What Is a Liquid Biopsy?

What to expect when undergoing this test

In This Article

A liquid biopsy, also referred to as rapid plasma genotyping, is used to look for cancer cells circulating in the blood or to detect genetic mutations in these cells. Results of the test help determine whether a cancer might respond to treatment with targeted therapies or if the cells have undergone any changes since the initial diagnosis or treatment. While liquid biopsy can be used for several cancer types, there is certain interest in its use for lung cancer—our focus here.

Researchers are still studying all the ways that liquid biopsy testing can help to diagnose cancer or direct treatment. Already, it's a trusted alternative to traditional tissue biopsies in certain situations and is relied on as an important tool to help doctors manage care for patients.

Although the blood test has limitations, it is less invasive and safer than a tissue biopsy, which can result in some complications. Liquid biopsy also shows hope for detecting information about drug resistance or molecular changes in cancer cells that can better guide treatment recommendations. For lung cancer patients, this applies to both non-small cell lung cancer (the most common type) and small cell lung cancer (the most aggressive).

Purpose of a Liquid Biopsy

A liquid biopsy blood test is such a new tool that its full potential is still being explored. Currently, it offers some assistance with diagnosing cancer. However, it is primarily used to help with determining a course of treatment or monitoring the effectiveness of treatments that are being tried.

Role in Diagnosis

Image testing such as computed tomography (CT) scans and chest X-rays along with tissue biopsies are the standard tools employed for an initial diagnosis of lung cancer. However, liquid biopsies are increasingly being used as an auxiliary tool in the diagnostic process when, for instance, a CT scan shows an abnormality.

Cells and parts of cells frequently break off from a lung cancer tumor and enter the bloodstream. This happens even in the early stages of lung cancer before the cancer metastasizes, or spreads. By looking at a sample of your blood, it's possible to check for these fragments. If they're present, it will support a lung cancer diagnosis. The fragments will then be analyzed to gain information about your cancer.

Often, a liquid biopsy is ordered in addition to a tissue biopsy, but a doctor may choose to only order the simple blood test for several reasons:

  • Less invasive: Tissue biopsies require doctors to use a needle or a surgical incision to remove a sample of tissue from the lung.
  • Safer: Traditional biopsies carry the risk of complications including infections and pneumothorax (collapsed lung).
  • Tumor location: If tumors are in places that are difficult or dangerous to access, a tissue sample cannot be obtained.
  • Easy comparisons: Doctors can take multiple blood samples over time to follow changes in a cancer.
  • Effectiveness: Research shows that a liquid biopsy is as effective as a tissue biopsy in detecting the presence of all treatable genetic mutations in non-small cell lung cancer.

A liquid biopsy may be particularly advantageous when a tissue biopsy results in insufficient tissue collection. It is much easier to repeat a blood test than repeat a tissue biopsy.

Using liquid biopsies as part of the diagnostic process allows doctors to do more than just confirm if cancer is present—it allows them to determine what type of lung cancer they're dealing with. Specifically, doctors check for biomarkers in your blood. These biomarkers are substances released by the tumors that can indicate gene mutations.

More Comprehensive Analysis

Liquid biopsies offer another advantage. Lung cancers are heterogeneous, meaning that different parts of a tumor (and especially different tumors such as the primary tumor and a metastasis) may be somewhat different in their molecular characteristics.

For example, a mutation present in cancer cells in one part of the tumor may not be present in cells in another part of the tumor. To understand this, it's helpful to realize that cancers are continually changing, developing new characteristics and mutations.

A conventional biopsy is limited in that it samples only one specific area of tissue—one area where all the cells are alike. A liquid biopsy, in contrast, may be more likely to reflect the mixed characteristics of the tumor as a whole. This gives your doctor a more complete picture of what is needed to fight the cancer.

Types of Liquid Biopsies

In testing liquid biopsy blood samples, scientists currently search for several biomarkers.

Circulating Tumor Cells (CTCs)

CTCs refer to tumor cells that can be found in the bloodstream of some people with cancer. There is some evidence that CTCs may be extremely helpful when determining treatment and prognosis for small cell lung cancer since it's estimated that 85% of people with this diagnosis have CTCs, which are associated with poor prognosis.

A CTC count is usually done before and after treatment. If levels decrease after surgery or chemotherapy, it's likely that you're in remission; a higher count indicates the disease is progressing and new therapies should be considered.

Cell-Free (Circulating) Tumor DNA (ctDNA)

Analyzing fragments of tumor cells in your blood, doctors can detect ctDNA. This is used to diagnose EGFR mutations. This mutation allows lung cancer cells to quickly multiply and spread.

Once doctors identify that cells have this mutation, they can target the cells with specific medications that stop this rapid cell division. They will then continue to monitor your cells with this blood test to check for resistance to those medications.

