The multi-target stool DNA test reaches patients

Historical milestone — this page describes an event dated 2014. It is not current breaking news.

What was approved

On August 11, 2014, the FDA approved Cologuard, a stool test made by Exact Sciences. Its premarket approval number is P130017.

It was the first screening test to look in stool for DNA changes shed by colorectal tumors, not just for hidden blood. A person collects a sample at home and mails it to a laboratory.

The approval letter is precise about the limits. Cologuard was indicated to screen adults aged 50 or older at typical average risk. A positive result should be followed by diagnostic colonoscopy. And the FDA stated that Cologuard is not a replacement for diagnostic colonoscopy, or for surveillance colonoscopy in high-risk people.

What the test actually looks for

The DNA test bundles several measurements into one result.

It runs molecular assays for KRAS mutations. It also checks for abnormal methylation of two genes called NDRG4 and BMP3, plus beta-actin as a reference. Methylation is a chemical tag on DNA that switches genes off, and tumors often place those tags in the wrong places.

Alongside that, it runs an immunoassay for hemoglobin, which is the same thing a fecal immunochemical test measures.

A logistic-regression algorithm combines these into one score. In the pivotal study, a score of 183 or more counted as positive.

The trial that supported it

The evidence came from a study of 9,989 people at average risk who could be evaluated. Everyone had both the stool DNA test and a fecal immunochemical test. Everyone then had a colonoscopy, which settled what was really there.

Sixty-five participants, 0.7%, had colorectal cancer. Another 757, or 7.6%, had advanced precancerous lesions.

The DNA test found 92.3% of the cancers. The fecal immunochemical test found 73.8%.

For advanced precancerous lesions, the gap was wider in relative terms: 42.4% against 23.8%. For large sessile serrated polyps of 1 centimeter or more, it was 42.4% against 5.1%.

The trade-off, stated plainly

Better detection came with more false alarms.

Among participants whose colonoscopy showed nothing advanced, specificity was 86.6% for the DNA test. It was 94.9% for the fecal immunochemical test. Among those with a completely clear colonoscopy, the figures were 89.8% against 96.4%.

Put the other way round, about one in ten people with a clean colon got a positive DNA result anyway. Each of those needs a colonoscopy to sort out, with its preparation, sedation, and small procedural risk.

The study also reported how many people would need screening to find one cancer: 154 with colonoscopy, 166 with the DNA test, and 208 with the fecal immunochemical test.

Where it sits today

NCI now lists multitarget stool DNA testing, shortened to sDNA-FIT, as one of several approved options. It detects hemoglobin along with DNA markers. Those markers come from cells shed by the lining of the colon and rectum.

NCI notes that experts generally suggest repeating it at least every three years. A fecal immunochemical test alone is generally advised every year or two, and colonoscopy every ten years.

A positive stool test of any kind leads to the same next step. NCI is explicit: people with a positive finding are advised to have a colonoscopy.

When to get checked

NCI reports that most expert groups now advise screening at average risk from age 45, continuing to 75. That includes the US Preventive Services Task Force. Between 76 and 85, the decision depends on life expectancy, other health conditions, and past screening.

Some people are advised to start earlier and screen more often. That includes people with inherited conditions such as Lynch syndrome or familial adenomatous polyposis. It also includes a family history of colorectal cancer, a personal history of advanced polyps, or inflammatory bowel disease.

Screening is for people without symptoms. Symptoms need their own visit, whatever the screening schedule says. NCI lists blood in the stool, a change in bowel habits, and a feeling that the bowel does not empty. It also lists narrower stools, persistent gas pains or cramps, unexplained weight loss, fatigue, and vomiting.

Our page on colorectal cancer screening compares the tests, and our overview of colorectal cancer covers what happens after a positive result.

What this story cannot tell you

The 2014 study measured how well the test detects cancer that colonoscopy also found. It did not measure whether people screened this way live longer. That would take a much longer trial.

It also cannot say which test is right for one person. A test done reliably at home beats a better test that never gets booked. The reverse is also true.

Finally, the FDA said plainly that this test does not replace surveillance colonoscopy for people at high risk. And a negative stool test is a snapshot, not a guarantee. That is why the interval matters as much as the result.

Sources

• FDA summary of safety and effectiveness data, Cologuard, PMA P130017
• Imperiale TF et al., Multitarget stool DNA testing for colorectal-cancer screening, N Engl J Med 2014 (NCBI E-utilities record)
• NCI: Screening Tests to Detect Colorectal Cancer and Polyps
• NCI PDQ: Colon Cancer Treatment (Patient Version)

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

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