Stool-based methylated syndecan-2 testing has a high positive predictive value in an average/increased-risk population: a multicenter retrospective study
Xinxin Huang, Song Zhang, Yanmei Liu, Xiangyu Sui, Peng Pan, Youdong Zhao, Qiwen Fang, Yongjiang Cai, Yuesheng Gong, Wang Li, Haibo Lan, Yunting Deng, Yijin Xu, Zhen Cai, Huiting Chen, Shaoyu Huang, Qianchi Zhou, Zhanmei Huang, Bo Feng, Yinhui Li, Weiguo Yin, Zhaoshen Li, Xiaosheng He, Shengbing Zhao, Yu BaiAbstract
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.