The Unique Use of Liquid Biopsy
Less invasive, but less common
Medically reviewed by Gagandeep Brar, MD
A liquid biopsy is a test to detect or monitor cancer that uses bodily fluids. There are many different types of liquid biopsy. Several are Food and Drug Administration (FDA)-approved, while others are in clinical trials.
Current liquid biopsy tests are used on non-small cell lung cancer, advanced breast cancer, colorectal cancer, and prostate cancer.
If you’re scheduled for a liquid biopsy, here’s what you need to know about the pros and cons of this biopsy type. This article will cover what cancer liquid biopsies can detect, the success rate of liquid biopsy diagnosis, and how it differs from other biopsies.
Photo Composite by Lecia Landis for Verywell Health
Purpose of Liquid Biopsy in Cancer Detection
The term liquid biopsy encompasses a wide variety of tests. Generally, these tests use bodily fluids that are relatively easy to access. These may include:
Blood
Urine
Saliva
The tests use these fluids to look for signs of cancer or to monitor if your cancer is growing or shrinking. These signs may include:
Cancer cells
Cancer genes, sometimes circulating tumor DNA (ctDNA)
RNA and proteins produced by cancer (biomarkers), including cancer antigen 125 (CA-125), associated with ovarian cancer, or prostate-specific antigen (PSA) associated with prostate cancer
Tiny bubbles of material produced by cells (exosomes)
Most FDA-approved liquid biopsies currently detect circulating tumor DNA. These are small pieces of DNA from dead or broken-down tumor cells. During cancer treatment, levels of this DNA drop as the tumors get smaller.
Even in people with advanced cancers, ctDNA makes up just a tiny amount of the DNA in the blood—about 1% to 2%—so it's hard to detect accurately. DNA fragments can also come from a fetus or placenta in a pregnant person or DNA from cardiac cells released during a heart attack or stroke.
Theoretically, liquid biopsies could be used in several different ways. They could:
Screen for early cancers
Augment tissue biopsies to get a more complete picture of cancer’s genetics
Track cancer’s growth or shrinkage during treatment
Monitor for cancer coming back
Used for cancers that can’t be removed with surgery and would be difficult to biopsy
Used for other applications for which tissue biopsies aren’t a good option
Help choose the best treatment option with genetic information from ctDNA
Indicate that cancer is becoming resistant and treatment should be switched based on genetic changes in ctDNA
Today’s liquid biopsy tests are not standard tests to screen or diagnose cancers. They are not sensitive or specific enough to be used alone and can give false positives (indicating cancer when there is none) and false negatives (not detecting cancer that is there).
Currently, liquid biopsies as a screening tool can’t tell us where cancer is, leading healthcare providers to pursue the source, sometimes without finding it.
Currently Available Liquid Biopsies for Cancer
Today’s liquid biopsies are used in the treatment of:
Some currently used liquid biopsies include:
CellSearch Circulating Tumor Cell test analyzes a blood sample for the presence of circulating tumor cells to see how well treatment is working for metastatic breast, colorectal, and prostate cancer.
The cobas EGFR Mutation Test v2 detects genetic changes in tumor cells from non-small cell lung cancer. These genetic changes can tell healthcare providers whether targeted therapy against epidermal growth factor receptor (EGFR) would be effective.
Guardant 360 companion diagnostic CDx tests 73 gene mutations in the ctDNA for non-small cell lung cancer.
FoundationOne Liquid CDx tests more than 300 genes in blood for non-small cell lung, prostate, ovarian, and breast cancer.
Dxcover Brain Cancer liquid biopsy analyzes blood serum concentrations of various biomarkers to detect brain cancers.
Oncimmune’s EarlyCDT-Lung liquid biopsy test looks for antibodies (immune proteins) against tumor-related proteins to find lung cancer early.
ExoDx Prostate IntelliScore is an exosome-based liquid biopsy that uses a urine sample to find people at risk of high-grade prostate cancer.
SelectMDx urine liquid biopsy looks for two biomarkers for prostate cancer.
Guardant Health’s Shield blood test looks for colorectal cancer using genetic and epigenetic changes in ctDNA and protein biomarkers.
Novigenix’s Colox test detects colorectal cancer from a blood sample by analyzing the peripheral blood mononuclear cells.
Biodesix‘s Nodify cdt finds lung cancer antibodies in the blood. Nodify xl2 looks for lung cancer proteins in blood.
Abcodia’s ROCA test uses a blood test for CA-125 to monitor ovarian cancer over time.
OPKO’s 4Kscore prostate cancer test is a follow-up blood test to determine the probability of finding aggressive prostate cancer after a high PSA test.
Pros and Cons of Liquid Biopsy
The most significant benefit of a liquid biopsy is that it requires only a blood draw or other fluid collection. There is no invasive procedure or surgery, which are sometimes required to collect a tissue biopsy. A liquid biopsy is less invasive and more easily repeatable than a tissue biopsy.
A tissue biopsy could miss the tumor or only sample some of the cells in a cancer that has multiple cell types. Liquid biopsies can be carried out rapidly and provide many different pieces of information, including details about the cancer’s genes, proteins, and metabolism.
Risks of Liquid Biopsy
The procedure for collection of a liquid biopsy is generally as low-risk as a blood draw. But in some cases, the results may lead to unnecessary testing, delays in diagnosis and treatment, false positives, or false negatives.
