Lingering Questions

Overall, though, the researchers concluded that further evaluation is needed.

In an accompanying editorial, Douglas J. Robertson, MD, MPH, of the White River Junction Veterans Affairs Medical Center in Vermont and Geisel School of Medicine at Dartmouth in Hanover, NH, and Jason A. Dominitz, MD, MHS, of the VA Puget Sound Health Care System, University of Washington School of Medicine in Seattle, expressed several concerns.


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In particular, Drs. Robertson and Dominitz noted that the study only compared the one-time sensitivity of the tests, leaving the question of how often the DNA test should be repeated unanswered. Because DNA testing is more expensive, they wrote, it’s unlikely that screening would be performed annually in the way that FIT is.2

Furthermore, they pointed out that repeated FIT screening improves neoplasia detection and therefore long-term data over a defined interval would be necessary for a more accurate comparison between FIT and DNA testing.

Finally, Drs. Robertson and Dominitz cited the higher false-positive rate as a major issue. False-positive results could lead to earlier repeat colonoscopies and unnecessary extracolonic work-up.

However, more data may help mitigate these concerns, they wrote, explaining that the stool DNA test is “clearly an improvement over its predecessors.”

RELATED: Lifestyle Factors Before CRC Diagnosis May Affect Survival

“Comparative-effectiveness studies are now needed to clarify the role of stool DNA testing with respect to programmatic screening with other test options,” Drs. Robertson and Dominitz wrote.

“Only through a better understanding of other key factors, such as the screening interval, adherence, cost, and diagnostic evaluation of positive results, can we determine the appropriate place for stool DNA testing on the screening menu.”

From the FDA

From March 26 to 27 of this year, the US Food and Drug Administration’s (FDA) Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee met to discuss whether the benefits of the Cologuard stool DNA test outweigh its risks. The 10-member panel thought so and voted in favor of approving the test.

In an article from HealthDay, Frank Sinicrope, MD, professor of medicine and oncology at the Mayo Clinic in Rochester, MN, said the study results suggest that stool DNA testing is superior to FIT for CRC screening. One significant advantage involves its efficacy in detecting advanced precancerous lesions, he noted.3


Expert Opinion
Richard M. Goldberg, MD
Richard M. Goldberg, MD

What the researchers found was that the DNA test, coupled with the hemoglobin test, was more sensitive and more specific compared with the FIT. However, the DNA test also yielded more false-positives. Specifically, the data showed that about 732 of 1,611 positive tests for DNA testing turned out to be false-positives, which is a substantial amount compared with the 248 of 696 with FIT.

Another interesting aspect of this type of technology is that it could potentially detect cancers not just in the colon but in other areas of the digestive tract. We spit up and swallow phlegm from our lungs and throat constantly, so that DNA ends up in our gastrointestinal tract. So another question for the future is could this test be used to screen for more than just colon cancer?

Overall, this study demonstrates an exciting application of molecular genetics to screening. Hopefully, it is one of many future studies that will help us apply it in a way that will positively influence clinical outcomes for people… Read more

Richard M. Goldberg, MD
Physician-in-Chief
James Cancer Hospital
Professor of Medicine
The James Comprehensive Cancer Center at Ohio State University
Columbus, OH

References

  1. Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014 Mar 19. [Epub ahead of print]; doi:10.1056/NEJMoa1311194.
  2. Robertson DJ, Dominitz JA. Stool DNA and colorectal-cancer screening. N Engl J Med. 2014 Mar 19. [Epub ahead of print]; doi:10.1056/NEJMe1400092.
  3. Mozes A. FDA Advisory Panel recommends approval of at-home colon cancer test. HealthDay. March 28, 2014. http://consumer.healthday.com/cancer-information-5/colon-cancer-news-96/new-stool-test-shows-promise-as-colon-cancer-screen-686274.html. Accessed March 31, 2014.