Abstract Introduction Stool DNA testing based on methylated syndecan-2 (mSDC2) is a potential novel non-invasive screening test for colorectal cancer (CRC). This study aimed to assess its positive predictive value (PPV) in real-world practice. Methods This study retrospectively recruited consecutive patients with positive stool DNA-based SDC2 methylation tests from 18 hospitals between November 2016 and July 2021. Included patients were classified into the average-risk equivalent or increased-risk population and the previous-negative-colonoscopy or no-previous-colonoscopy groups. Multivariate logistic regression was conducted to investigate the risk factors that affect the detection of advanced colorectal neoplasia (ACN) in patients with a positive mSDC2 test. The primary outcome was the PPV for ACN. Results The overall PPVs for ACN, CRC, and colorectal neoplasia were 28.5%, 12.8%, and 44.6%, respectively. The PPV for ACN was higher in the no-previous-colonoscopy group than in the previous-negative-colonoscopy group (30.1% vs 18.5%, P = 0.008) and higher in the increased-risk population than in the average-risk equivalent population (41.1% vs 21.6%, P 0.001). However, the PPV (18.5%) was still high for patients with a previous negative colonoscopy. For ACN detection in patients with a positive mSDC2 test, old age, increased risk, and smoking history were identified as independent risk factors; previous negative colonoscopy was identified as a protective factor. Conclusions The mSDC2 test, which has a high PPV for both ACN and CRC, is expected to be an alternative CRC screening strategy. Patients with a positive mSDC2 test might require a colonoscopy as soon as possible, even if the previous colonoscopy was negative.
Huang et al. (Wed,) studied this question.