Cologuard vs. Colonoscopy

Colon cancer screening is a strategy used to identify the possible presence of an as-yet-undiagnosed colon cancer or pre-cancer in individuals without signs or symptoms. Screening can be done by stool based tests (which detect blood or altered DNA, or both) or direct visualization tests, such as colonoscopy. The diagnostic performance of stool based tests is measured in comparison to what a colonoscopy would have shown, in other words, colonoscopy is the ‘gold-standard’.  It is of course much better to find ‘pre-cancer’ than cancer. We need to keep this in mind for our discussion.

What stool tests are available for colon cancer screening?

Currently available stool based tests are guaiac-based Fecal Occult Blood Test (gFOBT) that detect invisible blood in stool by a simple chemical reaction, and immunochemical Fecal Occult Blood Test (iFOBT, FIT) that use antibodies to detect human hemoglobin protein in stool. More here.

For years there has been an interest in developing a useful stool test that would work by detecting abnormal DNA from cancer or precancer in the colon. This was only partially successful. To make a workable screening test, molecular analysis (DNA testing) had to be combined with the detection of blood by immunochemical tests (FIT) [1]. Therefore, these stool tests are known as Multitarget Stool DNA (MT-sDNA) testing. The only commercial product in this category is Cologuard™, FDA approved for  screening of asymptomatic persons at average risk for colorectal cancer.

Cologuard™ combines FIT and DNA testing.

How does Cologuard™ compare with colonoscopy?

In a large multicenter study [2] with almost 10,000 participants Cologuard was compared with an immunochemical Fecal Occult Blood Test (FIT), colonoscopy serving as a gold standard. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT. For ‘pre-cancer’ the results were not so good:  The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT. But it is ‘pre-cancer’ that we should be after!

An interesting metric is the number needed to screen. The lower the number the better the test. This is a table from the publication:

Numbers of Persons Who Would Need to Be Screened with Colonoscopy, Multitarget DNA Test, and FIT to Detect One Colorectal Cancer and One Advanced Precancerous Lesion.
Finding Number Needed to Screen (95% CI)
Colonoscopy Multitarget DNA Test FIT
Any colorectal cancer 154 (120–200) 166 (130–217) 208 (156–286)
Stage I to III colorectal cancer 166 (130–217) 178 (140–238) 227 (169–313)
Advanced precancerous lesion 13 (12–14) 31 (28–35) 55 (48–65)

Based on this data, colonoscopy is 2.4 times better in detecting ‘advanced precancerous lesions’ than the Multitarget DNA Test and 4.2 times better than FIT.

Where does Cologuard™ FIT in?

Cologuard™ represents a significant advance in stool based colon cancer screening over FIT but still has low sensitivity in finding advanced precancerous lesions.

However, some average risk patients who would otherwise never have a screening colonoscopy will have few excuses not to use Cologuard™, it only needs to be done once (as opposed to three times for gFOBT), is non-invasive, doesn’t require any dietary restrictions and has the best performance characteristics of all stool based tests. A major disadvantage is high cost but insurance coverage is increasing. If Cologuard™ is positive, a colonoscopy is needed. Cologuard™ should therefore not be prescribed for patients who would – under no circumstances – have a colonoscopy.

If you think Cologuard™ is something you may want to consider schedule a consultation with Dr. Gottlieb at the Templeton or San Luis Obispo office.

[1] The MT-sDNA test (now Cologuard) uses quantitative allele-specific real-time target and signal amplification assays for aberrant methylation of the BMP3 and NDRG4 gene promoter regions, for KRAS gene mutations, and for quantification of β-actin (a reference gene for human DNA quantity) as well as an immunochemical assay for human hemoglobin. Quantitative measurements of each marker are incorporated into a validated logistic regression algorithm, with a prespecified cutoff to indicate test positivity.

[2] Imperiale TF, Ransohoff DF, Itzkowitz SH, Levin TR, Lavin P, Lidgard GP, Ahlquist DA, Berger BM. Multitarget stool DNA testing for colorectal-cancer screening. New England Journal of Medicine. 2014 Apr 3;370(14):1287-97.

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