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

Abstract

Background/Aims: Programmatic screeningfor 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, includingthe 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.