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

Background and Aims 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 haemoglobin component [mt-sDNA(Hgb-]) in patients with IBD, while measuring sensitivity for colorectal cancer and advanced colorectal neoplasia [ACRN]. Methods This was a multi-centre, proof-of-concept investigation in persons aged 18-84 years with a diagnosis of IBD, or primary sclerosing cholangitis [PSC] with IBD. Enrolment occurred between March 2013 and May 2016. Stool was tested with the mt-sDNA molecular markers only, minus the immunochemical haemoglobin component. Results The analysis set contained 355 samples. The median age was 52 [range 39-62] years, 45.6% were female and 93% were 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] and non-advanced precancerous lesions in 7.6% [N = 27], and three-quarters [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 high-grade dysplasia at 100% and 84.6% for IBD-associated low-grade dysplasia >= 1 cm. 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 [ = 0.028] amongst neoplasia-negative individuals, but not in patients with ACRN. Conclusions These data highlight the potential of multitarget stool-DNA marker testing as an important addition to colorectal cancer surveillance by complementing colonoscopic evaluations in IBD patients.