Exact Sciences completed 1.69 million Cologuard tests in 2019, and while the test was found to have 92 percent sensitivity and 87 percent specificity rates for detecting colorectal cancer, it remains divisive in the medical community.
The majority of orders for Exact's multitarget stool DNA test come from primary care physicians, with gastroenterologists making up a much smaller percentage. However, Exact is developing a new iteration of the test that aims to have higher sensitivity and specificity rates. Over the last three years, Becker's has aimed to collect responses from gastroenterologists on whether they'd recommend Cologuard.
Here, we present viewpoints from two gastroenterologists on Cologuard, reconnect with a gastroenterologist from the first time we ran the piece, and explore Cologuard 2.0 with Exact Sciences Chief Medical Officer for Screening Paul Limburg, MD.
Note: Responses were edited for style and clarity.
Here, two gastroenterologists share their thoughts on Cologuard:
Harish Gagneja, MD, gastroenterologist at Austin (Texas) Gastroenterology: I don't recommend Cologuard as a first-line test because:
- Colonoscopy is a preventive test while Cologuard is a screening test.
- Cologuard has high false positive rates.
- Cologuard doesn't differentiate between whether it is a genetic test positive or fecal immunochemical test positive. FIT tests for hidden blood in the stools, while Cologuard is a combination of the two tests.
- If a Cologuard test returns positive, a colonoscopy [is needed which] becomes a diagnostic test and patients are responsible for their copays/coinsurance. [Colonoscopy] is no longer considered a screening test for the patients.
- Follow-up intervals for the Cologuard testing are based on arbitrary numbers and not based on a scientific study.
However, I would use Cologuard if a patient is not willing to undergo colonoscopy, as something is better than nothing.
Jesse Houghton, MD, senior medical director of gastroenterology at Southern Ohio Medical Center (Portsmouth): I truly believe that Cologuard will eventually, by and large, replace the purely screening colonoscopy at some point in the future. Now, it is not there yet, and I have been educating my patients and referring primary docs about its limitations, which I have included below. Cologuard is:
- Not indicated for patients who already have a personal history of adenomas or who have a family history of colon cancer — these patients should continue with colonoscopy
- Not tested for polyps less than 1 centimeter in size, which is the majority of polyps that we find during colonoscopy
- Much less sensitive for colon polyps compared to colon cancer, touting 69.2 percent sensitivity for adenomas with high-grade dysplasia and only 42.4 percent sensitivity rates for adenomas or tubulovillous adenomas greater than 1 centimeter
- Has lower sensitivity (75 percent) for stage 4 colon cancer than other stages
- Has a false positive rate of  percent
That said, once the scientific team at Exact Sciences can improve on the above shortcomings, it's bye bye screening colonoscopy, assuming a negative Cologuard. As a GI doc who spends about 90 percent of my time scoping, I am not looking forward to that day; however, I am realistic about it coming.
Here, Pradeep Kumar, MD, with Austin Gastroenterology, revisits his thoughts on Cologuard and examines what Cologuard 2.0 could bring about:
Pradeep Kumar, MD, gastroenterologist with Austin Gastroenterology: Cologuard is a valuable test for those who would otherwise refuse colonoscopy. It is better than doing nothing in order to detect precancerous polyps which may progress into colon cancer unless removed via colonoscopy and polypectomy.
I found then and I find now that Cologuard, while filling that niche, continues to market [itself] in a way that equates it to colonoscopy in detecting polyps by invoking that "no prep is necessary." It inaccurately depicts the nature of colon cancer prevention by marketing its cancer detection accuracy rate as 92 percent. That completely ignores that colon cancer prevention strategies have always been aimed at finding and removing precancerous polyps, not finding and detecting cancer.
I do understand that reporting an accuracy rate of 42 percent of detecting the highest risk polyps, as they do on their website, would not sell more products. Their hiring of a legion of sales force all saying the same things only adds to my frustration with them. It's like marketing tobacco to teenagers.
[On Cologuard 2.0], I appreciate measures to improve sensitivity and specificity, but [I] also view this as more of a marketing ploy, knowing their past tactics. The only important piece of data that they can report is its negative predictive value. If the test is negative, how likely is it that the patient does not indeed have a dangerous high-risk polyp? When a company with this past works on sensitivity and specificity, I expect they will tweak their true and false positive rates in order to make their numbers look good, while ignoring the measure that will truly save people's lives.
Here, Dr. Limburg explains the next generation of test, Cologuard 2.0:
Paul Limburg, MD, gastroenterologist at Mayo Clinic (Rochester, Minn.): CRC screening tests that are accurate, accessible and acceptable to both patients and providers offer the best opportunity to detect and remove precancerous polyps and find early-stage cancers that can be most effectively treated. Cologuard, the only FDA-approved, multitarget stool DNA test, detects 94 percent of early-stage cancer and 92 percent of all colorectal cancer at 87 percent specificity and can be used in the privacy of an individual's home. More than 3.5 million people have been screened for colorectal cancer using Cologuard since [it earned] FDA approval in 2014.
The Exact Sciences team is constantly innovating to advance our mission and help deliver earlier, smarter answers across the cancer journey. We're developing Cologuard 2.0 to further enhance an already high-performing CRC screening option. Our primary goal is to increase Cologuard's specificity while maintaining a high level of sensitivity. In collaboration with Mayo Clinic, we have identified novel markers and improved laboratory processes that show considerable promise for improving assay performance. In a study, presented at the American College of Gastroenterology's 2019 annual meeting, the novel marker panel demonstrated increased test specificity of 92 percent, while maintaining colorectal cancer sensitivity of 92 percent. Following these promising results, we initiated a 10,000-patient prospective study, BLUE-C, to validate the performance of the enhanced test and prepare for FDA submission. We're also working to improve the patient experience by enhancing the buffer solution to extend the stability of the sample, providing more flexibility in how quickly they must return Cologuard kits to our laboratory for analysis. These are exciting steps toward developing and delivering an even more accurate, patient-friendly option for average-risk colorectal cancer screening.
We look forward to generating additional evidence, making an enhanced test available to better serve individuals and healthcare providers, and solidifying Exact Sciences as the leader in the early detection of colorectal cancer.
Disclosures: Dr. Limburg serves as chief medical officer of the screening business unit for Exact Sciences through a contracted services agreement with Mayo Clinic. Dr. Limburg and Mayo Clinic have contractual rights to receive royalties through this agreement.