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<0.001), including head and neck (0.6% vs 0.4%, p=0.018), lung (1.5% vs 0.5%, p<0.001), and non-colorectal gastrointestinal malignancies (2.2% vs 0.6%, p<0.001) (Table). Patients with a false positive result also had a shorter cancer free survival than those with a negative result (mean 75.6 months, 95% CI 74.9-76.3 v 85.0 months, 95% CI 84.5-85.3; p<0.001; median not reached for either group). When controlling for demographic variables that were different between the two groups, false positive stool mtDNA was an independent predictor of cancer free survival (HR 1.49, 95% CI 1.23-1.72). Conclusions: These data suggest that a false positive finding on a stool mtDNA test is clinically relevant and does warrant further diagnostic work-up, potentially with upper endoscopy and/or cross-sectional imaging. Incidence of non-colorectal aerodigestive cancers in patients with false positive vs negative mt-sDNA. Aerodigestive Cancer Type False Positive (N=3,352) Negative (N=45,567) P Head and Neck 21 (0.63%) 166 (0.36%) 0.021 Lung 50 (1.49%) 227 (0.50%) <0.001 Non-colorectal GI 74 (2.21%) 276 (0.61%) <0.001 Total 145 (4.32%) 669 (1.47%) <0.001
Aragon et al. (Sat,) studied this question.