Influence of Colorectal Cancer Risk Factors on Predictive Value of a Positive Multitarget Stool DNA Test

Goals: We analyzed if the predictive value of multitarget stool-based DNA (mt-sDNA) varied when patients had pre-existing known colorectal cancer (CRC) risk factors. Background: mt-sDNA test is approved for CRC screening in average-risk patients. Whether patients with a personal history of adenomatous colon polyps or a family history of CRC (CRC risk factors) benefit from mt-sDNA testing is unknown. Study: We reviewed charts for all positive mt-sDNA referrals between 2017 and 2021. Diagnostic colonoscopy adherence rates were calculated. In those who had colonoscopy, we compared detection rates for any colorectal neoplasia (CRN), multiple (3 or more) adenomas, sessile serrated polyps (SSP), advanced CRN, and CRC between patients with and without known CRC risk factors. Results: Of 1297 referrals for positive mt-sDNA, 1176 (91%) completed a diagnostic colonoscopy. The absence of neoplasia was noted in 27% of colonoscopy exams. When neoplasia was identified, findings were as follows: any CRN (73%), multiple adenomas (34%), SSP (23%), advanced CRN (33%), and CRC (2.5%). One or more CRC risk factors were present in 229 (19%) of cases. In the CRC risk factor subgroup, patients having a prior history of adenomatous polyps or a family history of CRC were no more likely to have any CRN, multiple adenomas, SSP, advanced CRN, or CRC compared to average-risk patients when mt-sDNA was positive. Conclusions: In this real-world analysis of positive mt-sDNA referrals, adherence to subsequent diagnostic colonoscopy recommendations was high. The presence of pre-existing CRC risk factors did not affect the positive predictive value of mt-sDNA.