Clinical significance of a "false positive" stool multi-target DNA test.

803 Background: It has been suggested with limited data that a "false positive" result on a stool multi-target DNA (mtDNA) test is not clinically significant and warrants no further diagnostic evaluation. We aimed to compare the incidence of non-colorectal aerodigestive malignancies in patients who had a false positive versus negative result by stool mtDNA. Methods: All patients who underwent colorectal cancer screening by mtDNA at our institution from 2014 to 2024 were identified. Patients with a positive result who did not have a colonoscopy and those who had a true positive finding (colorectal cancer or advanced precancerous polyp) were excluded. We compared baseline demographics, incidence of aerodigestive cancers, and cancer free survival (CFS) in those who had a negative result versus those who had a false positive result. Results: We identified 48,919 patients who had stool mtDNA testing, 3,352 (6.9%) of whom had a false positive result and 45,567 (93.1%) of whom had a negative result. The median follow-up was slightly longer for the false positive group at 36.0 months (interquartile range 18.0-58.0 months) versus 33.0 months (interquartile range 16.0-51.0 months) for the negative group. Patients with a false positive result had a statistically-significantly higher incidence of aerodigestive cancer than those with a negative result (4.3% vs 1.5%, p