It’s possible that a liquid biopsy test for cancer can find ctDNA in a person’s blood months before cancer can be found by traditional methods. But these tests can also be false positives, causing fear and leading to unnecessary medical testing.
In some cases, these early cancers are not dangerous—they do not grow much or grow so slowly that they aren’t likely to cause harm.
For liquid biopsies meant to monitor a tumor’s genes for treatment decisions, the ctDNA may not adequately represent the DNA in the actual tumor. This could lead the healthcare provider to make the wrong treatment decision.
Another issue with ctDNA testing to screen for early cancers is that these tests can’t necessarily pinpoint where the tumor is in the body. Any positive must be checked using other imaging, potentially sending healthcare providers on a fruitless chase.
Costs of Liquid Biopsy
Liquid biopsies are generally cheaper than a tissue biopsy, but can still cost hundreds or even thousands of dollars. In some but not all cases, these tests are covered by insurance. Check with your insurance provider before getting a liquid biopsy to see whether your plan will cover your test.
Day of Liquid Biopsy
A liquid biopsy is generally painless and easy without requiring preparation. Each liquid biopsy test will be different, so speak with your healthcare provider about requirements specific to the test you’re taking.
Typically, a liquid biopsy will require a blood draw or urine collection. Sometimes, cerebrospinal fluid will be obtained with a lumbar puncture (spinal tap). Talk to your healthcare provider about the process for a lumbar puncture.
Before
Most of the time, you don’t need to do anything special before a blood draw or urine collection to prepare for it. Ask your healthcare provider if you should stop taking any medicines.
If you are collecting urine, ensure you have drunk enough fluids and not urinated in advance to produce enough urine for a good collection.
During
Liquid biopsies are fluid collections. A blood draw or urine collection is non-invasive. A liquid biopsy of blood will be no more painful than a traditional blood draw.
To draw blood, the healthcare professional will wrap a rubber band around your arm to make the vein more prominent. They will sterilize the draw site. They'll then use a needle to draw blood from a vein, typically from the arm, into a labeled tube. This is similar to any other blood test you may have. The blood is then sent to a laboratory.
If you have a peripherally inserted central catheter (PICC) line or other port, the healthcare professional may be able to draw the sample from there, minimizing pain and punctures.
If urine is collected, you'll be given a labeled sample container and directed to a restroom. Follow the instructions to get a good collection, which can vary depending on whether you have a vagina or a penis.
After
Depending on the test, getting test results from your liquid biopsy may take days or weeks. Your healthcare provider will review the test results with you and let you know what they mean for you and your next steps.
Understanding Liquid Biopsy Results
If your liquid biopsy is testing for tumor cells or tumor DNA, it may say these levels have increased or dropped. Lower levels would suggest treatment is working and the tumor is shrinking. If the results say the levels are higher, you may need more testing, like magnetic resonance imaging (MRI), to see if your cancer has grown or spread.
Other liquid biopsy test results may suggest that you’re a candidate for a specific targeted treatment.
Liquid Biopsy Compared to Other Types of Biopsy
A liquid biopsy varies considerably from other types of biopsy. They're used in different situations for various reasons. It is very unlikely that your healthcare provider will order a liquid biopsy as a diagnostic tool. You'll likely need a tissue biopsy of the tumor to diagnose cancer.
Tissue biopsies include core needle biopsies and fine needle aspiration biopsies. These are used to diagnose and treat most types of cancer.
Tissue biopsies take a small sample from a tumor or suspicious area. That tissue sample is analyzed in the lab to look for signs of cancer and do other testing to determine the type and stage of cancer.
When looking for gene changes in cancer with a ctDNA-based Guardant360 liquid biopsy, the liquid biopsy test results were similar to tissue biopsy for most people.
That being said, a review from the American Society of Clinical Oncology and the College of American Pathologists found most liquid biopsy test results don't completely match tissue biopsies. The differences could be due to the sample type or limitations of the tests.
Summary
A liquid biopsy is a non-invasive test that uses bodily fluids like blood, urine, and saliva. It may be used to detect and monitor cancer.
Liquid biopsies can detect circulating tumor DNA (ctDNA), RNA, proteins, and other biomarkers. Liquid biopsies are currently used for non-small cell lung cancer, breast cancer, ovarian cancer, prostate cancer, and colorectal cancer.
These tests have several potential applications, including screening for cancer, tracking how treatment is going, checking if cancer has come back, and helping make treatment choices.
However, there are limitations to liquid biopsies. They are not yet sensitive or specific enough to be cancer screening tools. False positives and negatives can occur. They can't pinpoint the location of cancer in the body. The ctDNA used in liquid biopsies may not always represent the DNA in the actual tumor.
On the positive side, liquid biopsies are less invasive. They're easily repeatable compared to tissue biopsies. They provide various information about cancer genetics, proteins, and metabolism. However, they may result in unnecessary testing, false results, or delays in diagnosis.
Liquid biopsies are generally cheaper than tissue biopsies but can still be costly. The availability of insurance coverage for these tests may vary. The procedure for a liquid biopsy is generally straightforward. They typically involve a blood draw or urine collection. The results may take days or weeks to process.
Liquid biopsies are typically used only in specific situations. Tissue biopsies are the primary method for diagnosing most cancers.
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