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Background and aims: Patients who previously had a normal colonoscopy may subsequently undergo colorectal cancer (CRC) screening with multitarget stool DNA (mt-sDNA) testing. The yield of advanced neoplasia following a positive mt-sDNA test in this subgroup is not well defined. We compared colonoscopy outcomes after positive mt-sDNA tests in patients with and without a prior normal colonoscopy. Methods: We conducted a registry-based analysis using data from the population-based New Hampshire Colonoscopy Registry (NHCR). The primary outcome was an ordered four-level categorical variable reflecting colonoscopy findings: CRC, advanced colorectal neoplasia, non-advanced colorectal neoplasia, and no neoplasia. Ordinal logistic regression models were used to evaluate the association between prior normal colonoscopy and severity of findings. Results: Patients with a prior normal colonoscopy (n=739) were approximately half as likely to have more advanced findings compared with patients without a prior colonoscopy (n=994); prior normal colonoscopy was associated with lower odds of more advanced versus less advanced outcomes (OR 0.51; 95% CI 0.41–0.62; P < 0.001). However, the absolute prevalence of advanced colorectal neoplasia among patients with a previous colonoscopy remained substantial (19.1%; 95% CI 16.3–22.1%). Conclusions: Although prior normal colonoscopy is associated with lower odds of advanced findings after a positive mt-sDNA test, the residual prevalence of advanced neoplasia remains clinically meaningful. Regardless of prior screening history, there is a high yield of neoplasia, which could be attributed in part due to missed lesions on the prior colonoscopy. Our data provide potential benchmarks for expected lesion yield in this population.
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Anderson et al. (2026) studied this question.
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