Assessment of Stool DNA Markers to Detect Colorectal Neoplasia in Patients with Inflammatory Bowel Disease: A Multi-site Case-control Study.

Abstract

The FDA-approved multitarget stool-DNA (mt-sDNA) test is a successful colorectal cancer (CRC) screening tool in average-risk individuals but is not indicated for patients with inflammatory bowel disease (IBD). We determined the performance of the mt-sDNA assay without the hemoglobin component (mt-sDNA Hgb-) in patients with IBD, while measuring sensitivity for colorectal cancer and advanced colorectal neoplasia (ACRN). This was a multi-center, proof-of-concept investigation in persons aged 18-84 years with a diagnosis of IBD, or primary sclerosing cholangitis (PSC) with IBD. Enrollment occurred between March 2013-May 2016. Stool was tested with the mt-sDNA molecular markers only, minus the immunochemical hemoglobin component. The analysis set contained 355 samples. The median age was 52 (range 39-62) years, 45.6% female, 93% White. Two-thirds (63%) had ulcerative colitis (UC) and 10.1% had PSC/IBD. Colonoscopy revealed cancer in 8.5% (N=30), advanced precancerous lesions (APLs) in 9.3% (N=33), non-advanced precancerous lesions in 7.6% (N=27), and three-fourths (74.7%, N=265) had negative findings. Mt-sDNA Hgb- sensitivity was 73.3% for any stage cancers, and 76.2% for ACRN. Sensitivity was highest for IBD-associated HGD at 100% and 84.6% for IBD-associated LGD ≥ 1cm. The test showed higher sensitivity and lower specificity in UC than in Crohn's disease. Increasing inflammation score was associated with a significant decrease in mt-sDNA Hgb- test score (p=0.028) amongst neoplasia-negative individuals, but not in patients with ACRN. These data highlight the potential of multitarget stool-DNA marker testing as an important addition to colorectal cancer surveillance by complementing colonoscopic evaluations in inflammatory bowel disease patients.