A stool DNA-based SDC2 methylation test for the early detection of colorectal cancer in a symptomatic, high-risk population: A multicenter prospective randomized trial.

OBJECTIVES: Noninvasive stool DNA-based methylation testing has emerged as an effective strategy for the early colorectal cancer (CRC) detection. Syndecan 2 ( SDC2 ) methylation frequently occurs in all stages of CRC; therefore, this study aimed to evaluate the clinical performance of a stool DNA-based SDC2 methylation test for detecting CRC in asymptomatic or high-risk CRC populations. DESIGN: This multicenter prospective study was conducted to determine the clinical performance of the SDC2 methylation test on stool DNA using real-time polymerase chain reaction. Stool samples were collected from asymptomatic individuals prior to colonoscopy, and the test results were independently analyzed via comparison with colonoscopic findings and pathological outcomes as reference standards. RESULTS: Of the 1,124 evaluable participants, 20 had CRC, 73 had advanced adenomatous (AA) polyps (≥1.0 cm), 469 had nonadvanced adenomatous (NAA) polyps (<1.0 cm), 178 had nonneoplastic polyps (NNP), and 384 had negative colonoscopy results. The stool SDC2 methylation test had a sensitivity and specificity of 95.0% and 81.5%, respectively, for detecting CRC, while the sensitivity for detecting AA polyps and CRC was 58.1%. The rate of adenoma detection increased with polyp size ( P <0.01), and sensitivity was not associated with CRC stage ( P =0.864). CONCLUSION: The stool DNA-based SDC2 methylation test attained a high sensitivity for CRC detection in an asymptomatic high-risk population. Further large-scale clinical studies are required to validate the clinical utility of this test as a population-based CRC screening tool. Trial registration: The study protocol (NCT04304131) was registered at ClinicalTrials.gov on March 11, 2020.