Stool DNA testing – a new test for colon cancer screening
Screening for colorectal cancer (CRC) is highly effective in preventing this disease, which is why it has been endorsed by all major-medical societies, receiving a grade “A” recommendation from the United States Preventative Services Task Force (USPSTF). Many screening tests have been endorsed by guideline committees. In practice, however, colonoscopy and fecal occult blood testing are the predominant methods used, particularly colonoscopy.
A new multi-target stool DNA (MT-sDNA) test (Cologuard; Exact Sciences Corporation) goes beyond detecting occult blood in the stool because it also incorporates analysis of abnormal DNA. It would seem impossible that specific human gene mutations could be detected in stool among the enormous amounts of DNA arising from bacteria and food products, which actually compromise 99.99% of stool DNA with only 0.01% representing human DNA! However, thanks to technological advances, analyzing DNA alterations in stool has become a reality. Numerous clinical validation studies have demonstrated proof that stool DNA testing is more sensitive than fecal occult blood testing in detecting adenomas and colon cancer. MT-sDNA was approved by the United States Food and Drug Administration (FDA) on August 11, 2014 for use in general CRC screening. On the same date, the Center for Medicare and Medicaid Services (CMS) ruled that the test would be covered by Medicare at a frequency of every three years up to age 85.
However, numerous practical clinical questions remain:
#1) Is the sensitivity of MT-sDNA high enough to be an effective screening test? With a 93% sensitivity for stage I-III colon cancers, MT-sDNA is similar to that of colonoscopy and significantly higher than the reported 70% sensitivity utilizing fecal occult blood testing with fecal immunochemical test (FIT). Thus, DNA stool testing misses about 7% of colon cancers whereas FIT misses 30%. Likewise, it out performs FIT for detecting those precursor lesions that are most likely to develop into cancer: adenomas larger than 2 cm, those with high-grade dysplasia, and sessile serrated polyps greater than 1 cm. This is understandable knowing that these subtle lesions typically do not bleed.
#2) Will patients accept this test? Because this is a new test in clinical practice, there is limited data on patient acceptance. However, previous prospective surveys revealed that DNA stool testing received the same or higher mean rating than guaiac-based FOBT.
#3) How often should MT-sDNA be performed? Again, because this is a new test, there has not been enough time to do a study which would offer guidance regarding screening interval. CMS, however, has recommended a 3-year interval based on modeling studies.
#4) Isn’t this test too expensive? At present, the list price is $649 (Medicare costs $509). However, this price includes a national 24-hour, 7 days a week, patient navigation and compliant service. Also, if the test is done every 3 years, the cost can be amortized to approximately $216 per year.
#5) Should this test be used in high-risk patients? The simple answer is NO. The currently available test was designed for, and tested only in, average risk, asymptomatic individuals. High risk patients such as those with inflammatory bowel disease, positive first-degree family history of CRC affecting the family member under the age of 60, hereditary cancer syndromes such as Lynch Syndrome and those with previous colon cancer or adenomas should receive colonoscopic screening.
#6) Should this test replace colonoscopy for screening? There is not enough evidence at present to suggest DNA/FIT stool testing replace colonoscopy for CRC screening in the average risk patient. Colonoscopy remains the gold standard. It not only is highly sensitive and specific at detecting CRC and smaller, flat lesions such as sessile serrated polyps, but also offers the opportunity for biopsy and/or polypectomy at a single setting. Furthermore, the screening interval of 10 years with colonoscopy compared to the present recommended 3 year interval for MT-sDNA surveillance and yearly interval for FIT, could improve patient compliance potentially resulting in decreasing the risk of developing interval colon cancer.
#7) Which patient would benefit most from DNA stool screening? It would be very reasonable to offer this test to individuals who absolutely refused to have a colonoscopy or due to their elderly age or medical comorbidities are not good candidates for colonoscopy and/or sedation. However, it is important to discuss with the patient prior to obtaining a MT-sDNA study that if the results are positive they will require a colonoscopy.