opportunities for system-level interventions.