Noninvasive DNA Test for Colorectal Cancer Gets FDA Thumbs-up

Test May Offer Solid Alternative to Current Screening Options, Says FP Expert

August 29, 2014 02:51 pm Chris Crawford

Among cancers that affect both men and women, colorectal cancer is the third most common cancer and the second leading cause of cancer-related death in the United States, according to the CDC. The agency estimates that if everyone age 50 or older participated in recommended colorectal cancer screening(www.cdc.gov), at least 60 percent of colorectal cancer deaths could be avoided.

Now, family physicians and other clinicians have a singular new option for detecting this life-threatening condition. Moreover, CMS has already laid the groundwork for Medicare coverage for the test.

On Aug. 11, the FDA approved Cologuard, a stool-based colorectal screening test that detects red blood cells and DNA mutations that can indicate the presence of abnormal, possibly precancerous growths, according to an FDA news release(www.fda.gov). It is the first fecal DNA test for colorectal cancer to receive the agency's thumbs-up; previous candidates have lacked adequate sensitivity and specificity.

Specifically, Cologuard detects hemoglobin and mutations associated with colorectal cancer in DNA of cells shed by advanced adenomas as stool moves through the large intestine and rectum. Patients who receive a positive test result are advised to undergo a diagnostic colonoscopy.

"This approval offers patients and physicians another option to screen for colorectal cancer," said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health at the FDA's Center for Devices and Radiological Health (CDRH), in the news release. "Fecal blood testing is a well-established screening tool, and the clinical data showed that (Cologuard) detected more cancers than a commonly used fecal occult test."

Story highlights
  • On Aug. 11, the FDA approved Cologuard, a stool-based colorectal cancer screening test that detects red blood cells and DNA mutations; it is the first fecal DNA test for colorectal cancer to receive the agency's thumbs-up.
  • A study published in the New England Journal of Medicine examined the safety and effectiveness of Cologuard, and found that it accurately detected 92 percent of colorectal cancers and 42 percent of advanced adenomas in the clinical trial population.
  • Cologuard is the first product to be reviewed through a joint FDA-CMS pilot program in which the agencies concurrently review certain medical devices to help reduce the time between FDA approval and Medicare coverage.

The FDA's approval of Madison, Wisc.-based Exact Sciences' Cologuard expands the options for colorectal cancer screening but does not change current related guidelines. The U.S. Preventive Services Task Force (USPSTF) does not recommend stool DNA testing as a method to screen for colorectal cancer. The USPSTF's current screening recommendation(www.uspreventiveservicestaskforce.org) for average-risk adults ages 50 to 75 calls for using fecal occult blood testing (FOBT), sigmoidoscopy or colonoscopy.

However, the USPSTF currently is reviewing its colorectal cancer screening recommendations; evaluation of fecal DNA screening was specifically included in the systematic evidence review(www.ncbi.nlm.nih.gov) the task force is using to inform that update.

Cologuard Study

A recent study(www.nejm.org) published in the New England Journal of Medicine examined the safety and effectiveness of Cologuard, screening almost 10,000 asymptomatic participants ages 50 to 84 who were at average risk for colorectal cancer and were scheduled to undergo a screening colonoscopy. The trial compared Cologuard to fecal immunochemical testing (FIT).

Compared with FIT, Cologuard was more accurate in detecting colorectal cancers (92 percent versus 74 percent) and advanced adenomas (42 percent versus 24 percent). It was less accurate than FIT, however, at correctly identifying subjects negative for colorectal cancer or advanced adenomas (87 percent versus 95 percent).

Family physician Richard Wender, M.D., who is chair of the National Colorectal Cancer Roundtable and chief cancer control officer for the American Cancer Society (ACS), told AAFP News he was impressed with the sensitivity of Cologuard in the clinical trial. He added that a precursor to Cologuard had at one time been on an ACS-recommended list of colorectal cancer screening options, but the test is no longer available.

"Cologuard has more robust data than the older stool DNA test and better performance," Wender said, "so a good argument for including the test in guidelines can be made."

CMS Coverage

Cologuard is the first product to be reviewed through a joint FDA-CMS pilot program for parallel review,(www.fda.gov) under which the agencies concurrently review certain premarket medical devices to reduce the time between FDA approval and Medicare coverage.

"Parallel review allows the last part of the FDA process to run at the same time as the CMS process, cutting as many as six months from the time of study initiation to coverage," said Nancy Stade, CDRH's deputy director for policy, in the news release.

CMS proposes to cover the Cologuard test once every three years for asymptomatic individuals ages 50 to 85 who are at average risk of developing colorectal cancer.

"This new process (of parallel review) is a good step in developing a more efficient and streamlined approach to test approval," Wender said. "I applaud the FDA and CMS for developing this innovative process to accelerate the availability of the test.

"I think it is fair to say that having both agencies join in approving the test and paying for the test does constitute additional endorsement of the test."

The Future for Cologuard

For Cologuard to become widely used, it will need to be added to the USPSTF and other major colorectal cancer screening guidelines, Wender said. Otherwise, the test may not be covered by some commercial insurers.

As to Cologuard's limitations, Wender said that although CMS has decided to pay for the test every three years, the ideal testing interval has not yet been determined. Furthermore, at a cost of $500 (the preliminary payment amount established by CMS), the test is likely to be cost-effective but its relative cost-effectiveness compared to other screening options is unclear. Finally, the acceptability of the test to clinicians and patients also is not fully known.

Wender said it's important for physicians to remember that there are already two widely used screening options: colonoscopy every 10 years or FIT every year. He added that high-sensitivity guaiac FOBT and CT colonoscopy are additional options to consider. The variety of options should help the ACS reach its "80% by 2018"(nccrt.org) initiative's goal to have 80 percent of adults ages 50 and older screened for colorectal cancer by 2018.

"In short, we already have both more and less invasive, more and less costly options to screen everyone for colorectal cancer," said Wender. "We can achieve the 80 percent goal using available tests. But it is conceivable that having Cologuard available and approved may place the 80 percent goal more within our reach."


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