Multi-Target Stool DNA Test: A New High Bar for Noninvasive Screening

Abstract

Stool DNA testing has evolved into what is now a highly accurate and well-validated test for the screen detection of colorectal neoplasia. An optimized and automated multi-target stool DNA test (MT-sDNA) has achieved the same high point-sensitivities as reported for colonoscopy and significantly higher sensitivity than by fecal immunochemical blood testing for detection of early-stage cancer and advanced precancer. Thus, MT-sDNA sets a new high criterion standard for the noninvasive screen detection of colorectal neoplasia. With clinical application, MT-sDNA has potential to meaningfully address current gaps in our approach to CRC screening through benefits of its high accuracy on screening effectiveness, user-friendly features on patient compliance, and easy mail-out distribution on test access. The US Food and Drug Administration and Center for Medicaid and Medicare Services have recently completed their parallel reviews of MT-sDNA, which has just become available for clinical use. This review summarizes the recent clinical validation data on MT-sDNA, addresses central clinical questions at this front end of implementation, and touches on innovative future applications of stool DNA testing.

Molecular markers for colorectal cancer screening

“…Within this screening model, the false positive rate per year of MT-sDNA is comparable to or lower than that of FIT. 91 Until further data become available on the diagnostic yield of follow-up colonoscopy and upper GI interrogation in patients who are initially MT-sDNA positive but colonoscopy negative, clinical judgment will be required.…”

“…False positive results lead to unnecessary, and costly, further evaluation. While the screening interval for MT-sDNA testing has yet to be fully defined, current models predict 3 year screening intervals 91 and CMS has approved coverage for this screening frequency. At a 3 year screening interval, the programmatic specificity of MT-sDNA (false positive rate of 3-4% per year) would be equal to or higher than that of FIT performed annually (false positive rate of 4-5% per year), as mentioned above.…”

Fecal occult blood versus DNA testing: indirect comparison in a colorectal cancer screening population

“…In this study, which was sponsored by the manufacturer of the MSDT and which employed intentional oversampling of older adults ≥65 years of age, MSDT detected significantly more cancers but had more false-positive results than the FIT (sensitivity 92.3% versus 73.8%, specificity 86.6% versus 94.9%). This MSDT whose costs exceed the costs of FITs ~20-fold8 and which requires substantially more complex logistics for stool sampling (collection of a whole bowel movement) has been claimed to be the new high bar benchmark for noninvasive CRC screening 9. The test is commercially available as Cologuard™ and increasingly used for CRC screening after Food and Drug Administration (FDA) approval in August 2014 and start of Medicare coverage in October 2014.…”

Screening for Hepatocellular Carcinoma and Cholangiocarcinoma: Can Biomarkers Replace Imaging?

“…The need for implementing invasive techniques to acquire bile has been a fundamental limitation to the clinical use of bile biomarkers as surveillance for CCA. However, with the availability of the recently approved multi-target stool DNA testing system (Cologuard®) for screening for colorectal polyps and cancer, it is now possible to imagine the potential addition of novel aerodigestive cancer site specific assays to a stool DNA-based test, leading to further population-based bile duct cancer detection in a much more feasible and non-invasive fashion 89 .…”