What are liquid biopsies?

A solid tumor is made of cells that are constantly turning over. This means that while some cells are dying, others are growing and dividing to replace these dead cells. A tumor grows if there is more cell division then cell death. A tumor shrinks if more cells in it die than divide. Therefore a tumor is stable when cell death rates are the same as cell division rates.

When cells die, they shed fragments of their DNA into the bloodstream. This is called circulating cell-free DNA, or cfDNA.

The same thing happens with tumor cells — and we call this circulating tumor DNA or ctDNA. We can think of this as “tumor trash” in the bloodstream.

ctDNA makes up only a tiny portion of the cfDNA found in your blood — but we can detect it. That’s because tumor DNA is different from healthy cell DNA due to the presence of specific mutations.

A blood test to detect ctDNA is often called a liquid biopsy, or a blood biopsy. Some tests require just a blood sample, others require a tumor sample as well.

If just a blood sample is used, we call this a tumor-naive test — meaning that the test checks for the same things for every patient with a standard panel. In a tumor-informed test, the company first evaluates your tumor, then creates an individual tumor-specific panel for screening your blood.

Tumor-naive ctDNA tests give results faster, while tumor-informed tests may have slightly better sensitivity.

How can liquid biopsies be used?

In general, there are two ways to use ctDNA tests:

1. Minimal residual disease (MRD) testing

MRD testing is frequently used for monitoring and surveillance. That means if they come back positive, you most likely have a tumor growing somewhere in your body.

The good news is these tests can often detect tumors before they are visible on scans, and prompt more frequent imaging tests to figure out where the tumor is.

These tests are most often used in early stage CRC, after patients have undergone treatment for their cancer. They may also be used in limited (often called oligometastatic) stage IV cancer, after patients have finished treatment.

Examples of this kind of testing include Signatera and Guardant REVEAL.

2. Mutation detection

The other kind of ctDNA test is aimed at detecting specific mutations in patients with growing tumors. These tests can also provide information on your tumor mutational burden (TMB) numbers.

Examples of this kind of test include Guardant 360 and Foundation One Liquid.

Pros of liquid biopsies:

These kind of tests can give you a glimpse at your disease in real time, because blood samples can be taken regularly. Blood samples are also less invasive than tumor tests, which require a tissue sample.

Cons of liquid biopsies:

Chemotherapy may suppress the release of ctDNA and affect your results. Also, these types of tests are relatively new — so doctors are still learning about accuracy, limitations, and the best ways to use them for surveillance.

Want to learn more about ctDNA tests for colorectal cancer? Check out this video:

What kind of liquid biopsies are there?

Let’s take a look at some of the common liquid biopsy tests that are being used at the moment.

Guardant360 CDx

The Guardant360 CDx test covers every guideline-recommended biomarker for those with advanced colorectal cancer, including MSI, expanded KRAS/NRAS, and BRAF mutations.

It’s important to note that Guardant360 CDx is different from Guardant360 — which provides extensive panel testing beyond the guideline-recommended biomarkers.

This video is a good introduction to the Guardant360 CDx test:

For more information on the test, as well as a copy of a sample report, check out this section of our Diagnosic and Surveillance Tests learning center.

Guardant REVEAL

Guardant REVEAL is the first ctDNA test for minimal residual disease (MRD) and recurrence monitoring that does not require tumor tissue. It only requires a blood sample.

The Guardant REVEAL test can be ordered approximately one month after surgery to determine if there is any cancer left in the body — or as regular surveillance at the end of treatment to help your doctor spot cancer recurrence early.

The results from Guardant REVEAL are available approximately one week after the sample is received.

What’s the difference between Guardant360 and Guardant REVEAL?

The Guardant REVEAL test is for patients with early-stage colon or rectal cancer (stage II-III). It looks for evidence of residual or remaining cancer after surgery or systemic treatment.

Guardant360 is a liquid biopsy test for patients with advanced colon or rectal cancer (stage IV). It provides comprehensive genotyping of an extended panel beyond the guideline-recommended biomarkers.

Learn more about the REVEAL test with Guardant’s Medical Science Liason Leslie Bucheit and PALTOWN’s Scientific Director Dr. Manju George:

For even more information, as well as a copy of a sample report, check out this section of our Diagnostic and Surveillance Tests learning center.

Signatera

Signatera is a new blood test that can identify molecular residual disease (MRD) or cancer recurrance by detecting ctDNA. This test also requires a tumor sample.

Signatera is a custom-designed test that is generated based on each patient’s unique set of tumor mutations. Knowing earlier if your cancer is likely to recur — or has progressed after treatment — can help you and your doctor have a more informed discussion on how to treat your disease.

Here’s a short introduction to Signatera, from Natera Oncology:

When should you consider Signatera?

At initial cancer diagnosis, to establish a baseline before surgery or treatment
After surgery, before starting chemotherapy
During treatment, to evaluate how well you’re responding to therapy
After treatment, to monitor for tumor response or molecular residual disease (the presence of ctDNA in your blood)

What’s the difference between Signatera and other ctDNA tests?

As we mentioned earlier, a Signatera test requires both tumor tissue and a blood sample to create a customized test.

Signatera can be ordered multiple times over the course of treatment or during follow-up visits to look for signs of recurrence. Once created, your doctor can asses whether there is any cancer left in the body with just a simple blood draw.