What Is a Liquid Biopsy? How ctDNA Testing Works

By: David Grew MD MPH

"A liquid biopsy can sometimes help doctors learn about a tumor from a simple blood sample."

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A liquid biopsy is a test that looks for cancer-related material in a body fluid, most often blood. In cancer care, one common target is circulating tumor DNA, or ctDNA. ctDNA is small pieces of DNA that come from tumor cells and can sometimes be found in the bloodstream. Liquid biopsies may also look for other tumor-related material, not just ctDNA.

For patients, the appeal is easy to understand. A liquid biopsy is usually less invasive than a traditional tissue biopsy and can often be repeated more easily over time. But it is not a perfect replacement for a tissue biopsy in every situation.

What is ctDNA?

ctDNA stands for circulating tumor DNA. When cancer cells die or break apart, they can release fragments of their DNA into the blood. A blood test may be able to detect those fragments and look for cancer-related changes. 

This matters because DNA changes in a tumor can sometimes help doctors:

• identify treatment targets
• monitor how a treatment is working
• look for signs that cancer may be coming back
• understand why a treatment may have stopped working

How is a liquid biopsy different from a tissue biopsy?

A tissue biopsy removes a sample of the tumor itself. A liquid biopsy usually uses a blood sample. Because of that, liquid biopsies can be easier on patients and simpler to repeat.

But the two tests do not do exactly the same job.

A tissue biopsy can show doctors the actual tumor cells and how they are arranged in the tissue. A liquid biopsy does not provide that same kind of direct tissue information. Instead, it looks for tumor-related material that has been released into the blood or another fluid.

In some cases, a liquid biopsy can provide useful information when a tissue biopsy is hard to do or when doctors want to monitor changes over time. In other cases, a tissue biopsy is still needed.

How does ctDNA testing work?

The process usually starts with a blood draw. A laboratory then analyzes the sample to look for ctDNA and specific genetic changes linked to a person’s cancer. Different tests may look for different kinds of tumor-related signals, and not every liquid biopsy test works the same way.

One challenge is that there may be only a small amount of ctDNA in the blood, especially in some settings. That means a liquid biopsy may not always detect cancer-related material even when cancer is present.

When might doctors use a liquid biopsy?

Depending on the cancer type and the clinical situation, doctors may use liquid biopsy testing to help with:

• finding certain genetic changes that may guide treatment
• monitoring how cancer responds to therapy
• looking for evidence of residual or returning disease
• following cancer over time when repeated tissue biopsies would be difficult 

This is an area of active research, and the role of ctDNA testing is still expanding. Some uses are well established in certain cancers, while others are still being studied.

What are the advantages of a liquid biopsy?

A liquid biopsy may offer several benefits:

• it is usually less invasive
• it may be easier to repeat
• it may help capture tumor changes over time
• it can sometimes provide information when tissue is limited or hard to obtain

For patients, that can mean fewer procedures and, in some situations, faster access to useful information.

What are the limits of a liquid biopsy?

A liquid biopsy has important limits too.

Not all tumors shed enough ctDNA into the bloodstream to be detected. Some results may therefore miss a cancer-related change that is actually present. In addition, a liquid biopsy does not replace all the information doctors get from imaging, pathology, or tissue biopsy.

That is why doctors interpret liquid biopsy results in the larger context of the patient’s diagnosis, scans, symptoms, and other test results.

Why this matters for patients

Liquid biopsy and ctDNA testing are part of a broader shift toward more personalized cancer care. These tests may help doctors learn more about a tumor from a simple blood sample and, in some cases, make treatment decisions with less need for an invasive procedure. 

At the same time, it is important for patients to know that a liquid biopsy is not a magic test and is not right for every situation. The best way to understand whether ctDNA testing may be useful is to talk with your oncology team about your specific cancer and your specific treatment plan.

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To learn more about ctDNA, learn more from this video we made.

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FAQs:

Is a liquid biopsy always a blood test?
No. Blood is the most common sample, but the National Cancer Institute notes that liquid biopsy tests can also use other body fluids, such as urine, cerebrospinal fluid, or saliva. Which sample is used depends on the test and the clinical situation. If your doctor mentions liquid biopsy, ask what kind of sample will be collected and why.

Can a liquid biopsy replace a tissue biopsy?
No, not always. Liquid biopsy can be very helpful in some situations, but it does not fully replace the information doctors can get from a tissue biopsy. Some patients still need tissue testing to confirm the diagnosis or get a fuller picture of the cancer. Talk with your care team about why one test, or both, may be needed in your case.

Can a liquid biopsy miss cancer-related changes?
Yes. One reason is that there may be only a small amount of ctDNA in the blood, which can make detection harder. A negative result does not always mean there is no cancer-related DNA present. Your care team can explain what your result does and does not show.

Is ctDNA the same thing as cfDNA?
No. FDA explains that cell-free DNA (cfDNA) is DNA released into the bloodstream from dying cells in general, while ctDNA is the portion that comes specifically from tumor cells. That distinction matters because not all DNA found in blood is tumor DNA. If you see both terms on a report, ask your care team how the lab is using them.

Is liquid biopsy already used in cancer care, or is it still experimental?
Yes, it is already used in some parts of cancer care, but many uses are still being studied. Public sources from FDA, NCI, and NCCN describe liquid biopsy and ctDNA testing as important and growing tools in oncology, while also making clear that some applications remain emerging. Ask your doctor whether the use being considered in your case is standard practice, guideline-supported, or still investigational.

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