Detection of High-Risk Sessile Serrated Lesions: Multitarget Stool DNA Versus CT Colonography.

Abstract

<b>BACKGROUND.</b> The serrated pathway for colorectal cancer (CRC) development is increasingly recognized. Sessile serrated lesions (SSLs) that are large (≥ 10 mm) and/or have dysplasia (i.e., high-risk SSLs) are at higher risk of progression to CRC. Detection of SSLs is challenging given their predominantly flat and right-sided location. The yield of noninvasive screening tests for detection of high-risk SSLs is unclear. <b>OBJECTIVE.</b> The aim of this study was to compare noninvasive screening detection of high-risk SSLs between the multitarget stool DNA (mt-sDNA) test and CT colonography (CTC). <b>METHODS.</b> This retrospective study included 7974 asymptomatic adults (4705 women, 3269 men; mean age, 60.0 years) who underwent CRC screening at a single center by mt-sDNA from 2014 to 2019 (<i>n</i> = 3987) or by CTC from 2009 to 2019 (<i>n</i> = 3987). Clinical interpretations of CTC examinations were recorded. Subsequent colonoscopy findings and histology of resected polyps were also recorded. Chi-square or two-sample <i>t</i> tests were used to compare results between mt-sDNA and CTC using 6-mm and 10-mm thresholds for test positivity. <b>RESULTS.</b> The overall colonoscopy referral rate for a positive screening test was 13.1% (522/3987) for mt-sDNA versus 12.2% (487/3987; <i>p</i> = .23) and 6.5% (260/3987; <i>p</i> < .001) for CTC at 6-mm and 10-mm thresholds, respectively. The PPV for high-risk SSLs was 5.5% (26/476) for mt-sDNA versus 14.4% (66/457; <i>p</i> < .001) and 25.9% (63/243; <i>p</i> < .001) for CTC at the 6-mm and 10-mm thresholds, respectively. The overall screening yield of high-risk SSLs was 0.7% (26/3987) for mt-sDNA versus 1.7% (66/3987; <i>p</i> < .001) and 1.6% (63/3987; <i>p</i> < .001) for CTC at 6-mm and 10-mm thresholds, respectively. <b>CONCLUSION.</b> CTC at 6-mm and 10-mm thresholds had significantly higher yield and PPV for high-risk SSLs compared with mt-sDNA. <b>CLINICAL IMPACT.</b> The significantly higher detection of high-risk SSLs by CTC than by mt-sDNA should be included in discussions with patients who decline colonoscopy and opt for noninvasive screening.