Liquid Biopsy: An Ultimate Guide

Updated July 9, 2019

This article was scientifically reviewed by YourDNA

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What is a liquid biopsy?

A biopsy is a process by which a piece of a person’s body is removed for analysis in a laboratory to detect cancer. A traditional biopsy involves the removal of a piece of tissue to be tested by a pathologist. Once removed, the tissue is examined under a microscope.

The pathologist notes the structure, shape and activity happening inside the cells to make a determination as to whether or not the cells are cancerous and, if so, what type of cancerous cells they are. Biopsy results inform prognosis and treatment.

What's in this Guide?

Disclaimer: Before You Read

It is important to know that your genes are not your destiny. There are various environmental and genetic factors working together to shape you. No matter your genetic makeup, maintain ideal blood pressure and glucose levels, avoid harmful alcohol intake, exercise regularly, get regular sleep. And for goodness sake, don't smoke.

Genetics is a quickly changing topic.

The traditional biopsy has some big shortcomings. Depending on where the cancer is suspected to be, a traditional biopsy can be painful, risky and invasive. In certain cases, it’s so difficult or dangerous to harvest a tissue sample that a traditional biopsy isn’t event possible.

A liquid biopsy, also referred to as a fluid biopsy, is a non-invasive alternative to the traditional tissue biopsy. Liquid biopsies can provide information about a person’s cancer to researchers and doctors.

More and more, biopsies are performed to detect genetic irregularities linked to cancer. For example, circulating tumor DNA (ctDNA) has become more regarded as a biomarker for cancer, increasing the popularity of what’s called a ctDNA liquid biopsy, which measures its presence in the blood.

Types of Liquid Biopsies

There are generally two types of liquid biopsies. The first looks at circulating tumor cells, while the other examines non-cellular matter found in the blood, such as DNA.

In recent years, there have been great strides in the usefulness and accuracy of the second type of liquid biopsy. In this case, free-floating DNA in the bloodstream is examined.

Tumors leave this kind of DNA behind as cells within the tumor die off. By sampling and studying this type of DNA, researchers and physicians have a chance to get a glimpse of the genetic mutations and additional regularities that are causing a tumor to grow.

Using this information, doctors may be able to decide which therapies are more likely to work with a patient’s specific type of cancer and which ones will not likely be as effective.

How Liquid Biopsies Work

A liquid biopsy works by looking for circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) in blood samples. Both ctDNA and CTCs are found in the blood but ctDNA is much (100x) more common. This makes ctDNA much easier to test.

The liquid biopsy procedure begins with a simple blood draw. The sample is added to a centrifuge and spun down to plasma. From there, Next Generation Sequencing (NGS) is used to find genetic mutations present in the sample that are associated with cancer. Results of the liquid biopsy may be ready in as little as two weeks.

What can we learn from liquid biopsies?

Beyond ctDNA analysis, you are likely wondering, “What are liquid biopsies useful for?” Perhaps most promising, is the liquid biopsies potential for early detection in individuals who have not even experience symptoms yet.

Another use of liquid biopsies is in the monitoring of treatment. Since they are non-invasive, unlike traditional biopsies, they are easily repeatable throughout treatment.

In one study, liquid biopsies were shown to be a successful method for monitoring metastatic melanoma.

In one study published in Cancer Discovery, liquid biopsies were touted as a tool for predicting a cancer relapse. In the application, liquid biopsies were used to identify new mutations in certain genes that were markers for an advanced melanoma relapse.

Liquid Biopsies in the Fight Against Cancer

Cancer remains one of the leading causes of death around the world, with the number of individuals experiencing cancer in their lifetime on the rise. Liquid biopsies present a promising evolution in the fight against cancer.

Of course, avoiding cancer is the ideal state, but early detection is the next best thing. Liquid biopsies present the potential to recognize all kinds of cancer—from Leukemia to prostate cancer to breast cancer and beyond—at an early enough stage for treatment to be more effective.

Liquid Biopsies and Precision Medicine Treatment

Precision medicine helps determine treatment based on specific genetic characteristics of a person’s disease. Liquid biopsies are one form of precision medicine.

Since the alternative tissue biopsy method is invasive and sometimes impossible to do, liquid biopsies are especially promising. According to J.P. Morgan, the liquid biopsy market is expected to reach $22 billion by 2020. The precision medicine market is set to reach $88 billion by 2023.

Accuracy of Liquid Biopsies

One issue with liquid biopsies is making sure the level of accuracy is adequate. In blood samples, minimal tumor DNA may be present, which makes it difficult to analyze and confidently detect mutations related to cancer.

For this reason, traditional tissue biopsies remain the number one tool for understanding the genetic characteristics of tumors in individuals with cancer.

In recent years, as liquid biopsies have become more accurate and the process more refined, the process has begun to approach the reliability and accuracy of traditional tissue biopsies in certain cases. Oxnard and Paweletz released a new study saying that rapid plasma genotyping, a specific approach to liquid biopsy, can quickly and accurately identify two key genes in tumors associated with the most common form of lung cancer, non-small cell lung cancer.

The results of the study were so well tested that Dana-Farber/Brigham and Women’s Cancer Center began offering this kind of liquid biopsy to all their patients with this type of lung cancer. They are the first medical facility in the country to do so and offer the testing to patients upon first diagnosis or in those who experience a relapse.

