Abstract

<div>Abstract<p>Few studies compare fecal immunochemical test (FIT) and multi-target stool DNA (mt-sDNA) outcomes in practice. We compared colonoscopy yield following FIT<sup>+</sup> or mt-sDNA<sup>+</sup> tests to colonoscopies without preceding stool tests in the comprehensive population-based New Hampshire Colonoscopy Registry (NHCR). Outcomes were any neoplasia and an ordered outcome: adenocarcinoma, advanced neoplasia (adenoma/serrated polyp ≥ 1 cm/villous/high-grade dysplasia), nonadvanced neoplasia, or normal. Our total sample included 306 mt-sDNA<sup>+</sup> (average age ± SD 67.0 ± 7.9), 276 FIT<sup>+</sup> (66.6 ± 8.7), and 50,990 colonoscopy-only patients (61.8 ± 8.1). Among average-risk patients (<i>N</i> = 240 mt-sDNA<sup>+</sup>, <i>N</i> = 194 FIT<sup>+</sup>, <i>N</i> = 26,221 colonoscopy only), mt-sDNA<sup>+</sup> patients had a higher risk for any neoplasia (67.1%) compared with FIT<sup>+</sup> (54.6%, <i>P</i> = 0.00098) or colonoscopy (40.8%, <i>P</i> < 0.0001). Severity of findings and histology subtypes differed across the three groups (<i>P</i> < 0.0001 for both), with a higher yield of advanced findings in mt-sDNA<sup>+</sup> patients. In particular, clinically relevant serrated polyps (hyperplastic polyps ≥10 mm/traditional serrated adenomas/sessile serrated polyps) were detected at a higher frequency in mt-sDNA<sup>+</sup> patients as compared with FIT<sup>+</sup> or colonoscopy-only patients. Even after adjustment, patients with positive mt-sDNA [OR = 2.82; 95% confidence interval (CI), 2.00–4.02] or FIT<sup>+</sup> tests (OR = 1.67; 95% CI, 1.19–2.36) were more likely to have histologically more advanced findings than colonoscopy alone. At follow-up colonoscopy, mt-sDNA<sup>+</sup> tests were more likely to predict neoplasia than FIT<sup>+</sup>, largely due to increased detection of serrated polyps.</p><p><b>Prevention Relevance:</b> Colorectal cancer screening options include colonoscopy and stool-based tests, including the fecal immunochemical test (FIT) and the multi-target stool DNA (mt-sDNA) test which, if positive, must be followed by a colonoscopy. Assessing “real-world” outcomes of colonoscopies following positive stool tests can inform their clinical use.</p><p><i><a href="https://aacrjournals.org/cancerpreventionresearch/article/doi/10.1158/1940-6207.CAPR-22-0213" target="_blank">See related Spotlight, p. 417</a></i></p></div>

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