Tumor RNA in Platelets

Tumor RNA in platelets is discussed less often than CTCs and ctDNA, but it's another important substance clinicians look for with liquid biopsies. Platelets are known for their ability to take up RNA from tumors and may play a role in the spread of cancer.

Risks and Contradictions

Liquid biopsies are now used routinely. But as with many rapidly adopted tests, there has been some controversy surrounding them. It's common for the accuracy of liquid biopsies to be questioned relative to tissue biopsies.

Lower Sensitivity

Studies have shown that the findings of genetic testing on liquid biopsy specimens closely match findings on tissue biopsy samples when the results are positive. However, these blood tests are not as sensitive as tissue samplings. This means that liquid biopsies do not always pick up early-stage cancers and, according to some studies, may only be appropriate for patients with advanced cancer.

Thus, researchers usually say that negative liquid biopsy results should not be used to guide therapy. In cases where a liquid biopsy yields a negative reading, additional testing is needed to confirm a diagnosis.

Because of low sensitivity, liquid biopsy testing can't be relied upon as the only—or even the primary—diagnostic tool for lung cancer.

Tissue biopsies allow pathologists to analyze complete cells within tumors, rather than fragments of DNA, so they remain the standard for diagnosing cancer. For greater accuracy, oncologists often send both tissue and liquid biopsy samples out for genomic sequencing.

Lab Bias

The newness of liquid biopsy testing means that the laboratories have not yet developed a high level of consistency when it comes to analyzing the samples. This leads to variations in how tests are read. A system that ensures appropriate, uniform processes and addresses the potential for over-interpretation is needed.

Before the Test

Your liquid biopsy will likely be ordered after you have undergone other screenings for lung cancer including, perhaps, a tissue biopsy. The blood draw may be done in a doctor's office or at a testing facility.

Typically, you don't need to fast before the blood test, and no preparation is required. Unless you're told not to drink before the test, be sure to be well hydrated; it will help the phlebotomist find your vein so the draw will go more smoothly.

Your doctor may alter your medications or ask you to delay taking some prior to the blood draw. Discuss this with your doctor beforehand.

During the Test

A liquid biopsy is conducted similar to a routine blood test:

  • The phlebotomist will clean the area where the puncture will be made (usually the elbow crease).
  • A tourniquet will be tied around your upper arm above the site where blood will be drawn.
  • You may be asked to pump your fist to get the vein primed.
  • A needle will be gently inserted into the vein and blood will be collected.
  • The phlebotomist will untie the tourniquet, withdraw the needle, and apply pressure on the puncture site to stop any bleeding.
  • A bandage will be placed over the small wound.

If you get nervous at the sight of needles or blood, you may want to practice deep breathing exercises, which can help you calm down and get through the process.

After the Test

The blood sample may be sent out the same day your blood is drawn, and results from a liquid biopsy may be returned within two weeks or less.

If results indicate that you're negative for a specific test, your doctor may order a tissue biopsy to confirm the findings if you haven't yet had that procedure.

For instance, a negative ctDNA reading would indicate that you do not have EGFR mutation. But since liquid biopsy tests tend to have high rates of false-negatives, more confirmation of this is needed.

Interpreting Results

CTC counts provide the number of CTCs in a specified volume of blood. The report will label these as either favorable or unfavorable:

  • Lower CTC counts (favorable) are associated with better survival rates.
  • If the CTC count doesn’t go down after treatments, your doctor will know that it’s time to try a new approach.

Your report may also note whether your ctDNA test is positive or negative. A positive result indicates that your tumor has an EGFR mutation. This type of mutation may respond to targeted therapy drugs such as Tarceva (erlotinib).

If you have already been on this medication, a liquid biopsy test can detect whether you have another mutation that would cause resistance to Tarceva. If that's the case, your doctor will switch you to a new treatment such as Tagrisso (osimertinib) or Iressa (gefitinib).

Other Considerations

There are two areas of lung cancer management in which ctDNA may play a greater role in the future:

  • Detecting resistance to targeted therapy medications before it's even clear from a CT scan that the cancer is progressing and the treatment isn't working
  • Diagnosing lung cancer early by detecting ctDNA from tumor cells before a tumor is seen on a CT screening

Right now, high costs for repeated tests and the lack of sensitivity on liquid biopsies prevent doctors from taking advantage of opportunities to do early screenings or track treatment resistancy, but researchers continue to look at ways to make it possible.

A Word From Verywell

The science related to liquid biopsies and genomic sequencing is changing rapidly, making it challenging for oncologists—especially those who treat a wide range of cancers—to stay abreast of the changes. If your doctor doesn't offer genetic testing, it may be worthwhile to look at getting a second opinion. You may want to seek out a different treatment center that will conduct a liquid biopsy and can verify whether you'd be a good candidate for newer approaches to treatment that can help you manage your lung cancer.

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Article Sources
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