Stool DNA-based SDC2 Methylation Test for the Screening of Colorectal Neoplasia in an Asymptomatic, Average-Risk Population

Background/Aims: Programmatic screening for colorectal cancer (CRC) could maximize the impact of screening in the average-risk population, but the diagnostic performance of a stool DNA-based Syndecan-2 methylation (meSDC2) test has only been reported in case-control studies or high-risk populations. This study examined the performance of a stool DNA-based meSDC2 test for CRC in an average-risk population from a real-world setting. Methods: This retrospective, multicenter study included consecutive asymptomatic, average-risk individuals for CRC who completed a meSDC2 stool test at 18 hospitals. The clinical performance of the meSDC2 stool test, including the positive rate, adherence to con­firmatory colonoscopy, and the positive predictive value (PPV) for colorectal neoplasia (CRN), was assessed. Results: Over 54 months, 4,910 individuals completed the meSDC2 stool test, with 249 (5.1%) testing positive. The colonoscopy com­pliance rate after a positive test was 61.0% (n=152). Among 121 individuals with available colonoscopy data, the PPV for any CRN, advanced neoplasia, and CRC were 39.7%, 12.4%, and 2.5%, respectively. Colonoscopy after a positive meSDC2 test ensured a high-quality examination, as reflected by the 100% cecal intubation rate, 97.5% adequate preparation quality, and an average with­drawal time of 11.2 min. Among those with a positive meSDC2 test, a family history of CRC was a significant predictor of any CRN (p=0.029) and advanced neoplasia (p=0.003). Conclusions: A stool DNA-based meSDC2 test in average-risk individuals for CRC revealed a high PPV for any CRN in a real-world set­ting, highlighting its potential as a screening modality in programmatic CRC screening.