Mark A. Bishara, MD

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Can Cologuard Improve Colon Cancer Screening Rates?

By http://www.markbisharamd.com/author/
September 17, 2014

At the Office of Dr. Bishara and The Paragon Plastic Surgery & med Spa, we want our male patients to be educated about their health too. In a recent article in MedScape, Dr. David Johnson discusses new breakthroughs in screening for colon cancer

WHERE WE'RE AT WITH SCREENING

Hello. I am Dr. David Johnson, Professor of Medicine and Chief of Gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

Cologuard®, a stool DNA test manufactured by Exact Sciences (Madison, Wisconsin) has just been approved by the US Food and Drug Administration (FDA). It has received a tremendous amount of attention in the lay press, and recently the pivotal study analyses were published in the New England Journal of Medicine.[1] I will give you an overview of how this test might play out in clinical practice for gastroenterologists, primary care providers, other healthcare providers, and patients.

We are doing better with colon cancer screening, but we still are missing 35%-40% of patients who are eligible for healthcare screening. We have seen a tremendous increase in screening over the past decade, but in the past 3 years, this has leveled off to 60%-62%, and the rate of rise in screening has plateaued.[2] The Centers for Disease Control and Prevention (CDC) set their target for colon cancer screening at 80% by 2018, but the current rate of 62% has been holding for the past 3 years. We have seen a 46% reduction in colon cancer-related deaths over the past decade, primarily from the emphasis on colon cancer screening, but nonetheless, screening rates are flat and we are not making progress. What is the problem?

Colonoscopy is the gold standard for screening, but some patients are resistant to having a colonoscopy for many reasons: the "prep," and taking a day off work, for example.

When the US Preventive Services Task Force (USPSTF) published colon cancer screening recommendations in 2008,[3] few options were available beyond flexible sigmoidoscopy, fecal occult blood testing, and colonoscopy -- the only screening methods that met evidence-based standards. At that time, the USPSTF did not accept CT colonography or even the stool DNA test as screening options, because in 2004, the sensitivity of the stool DNA test was only marginally better than 50% for the detection of colon cancer.[4] It was better than the fecal occult blood test by a margin of 4, and it was not very good at all for detecting advanced adenomas.

THE MULTITARGETED APPROACH TO SCREENING

Fast-forwarding to the present technology, the Cologuard is a new and revised stool DNA test. It detects aberrant methylation markers on 2 promoter genes (BPM3 andNDRG4) as well as KRAS mutations, and beta-actin, which is a reference gene for human DNA quantity. In addition to those 4 biomarkers, Cologuard includes a fecal immunohistochemical test (FIT). This is the Polymedco test, and it is set at 100 ng of hemoglobin per mL of buffer. This is the standard threshold used in screening trials for FIT, and it was added to increase the sensitivity of detection of colon cancer.

Approximately 10,000 patients were enrolled in the pivotal study, all of whom had not had recent screenings for at least 9 years for colonoscopy or 5 years for CT colonography or barium enema. These patients were evaluated with colonoscopy and with FIT as well as the combination Cologuard test. The background prevalence of colon cancer in the study was 0.7%. Advanced adenomas were defined as adenomas with high-grade dysplasia, adenomas with 25% or more villous component, or sessile serrated polyps 1 cm or larger in size. With this new twist on advanced lesions, the background prevalence for advanced adenomas was 7.6%.

HIGHEST SENSITIVITY OF STOOL-BASED TESTS

The sensitivity of Cologuard for detection of colorectal cancer was 92.3% compared with 73.8% for FIT alone.

For detection of advanced adenomas, the sensitivity of Cologuard was 42.4%, and for FIT alone it was 23.8%. Fecal testing has not been very sensitive for the detection of advanced adenoma, but with Cologuard, we are seeing nearly a doubling of sensitivity with stool DNA, a big upswing in advances in stool-based testing. For the detection of high-grade dysplasia, the Cologuard had a sensitivity of 69.2% vs. 46.2% for FIT alone. For sessile serrated polyps, the sensitivity was 42.1% for stool DNA testing and 5.1% for FIT, a huge margin of difference.

Of interest, the stool DNA test did not vary by disease stage (that is, it was as good for stage 1 disease as it was for stage 4 disease) or by location. Fecal occult blood testing was always more sensitive for distal lesions, but that is not the case with stool DNA testing. FIT sensitivity catches up in later stages of disease, becoming equal to stool DNA in stage 3 and 4 disease. Stool DNA is more sensitive for advanced adenomas, especially for more distal lesions -- sensitivity was 54.5% (distal) vs 48.9% (proximal) -- and for larger lesions.

PUTTING COLOGUARD INTO PRACTICE

As we put this into perspective, there are a couple of caveats.

One is that we don't know what the test performance characteristics will be when this is ultimately rolled out and used in practice. In 6.4% of patients who had the stool DNA test, for whatever reason the samples couldn't be analyzed. In the context of the baseline prevalence of colon cancer in this population, that means that they lost the results for 689 patients, and 4 cancers could have been missed just because the test could not be done. That can change the statistics a little bit. The number needed to screen to detect 1 cancer is 154 for colonoscopy; for the stool DNA/Cologuard test, it is 166; and for FIT, it is 208.

The recommendation from the multisociety task force and the American College of Gastroenterology guidelines[5] is that if stool DNA testing is used, it should be done at 3-year intervals.

Patients should not view this as an alternative to colonoscopy, and it should be offered to patients only after they have explicit guidance that colonoscopy is the best test that we have for prevention because we can identify more precancerous polyps than we can with any stool-based testing. A colonoscopy needs to be done by a quality colonoscopist. Detection rates will vary on the basis of the adenoma detection rate of the individual colonoscopist, so the better we can define our adenoma detection rates, the better patients can select a colonoscopist by asking, "What is your adenoma detection rate?"

ALTERNATIVE TO COLONOSCOPY, NOT A REPLACEMENT

Will Cologuard become a replacement for colonoscopy? No. It is a test that should be offered to patients who refuse colonoscopy. It will still be an expensive test -- the estimated cost is $590. It is money well spent if it brings the people who refuse colonoscopy into a screening program. The cost analysis and cost effectiveness remain to be defined, along with the test performance characteristics, how the test performs outside of a clinical study, and patients' acceptance of the test. It appears that acceptability is higher than for standard FIT or the fecal occult blood test.

No screening is not an option. Any screening is better than nothing. We have a screening gap of approximately 20%; we are going to need to increase screening rates from 60% to 80% by 2018. Hopefully, this will stimulate discussions between patients and their healthcare providers. Colonoscopy is still the preferred strategy, but for anything that raises the awareness of screening and acceptability of screening, I am all in.

This is Dr. David Johnson. Thanks for listening.

 

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