The Benefits and Risks of Using Liquid Biopsy for CRC Screening

The FDA approved Guardant Health’s Shield blood test for colorectal cancer (CRC) screening in patients who are at an average risk of being diagnosed with the condition on July 29, 2024.¹ The approval came as a welcome alternative to colonoscopy, fecal immunochemical testing (FIT), and at-home Cologuard testing for the detection of CRC. However, with the approval comes the need to educate patients on what to expect from such a test and what the advantages and disadvantages of the test are.

Guardant Health Shield Test Approved by FDA

The FDA approval of the Guardant Health Shield blood test marked the first time that a blood test has been approved as a primary method of CRC screening that can be covered by Medicare.¹ With the screening rate for CRC at only 59% in the United States due to the current invasive or unpleasant methods of screening, a blood test may offer an alternative that is both easier to collect and easier to convince patients to take.

“The fact that circulating free DNA that's associated with colon cancers can be detected in blood is a significant scientific advance, and something that we have been hoping for for a long time,” said David Lieberman, MD, a colorectal cancer expert from the American Gastroenterological Association.

The blood test was found capable of detecting stages II, III, and IV tumors with high specificity, due to later stages of cancer releasing more DNA into the blood stream. The blood test can be as simple as requesting one from a doctor or a doctor including it to routine blood work. Early release of the blood test showed a 90% completion rate when a patient was prescribed the test, which could significantly improve screening rates in the country.

“I think the basic thing that we all need to recognize in terms of colon cancer screening, is that the test that gets done is the best test,” said Howard Hochster, MD, FACP, associate director for clinical research and director of GI oncology at Rutgers Cancer Institute. “There are a lot of people who do not want to have colonoscopy, no matter what you tell them about it, they just are not going to do that. So, for those people, I think this is a pretty good alternative.”

With the added bonus of the test being covered by Medicare,² the affordability and accessibility of the test is a significant advantage to recruiting patients on Medicare, who are the target demographic, to get their routine screening. For patients at an average risk of CRC, this could provide a suitable alternative for people who are averse to using a colonoscopy.

However, there are some disadvantages that should be acknowledged before a patient uses the blood test.

Blood Test: Challenges to Application

Although the blood test has a lot of advantages for patients who are avoiding their screening for CRC due to not wanting to use the FIT or Cologuard tests at home or not wanting to schedule a colonoscopy, there are some distinct weaknesses of the blood test that should be communicated to patients prior to the test being administered.

A major issue, Lieberman and Hochster said, was that the test did not have a high specificity for stage I cancer and for lesions, with only 13% of lesions detected in patients in the ECLIPSE study results published in the New England Journal of Medicine.³

David Lieberman, MD

“The other aspect of colon cancer screening is not just cancer detection, but it's also cancer prevention. And the way that cancers can be prevented with screening is to detect important cancer precursor lesions. If those are detected, and they can be removed, cancers can be prevented,” said Lieberman. The lack of sensitivity for these lesions could spell a significant problem if the blood test is used on its own. Lieberman also believes that only using the blood test will put patients at a higher risk of having CRC and mortality due to CRC compared with using colonoscopy or FIT tests due to the lack of precursor lesion detection.

Hochster noted that the blood test also turned up a significant number of false positives when used in patients. According to the study published in the New England Journal of Medicine,³ a total of 10.4% of patients who did not have an advanced colorectal neoplasia after having a colonoscopy test were incorrectly indicated as having a positive cfDNA blood-based test, which led to a specificity for negative colonoscopy of 89.9%.

“If you tested 100,000 patients, they said…about 9000, some of those will be positive, even though they don't have colon cancer and 80,000 will be negative,” said Hochster. “So there are more than 9000 who are going to have a positive test that don't have cancer.” These results could make patients nervous should they be told that their test came back with abnormalities. Hochster noted it was incredibly important to let patients know that this is a possibility before they receive the test in order to properly prepare the patient for any positive result.

Lieberman also discussed the potential cost of such a test. Lieberman said that, when using models to predict cost of a test at a workshop panel,⁴ they found that, should the blood test be priced similarly to the Cologuard test, it would be very costly compared with a colonoscopy if patients have to cover the cost. The test could be more cost-effective if the cost of the blood test is established as less than that of Cologuard, but that is currently unknown.

