Colorectal cancer (CRC) starts in the colon or rectum, the areas that make up your large intestine. The large intestine absorbs water and salt from food, and stores the leftover waste until it can be expelled during a bowel movement.

According to the American Cancer Society (ACS), CRC is the third most common type of cancer in the United States. It’s also the third-leading cause of cancer death, making early detection and treatment very important.

Colorectal cancer screening often involves having a colonoscopy or stool-based tests. However, another type of less invasive blood test can look for biomarkers of colorectal cancer. This kind of test has potential, though it’s not standard yet in screening.

In this article we’ll take a closer look at blood-based biomarker tests, how they may be used for CRC, and what the current CRC screening guidelines say.

Simply put, a blood-based biomarker test looks for signs of cancer-specific markers in the body. It uses a sample of blood collected from a vein in your arm to do this.

Cancer-specific markers are basically anything that’s made by cancer cells or produced by your body in response to cancer. They often include proteins or specific changes related to nucleic acids (DNA or RNA).

Looking for these 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 may be working
  • estimates of cancer outlook

How are blood-based biomarkers used now?

For the most part, blood-based biomarker tests are currently used more for treatment and outlook purposes than for screening. An example of this is the CA-125 blood test, which is sometimes used for ovarian cancer.

CA-125 is made by ovarian cancer cells and can be present in the blood. A drop in CA-125 levels can indicate that a treatment is working. However, an increase can point to an ineffective treatment or a cancer recurrence after remission.

While these tests can give helpful information, it’s important to note that blood biomarker tests aren’t typically used by themselves. Other tests are usually needed to lend support to their results.

Using the example above, rising CA-125 levels may flag a potential recurrence of ovarian cancer. However, a doctor will still likely want to do imaging and other tests to get a better idea of what may be going on.

What about using blood-based biomarkers for screening?

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

These have to do with 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 pick up on everyone with these biomarkers. This means that more screening tests may be needed to see if cancer is present.

Meanwhile, a test with high specificity will find cancer biomarkers specific for only a certain type of cancer. However, when specificity is low, you may get more false positives. This can lead to overdiagnosis or additional testing.

There’s currently one blood-based biomarker test for colorectal cancer screening that’s been approved by the Food and Drug Administration (FDA). It’s called the Epi proColon test and was approved in 2016.

The Epi proColon test uses a blood sample to look for a specific change to DNA called methylation. Methylation is a type of change to your DNA that can regulate how a gene is expressed.

This test is specifically looking for methylation in a certain area of a gene called Septin 9 (SEPT9). The presence of methylation here is associated with CRC.

When is the Epi proColon test used?

The Epi proColon test is indicated for CRC screening in adults ages 50 and older who are at an average risk level. However, it isn’t meant to replace standard CRC screening tests, like a colonoscopy.

The manufacturer of the test states that typical CRC screening tests should be offered and declined prior to using the Epi proColon test. Further, they note that a diagnostic colonoscopy is still necessary after a positive Epi proColon result.

How accurate is the Epi proColon test?

An early study of the Epi proColon test was carried out in 2014. The test’s overall sensitivity was 48.2%. However, specificity was higher at 91.5%.

Another 2014 study compared the Epi proColon test with another biomarker test for CRC that uses a stool sample. It found that the Epi proColon test had comparable sensitivity to the stool test, but its specificity was much lower.

A 2019 review noted that the Epi proColon 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 Epi proColon in lieu of other screening tests. Because Epi proColon has lower sensitivity it may miss some CRCs that could have been found using other methods.

CRC is increasing in younger people. As such, a 2022 study looked into Epi proColon 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.

Is the Epi proColon test covered by insurance?

Whether the Epi proColon test is covered depends on the type of insurance you have. 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.

For example, Medicare states that they’ll cover an approved blood-based biomarker screening for CRC once every 3 years.

However, the Centers for Medicare and Medicaid Services (CMS), which administers Medicare, has said that the Epi proColon test doesn’t meet its sensitivity and specificity criteria for coverage.

How else are blood-based biomarkers used in colon cancer?

There are several additional biomarkers that may be used for colorectal cancer. Similar to what we’ve covered earlier, many of these are discussed in relation to treatment and outlook.

A 2019 review summarizes these biomarkers at length. Let’s have a brief look at a couple of these biomarkers.

  • Circulating tumor cells. Circulating tumor cells are cancer cells that are in the bloodstream. Generally speaking, circulating tumor cells are associated with poorer CRC outlook. Their presence may be an indicator that the cancer has spread beyond the large intestine to distant organs like the liver, lungs, or brain.
  • Tumor DNA. Tumor DNA in the blood can also be analyzed for certain changes, as in the Epi proColon test. Some of the changes, like those in the genes KRAS and BRAF, can indicate that a CRC may be resistant to certain treatments.

Doctors and scientists are working hard to identify and characterize new biomarkers for colorectal cancer. They’re also looking to improve strategies to detect and measure CRC biomarkers that have already been identified.

In addition to what we’ve already discussed, two newer types of blood-based biomarkers for CRC are microRNA (miRNA) and long noncoding RNA (lncRNA).

  • miRNA: These are small strands of RNA that can play a role in controlling the types of proteins cells make. They can sometimes be found in the bloodstream. Research has documented changes in the levels of certain miRNAs in CRC compared with healthy individuals.
  • lncRNA: These are longer strands of RNA that can also sometimes be found in the blood. lncRNAs can also play a role in regulating how genes are expressed. 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. In fact, they’re even being looked at for early detection of Alzheimer’s disease.

Generally speaking, the outlook for most cancers is greatly improved when it’s detected and treated early. CRC is no exception, meaning that receiving regular screenings is vital.

When should you have CRC screening? What tests can you get? Let’s examine some of the guidelines now.

Both the U.S. Preventive Services Task Force and the ACS recommend that adults ages 45 to 75 who are at average risk be screened for CRC. The currently recommended screening test options include:

Currently, the Epi proColon test is not included as a recommended test for CRC screening.

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

There’s currently one FDA-approved blood-based biomarker test for CRC. However, because there are concerns regarding its sensitivity and specificity, it’s currently not recommended as a part of standard CRC screening guidelines.

Colorectal cancer is the third-leading cause of cancer death in the United States. As such, talk with your doctor about your CRC risk level and when you should start screening. They can also recommend which screening tests would be a good fit for you.