Your body creates certain markers in response to cancer. Some cancer cells also have their own markers. These “biomarkers” can be in the blood, and two FDA approved colorectal cancer tests may be able to screen for them.

Colorectal cancer (CRC) is one of the most common types of cancer in the United States, making early detection and treatment very important.

CRC screening often involves a colonoscopy or stool-based tests. Another type of less invasive blood test can look for biomarkers of CRC. This test has potential, though it’s not standard yet in screening.

A blood-based biomarker test (also called a tumor marker blood test) looks for signs of cancer, known as biomarkers, in your blood.

Biomarkers are anything that cancer cells make or your body produces in response to cancer. They often include proteins or specific changes related to nucleic acids (DNA or RNA).

A clinician collects a blood sample from a vein in your arm and sends it to a lab for analysis.

Looking for biomarkers can help inform a doctor about:

  • whether cancer may be present
  • if specific treatment types may be more effective for a cancer
  • how well a current cancer treatment is working
  • estimates of cancer outlook

How are blood-based biomarkers used now?

Blood-based biomarker tests are generally used more for treatment and outlook purposes than for cancer screening and diagnosis. They’re used when cancer has already been diagnosed through other tests.

According to the American Cancer Society (ACS), two blood-based CRC screening tests are Food and Drug Administration (FDA) approved but haven’t been reviewed by the ACS or the United States Preventive Services Task Force (USPSTF).

While these tests can provide helpful information, blood biomarker tests aren’t typically used alone. Other tests are usually needed to lend support to their results.

What are the limitations of blood-based biomarker tests?

The use of blood-based biomarkers in CRC screening is still in its early stages. According to the National Cancer Institute, there are still some hurdles.

These are related to sensitivity and specificity. Ideally, a biomarker test for cancer screening should be both highly sensitive and highly specific.

A test with high sensitivity will detect cancer biomarkers in most people, but a test with low sensitivity may not. This means that more screening tests may be needed to see if cancer is present.

A test with high specificity will find cancer-specific biomarkers. However, when specificity is low, you may get more false positives. This can lead to overdiagnosis or additional testing.

Other limitations of blood-based biomarker tests include:

  • they can miss many precancerous growths (polyps) and some cancers
  • insurance may not cover some blood tests
  • a colonoscopy will still need to be performed if results are atypical

Two blood-based biomarker tests are currently available and FDA approved for CRC screening for people who are at average risk for colon cancer:

  • Shield: Approved in 2024, the Shield test looks for DNA floating freely in the blood (cell-free DNA) and any changes to this DNA that might indicate the presence of a tumor or polyps in the colon. This test is for those at least 45 years of age who need to undergo CRC screening.
  • ColoHealth (previously Epi proColon): Approved in 2016, the ColoHealth test looks for a specific change to DNA called methylation, which may change how a gene is expressed. This test specifically looks for methylation in a certain area of a gene called Septin 9 (SEPT9). The presence of methylation here is associated with CRC. This test is for those 50 years of age and older who have not completed CRC screening.

However, neither tests are meant to replace standard CRC screening tests, like a colonoscopy. If results come back positive or abnormal, it should be followed up with a colonoscopy.

How accurate is each test?

Shield

According to a 2024 study of nearly 8,000 people, Shield helped detect CRCs in more than 83% of the participants who were found to have CRC based on colonoscopy.

It’s estimated that 1 out of 10 people who do not have advanced abnormal cells will have a false positive test result.

ColoHealth

An early study of the ColoHealth test found that overall sensitivity was 48%. However, specificity was higher at about 92%.

Because ColoHealth has lower sensitivity, it may miss some CRCs that could have been found using other methods.

Another early study compared the ColoHealth test with a biomarker stool test for CRC. It found that the ColoHealth test had comparable sensitivity to the stool test, but its specificity was much lower.

A 2019 review noted that the ColoHealth test may increase CRC screening in people who decline screening by colonoscopy.

However, that review also raised concerns that some people may begin to opt for ColoHealth in lieu of other screening tests.

A 2022 study looked into ColoHealth as a less invasive way to screen for early-onset CRC. The researchers found that the test was quite sensitive and specific for this purpose.

Are the tests covered by insurance?

Whether the Shield or ColoHealth test is covered by your insurance depends on your provider. Because they have not been reviewed by the ACS or USPSTF, they might not be fully covered by private insurance.

It’s a good rule of thumb to check in with your insurance provider if you’re ever unsure about whether a particular test is covered.

Medicare Part B covers the Shield blood test for CRC screening without out-of-pocket costs.

The Centers for Medicare and Medicaid Services (CMS), which administers Medicare, states that the ColoHealth test doesn’t meet its sensitivity and specificity criteria for coverage.

A couple of additional blood-based biomarkers may be used for CRC screening. These are also discussed in relation to treatment and outlook rather than diagnosis:

  • Circulating tumor cells: Generally, circulating tumor cells are associated with a less favorable CRC outlook. Their presence may indicate that the cancer has spread beyond the large intestine to distant organs such as the liver, lungs, or brain.
  • Tumor DNA: Tumor DNA can also be analyzed for certain changes, like the ColoHealth test. Some of the changes, like those in the genes KRAS and BRAF, may indicate that a CRC may be resistant to certain treatments.
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Doctors and scientists are working hard to identify and characterize new biomarkers for CRC and improve strategies for detecting and measuring CRC biomarkers that have already been identified.

Two newer types of blood-based biomarkers for CRC are microRNA (miRNA) and long noncoding RNA (lncRNA).

  • miRNA: These may control what proteins cells make and may sometimes be found in the blood. Research has documented changes in the levels of certain miRNAs in CRC compared with healthy individuals.
  • lncRNA: These are also sometimes found in the blood and may regulate gene expression. A 2022 review notes that many lncRNAs have been associated with all stages of CRC.

Researchers are hoping to learn more about exactly how these molecules are associated with different aspects of CRC.

Blood-based biomarkers aren’t just used for CRC. They’re also being investigated for cancers of the lung, breast, and more. They’re even being looked at for early detection of Alzheimer’s disease.

Blood-based biomarker tests are sometimes used to assess cancer treatment and outlook. However, their use in cancer screening and diagnosis still remains limited at this time.

Two blood-based biomarker tests are currently FDA approved for CRC. However, because of concerns regarding their sensitivity and specificity, they are not recommended as part of standard CRC screening guidelines.

Talk with your doctor about your CRC risk and when you should start screening. They can also recommend which screening tests would be a good fit for you.