The Utility of Multitarget Stool DNA Testing in Community-Based Clinical Practice

INTRODUCTION: Multitarget stool DNA (MT-sDNA) tests (i.e., Cologuard) serve as screening tests for colorectal cancer (CRC) and are recommended by the US Preventive Services Task Force every 1-3 years. In this study, in a primary care setting, our aim was to evaluate the diagnostic performance of MT-sDNA testing and colonoscopy findings after a positive MT-sDNA testing result. METHODS: This was a retrospective cohort study of electronic health record data including all patients who underwent MT-sDNA tests (Cologuard; Exact Sciences, Madison, WI) at 35 network primary care facilities from Winter of 2019 to Spring of 2023. Patients who were at high risk and had a prior colonoscopy or prior negative MT-sDNA test result were excluded. Assessment of pathology was as previously described, including for advanced adenomas and CRC. RESULTS: Among the 5,827 patients for whom MT-sDNA testing was ordered, 3,119 patients completed the test; 482 (15%) had a positive MT-sDNA test, most of whom were women, had an average age of 65 years, and were predominantly White (Supplemental Figure 1, Table 1). Among these 482 patients, 277 (57%) had a follow-up screening colonoscopy, with 253 patients having complete colonoscopy data. Ten patients (4%) had CRC, 61 (24%) had advanced adenomas, and 184 patients (73%) had neither. The sigmoid colon was the most common site for CRC, with 8 of 10 patients having tumor, node, metastasis stage ≥1 CRC. DISCUSSION: The rate of colon cancer detection (10/5,827 [0.2%] patients for whom it was ordered and 10/3,119 [0.3%] who completed the test) was lower than expected in a screening cohort. Most patients who completed MT-sDNA testing had a false-positive result for advanced adenomas or CRC (73%). Together, these findings raise questions about the effectiveness of screening based on MT-sDNA testing in an average risk population.