Accuracy is so important with liquid biopsies as false positives can cause very expensive and invasive treatments. One issue is that the level of ctDNA increases with age for everyone, even individuals without cancer, so there must be clarity on normal increases and those related to cancer to ensure the test is providing accurate information.

There is also large variance in how different cancers manifest, so there is more testing needed to ensure the results are accurate for all types of cancer.

Where Are Liquid Biopsies Available?

The results of the Oxnard and Paweletz study were so well tested that Dana-Farber/Brigham and Women’s Cancer Center began offering this kind of liquid biopsy to all their patients with this type of lung cancer.

They are the first medical facility in the country to do so and offer the testing to patients upon first diagnosis or in those who experience a relapse. The Dana-Farber/Brigham and Women’s Cancer Center liquid biopsy uses a technology called digital polymerase chain reaction (ddPCR).

Liquid biopsies are still more commonly available in research facilities than traditional care facilities. However, it’s always worth a conversation with your doctor to see if the technology is available to you and what options you may have to access it.

There are many liquid biopsy companies working to perfect the liquid biopsy procedure. The level of research and development around the technology is an indicator that liquid biopsies are the standard of the future. Here are just a few:

  • Foundation Medicine: This Massachusetts based company created the FoundationACT (Assay for Circulating Tumor DNA), which uses ctDNA samples to capture a full genomic picture when a traditional biopsy is not feasible or the tissue is not accessible to biopsy.
  • Grail: This San Francisco based company is a spin off from Illumina, a gene sequencing company, with a goal to create early detection cancer screenings through blood testing to improve the survival rate of cancer patients by making detection earlier more accessible.
  • Pathway Genomics: This San Diego based company looks for liquid biopsy biomarkers from 9 cancer causing genes.
  • Trovagene: Another San Diego based company, Trovagene, is working on a urine-based liquid biopsy called Tovera. This test detects and monitors cancer, reducing the need for repeated surgical biopsies

The Costs of Liquid Biopsies

Traditional biopsies cost upwards of $14,000, whereas liquid biopsy cost can be as low as $299.

That being said, the general cost for a liquid biopsy is still fairly high and are not yet priced at a level for standard everyday use in medical facilities.

Are Liquid Biopsies covered by insurance?

As liquid biopsies become more and more popular, it’s becoming more likely for insurance to cover the procedure. Whether or not a liquid biopsy is covered will determine wholly on where you get your care and what insurance coverage you have.

It’s best to discuss with your physician and your insurance provider to determine your eligibility.

Risks and Limitations of Liquid Biopsies

Despite the pros and cons of the liquid biopsy, the non-invasiveness of the test makes it extremely low risk. Regardless, there are risks and limitations of liquid biopsies.

One of the disadvantages of liquid biopsy is that while their use is increasing, liquid biopsies are not a standard testing procedure as of yet. Traditional tissue biopsies are still the most common test to diagnose cancer. The liquid biopsy has not replaced the tissue biopsy.

More clinical trials are needed to normalize the test. And more studies and testing is needed to prove its accuracy. It is still unclear whether the liquid biopsy collects a representative sample, which can provide accurate results about tumor DNA.

Challenges still exist in regards to test sensitivity. Tumor DNA cells are relatively few compared to the number of other similar molecules found in the blood. Because of this there are issues with the liquid biopsy’s sensitivity and accuracy.

Benefits of Liquid Biopsies

One of the biggest benefits of the liquid biopsy procedure is that it only requires a simple and relatively non-invasive blood draw to be performed.

This attribute makes it easier to perform and offers the flexibility of performing a biopsy multiple times over the course of treatment.

Changes in the composition or quantity of tumor DNA in the blood can indicate whether a tumor is growing or shrinking, and how well a treatment is or is not working, making it a crucial tool for creating more effective treatment plans.

FDA approval on Liquid Biopsies

On June 1, 2016, the U.S. Food and Drug Administration (FDA) approved the first liquid biopsy. The specific liquid biopsy test approved is for use in patients with non-small cell lung cancer to help detect a gene mutation associated with the cancer.

Since the blood biopsy for lung cancer was approved, liquid biopsy has continued to gain ground in oncology.

Other liquid biopsies are available, but the level of testing and trials around them varies. Ask your doctor for information specific to the liquid biopsy your considering.

Liquid Biopsy: Present and Future

Detection has always been at the forefront of cancer researchers’ minds. The earlier cancer is found the higher the chances are of beating it.

Unfortunately, the traditional biopsy, which tests tissue for the presence of cancer, is invasive and not always possible (e.g. when the tissue is in a place where it cannot be extracted).

The liquid biopsy represents a hope in revolutionizing how the world detects and treats cancer—potentially being able to detect before any symptoms are felt.

The road to get to today’s technology was not a short one. Researchers first had to learn where to find and how to study ctDNA. Then acknowledge that finding cancer early isn’t always enough—event early detection doesn’t equal a 100% chance of beating the disease.

The current liquid biopsy status remains on the cusp of the mainstream. As researchers try solving for pitfalls, like too little ctDNA being in certain samples they are also looking into how we might identify where cancer might be.

More research and testing is needed before liquid biopsies become the gold standard for cancer detection and treatment, but they show no signs of slowing down.

The results of liquid biopsies are well beyond promising enough to continue perfecting them. The future of liquid biopsy is applying it to patients without cancer, and feeling more and more confident about those results and the results received for those who have it.

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