Cologuard: A New Test For Reducing The Risk Of Colon Cancer

Issue 25 Summer/Fall 2015

Colorectal cancer (CRC) is the second most common cancer affecting men and women. Fortunately, though, it is highly preventable if individuals over age 50 undergo screening.

There are several CRC screening tests from which to choose. Non-invasive tests analyze a stool sample for occult blood, which include the so-called fecal occult blood test (FOBT) and fecal immunochemical test (FIT). Other tests employ structural imaging of the colon by endoscopy (colonoscopy, sigmoidoscopy). Both of these have been shown to reduce deaths from CRC. But with choice comes some confusion as to which test to do.

Cologuard noninvasive stool DNA screening test kit.

Over the past decade, colonoscopy and FIT have become the most widely used. Colonoscopy is often considered the best test because: (1) it can both detect and remove cancerous and precancerous polyps; (2) it misses very few cancers or polyps; (3) if normal, it does not have be repeated for 10 years (sooner if polyps are found), and (4) it is covered by most insurances.

No wonder colonoscopy is often preferred by many physicians and patients. But, colonoscopy also has limitations: (1) the skill of the endoscopist; (2) adequate bowel cleansing; (3) time off from work/caretaking; (4) a rare but finite risk of serious complications, such as bowel perforation or bleeding; (5) the need for an escort because sedation is often used; and (6) the high cost for patients with high deductibles or no insurance.

Ideally, a cancer screening test should be non-invasive, easy to perform, safe, operator- independent, inexpensive, and accurate. FIT testing has most of these advantages. It is non-invasive, performed at home on a single stool sample, inexpensive, and operator-independent. However, FIT is known to miss up to 30% of cancers and 70-80% of the most precancerous polyps because bleeding rates may be low.

As such, FIT should be repeated every year, something that most patients (and their physicians) find hard to do, or keep track of. Even when this is done, the nature of bleeding by colon cancers and polyps is such that those located in the distal colon (close to the rectum) are detected better than those in the proximal colon (further in from the rectum). Moreover, false-positives occur if there is blood in the stool for some reason besides a cancer/polyp.

Enter Cologuard®: a new non-invasive stool-based CRC screening test. Cologuard ® analyzes stool for occult blood, but also detects abnormal DNA that is shed from the cells lining the colon, especially polyps and cancers which have higher rates of cell shedding.

A recent multicenter study performed throughout the United States included approximately 10,000 healthy individuals age 50 and older who performed FIT and Cologuard® on the same stool sample prior to cleansing their bowel for colonoscopy.

The Cologuard® results were compared to FIT results, using the colonoscopy findings as the gold standard. Cologuard® detected 92% of CRC compared to 74% with FIT.

Colon cancer and polyp

Most of the advantage of Cologuard® was in better detection of early stage CRCs – lesions that are often curable by surgery alone without the need for chemotherapy. In addition, Cologuard® outperformed FIT for finding more polyps overall, more of the “worst” polyps (those larger than 2 cm in size, those with high grade dysplasia, and sessile serrated polyps), and more cancers and polyps in the proximal colon.

However, there were more false-positive test results with Cologuard® than with FIT – about 5% of individuals with a normal colonoscopy had a positive FIT test, compared to 10-11% with Cologuard®. This means that Cologuard® may send more people to colonoscopy, a test which is recommended anyway by most authorities. A 3- year interval is recommended for Cologuard®.

The current cost of the test is approximately $600 with CMS paying approximately $500. Private insurers will soon decide whether to cover Cologuard®.

Cologuard® is done in the privacy of the patient’s own home using a single stool sample without the need to limit one’s diet or cleanse the bowel. The collection kit contains a preservative solution that avoids the need to freeze the specimen.

Once a clinician orders a Cologuard® test, a central patient navigation center (operating 24/7; supporting 70 languages) reaches out to the patient and assists them through the process, ensuring high levels of patient adherence and successful test completion.

The test is returned directly to a central lab using a pre-paid mailing container that the company provides. The report is then sent to the provider who ordered the test.

Presently, CRC screening rates are approximately 65-68%. The American Cancer Society and the Centers for Disease Control have set a national goal to reach “80% by 2018” for CRC screening by any available method. Cologuard® represents an important advance for non-invasive CRC screening that can help us get there.

Steven H. Itzkowitz, MD

Steven H. Itzkowitz, MD
Professor of Medicine and Oncological Sciences
The Dr. Henry D. Janowitz Division of Gastroenterology
Icahn School of Medicine at Mount Sinai
New York, NY