“If this is considered an approved colon cancer screening test, if it is approved and recommended by the US Preventive Services Task Force, then it theoretically would fall under coverage in the Affordable Care Act for a preventive care measure and should be covered without cost to the patient,” he said. Although Medicare is set to cover Shield, commercial insurance coverage is still pending.⁵

Lieberman last noted that there could be equity issues in regard to insurance coverage and whether patients would be able to access a medical facility to get their blood drawn, given things like FIT tests and Cologuard can be mailed, and blood tests can’t. If the patient has to get a colonoscopy to follow-up, that could also present a challenge for patients in rural areas who have to drive hundreds of miles to get to a facility.

Future Use of Shield Blood Test in CRC Screening

Although there are some challenges related to incorporating blood tests into cancer screening in the future, there are a lot of benefits to having an accessible screening option for patients.

Howard Hochster, MD, FACP

Hochster emphasized that a completed test is better than a test that isn’t done at all. Having a blood test may convince more people to get screening done and could reduce the number of colonoscopies performed each year. “A lot of people don’t get screened for colonoscopy…So if we use this test to get rid of a lot of people who don't need colonoscopy, then I think colonoscopy could have a much higher yield and be used more appropriately by people who actually need it,” Hochster said.

He also noted that increasing the screening rate for CRC is a paramount benefit to the blood test, as it has good specificity and is more appealing than the current options. “The benefits of the blood test are that it’s acceptable to a lot of people who wouldn’t do the other tests, [and] if you have a negative test, you’re pretty likely not to have colon cancer,” he said. “I think that’s a good deal for most people, because 9 out of 10 times you’re [going to] walk away reassured you don’t have colon cancer.”

Making sure that patients understand the limits to the approved blood test and the possibilities for both false negatives and false positives is important, Lieberman and Hochster agreed. This includes following up with the patient to make sure that any abnormal results are properly addressed and receive a colonoscopy to confirm the results.

“I think this a game changer in many ways because of the ease of performing a blood test compared with the other tests. And I guess that my only concern is that I think it's going to be important for patients to understand that while this test can be effective, it may not be as effective as the currently recommended tests. So they need to go into [the test] understanding that,” said Lieberman.

However, making sure that younger patients are aware that CRC is becoming more common in younger populations could help in increasing the screening rate. Hochster said that although detection of polyps should be a primary concern for blood tests developed in the future, the current one can detect enough that it is still worth taking.

“Colon cancer is largely preventable. The more people who are screened, the more we can reduce the incidence of colon cancer. This test will definitely help us pick up some of the colon cancers at an earlier stage,” Hochster said.

The Guardant Health Shield blood test for screening in CRC is a major addition to the screening lineup. Its non-invasive nature will present an appealing alternative to colonoscopies, FIT, and Cologuard testing. Although primary care providers should discuss the benefits and risks of the new blood test before using it as a primary screening method, overall, the test is a promising method for catching CRC in patients.

References

1. Bonavitacola J. Blood test approved by FDA for screening for colorectal cancer. July 29, 2024. Accessed August 7, 2024. https://www.ajmc.com/view/blood-test-approved-by-fda-for-screening-for-colorectal-cancer
2. Guardant Health’s FDA-approved Shield Blood Test now commercially available in U.S. as a primary screening option for colorectal cancer. News release. Guardant Health. August 1, 2024. Accessed August 14, 2024. https://investors.guardanthealth.com/press-releases/press-releases/2024/Guardant-Healths-FDA-approved-Shield-Blood-Test-Now-Commercially-Available-in-U.S.-as-a-Primary-Screening-Option-for-Colorectal-Cancer/default.aspx
3. Chung DC, Gray DM II, Singh H, et al. A cell-free DNA blood-based test for colorectal cancer screening. N Engl J Med. 2024;390:973-983. doi:10.1056/NEJMoa2304714
4. New data offer reality check on blood-based colorectal cancer screening. News release. American Gastroentrological Association. March 26, 2024. Accessed August 7, 2024. https://gastro.org/press-releases/new-data-offer-reality-check-on-blood-based-colorectal-cancer-screening/
5. Guardant Health’s FDA-approved Shield blood test now commercially available in U.S. as a primary screening option for colorectal cancer. News release. Guardant. August 1, 2024. Accessed August 7, 2024. https://investors.guardanthealth.com/press-releases/press-releases/2024/Guardant-Healths-FDA-approved-Shield-Blood-Test-Now-Commercially-Available-in-U.S.-as-a-Primary-Screening-Option-for-Colorectal-Cancer/default.aspx