Liquid Biopsy Explained: How Blood Tests Are Changing Cancer Care

A “liquid biopsy” is a minimally invasive blood test that looks for cancer-related material in the bloodstream, which can come from cancer cells or the environment around a tumor. This material may include circulating tumor DNA (ctDNA), circulating tumor cells or certain proteins. Liquid biopsy can help doctors understand the genetic makeup of a patient’s cancer, track how it changes over time and, sometimes, see whether the total amount of cancer in the body is decreasing in response to treatment.

“Liquid biopsy is the concept of being able to, via a normal blood draw, better understand the biology and abnormalities in the genetic code in your type of cancer,” says Gretel Terrero, M.D., a gastrointestinal medical oncologist at Sylvester Comprehensive Cancer Center, part of UHealth – University of Miami Health System. “I use this technology to make personalized treatment choices and, once I’ve chosen a treatment, to see if the patient’s tumor is responding favorably to that treatment.”

What liquid biopsy can — and cannot — do today.

“Liquid biopsy has drastically changed how we practice oncology, and we anticipate it will continue to improve our ability to make the best clinical decisions for each patient across their unique cancer journey,” Dr. Terrero says.

This noninvasive test is used in ways that tissue biopsy cannot be. It returns genetic information about a tumor in seven to 10 days, whereas getting that same information from tissue can take weeks. Liquid biopsy can also be performed far more frequently, and may pick up material from tumors that cannot be biopsied because they are too small or are in difficult locations.

Tissue biopsy isn’t going away, especially for diagnosis. “For solid tumors, you still need to make the tissue biopsy diagnosis — a liquid biopsy is not going to give you grade, structure and other critical diagnostic information,” says Gina D’Amato, M.D., a sarcoma medical oncologist and Sylvester’s assistant director of clinical research.

Nonetheless, Sylvester’s physician-scientists are using liquid biopsy in routine care for many cancers, and are exploring new ways to use it through clinical trials and other research.

Faster answers for patients with lung cancer

Raja Mudad, M.D., a lung cancer medical oncologist at Sylvester and medical director of Sylvester at Doral, uses liquid biopsy to plan treatment paths for his patients.

There are several mutations in lung cancer that can be targeted with specific treatments, so it’s standard to wait for DNA testing results before treatment starts. That used to mean waiting several weeks for biopsied tissue to be analyzed. “With liquid biopsy, we draw blood, and we get the results in about seven days,” Dr. Mudad says. “It enables me to give the correct treatment more quickly.”

Although results from tissue and liquid biopsy agree more than 90% of the time, some types of mutations can only be picked up from tissue. “We do both liquid and tissue biopsy, and tissue biopsy is still considered the gold standard,” Dr. Mudad says, adding that, if no mutations are picked up in the liquid, he will wait for tissue results to confirm treatment.

Dr. Mudad has used liquid biopsy to look for mutations in lung cancer since 2013, when the U.S. Food & Drug Administration approved the first such test. “In recent years, though, liquid biopsy has become more and more accurate, picking up smaller and smaller levels of cells,” he says. “As the tests become more sensitive, we’re also able to look for minimal residual disease — whether there are still circulating cancer cells for somebody who is already on treatment.”

That has meant routinely adding liquid biopsy to routine scans every six months. The liquid biopsy seems to pick up circulating cancer cells about six months before anything appears on a scan. “We’re detecting it much earlier if there is a recurrence,” Dr. Mudad says.

Targeting sarcoma through liquid biopsy

A cancer of connective tissues with more than 150 subtypes, sarcoma can originate from nearly anywhere in the body. It can also metastasize to locations that are difficult to biopsy, and metastatic lesions (tumors) will often develop mutations that make them resistant to treatment. While imaging can show tumor progression or shrinkage, it doesn’t offer detailed information about the lesions, such as whether they’ve become treatment-resistant or which mutations they may have developed.

In sarcoma, liquid biopsy holds significant potential to help clinicians tailor treatments, monitor a patient’s response, and identify resistance mutations — all with just a blood draw.

“With the information from a liquid biopsy, you could potentially skip a drug that isn’t going to work or start a drug that is going to work sooner,” Dr. D’Amato says.

This can be particularly important when a patient develops resistance to treatment.

Because different metastatic lesions can have different mutations, doctors would have to biopsy each one to know which mutations are present. “This is simply not feasible,” Dr. D’Amato says. “But with a liquid biopsy, you can conceivably detect several different mutations from several different tumors.

Dr. D’Amato and her colleagues are investigating multiple ways to use liquid biopsy to improve sarcoma care. She is researching whether biomarkers in the blood of a patient with one particular type of sarcoma can predict which treatment they will respond to. She is also testing whether a liquid biopsy already approved for a different type of cancer can measure how a patient is responding to treatment, and how it compares to the scans that are typically used.

“It’s much easier for a patient to get the blood test than a scan, and we can do the blood test more frequently,” Dr. D’Amato says. “If we find that liquid biopsy correlates with what the scans show — that would mean fewer scans, and changing their treatment sooner if it’s not working.”

Dr. D’Amato’s colleague, Jonathan Trent, M.D., Ph.D., director of Sylvester’s sarcoma molecular research program, associate director of clinical research and a professor in the Division of Medical Oncology at the University of Miami Miller School of Medicine, is investigating using liquid biopsy to detect when a patient’s cancer has become resistant to current treatment and which treatment it’s more likely to respond to. 

Advancing liquid biopsy for pancreatic and prostate cancer

Physician-researchers at Sylvester are currently studying several additional uses for liquid biopsy:

• To determine more personalized chemotherapy choices for metastatic pancreatic adenocarcinoma. Dr. Terrero, who is also Sylvester Pancreatic Cancer Research Institute’s associate director for community outreach and a K12 scholar in Sylvester’s Calabresi Clinical Oncology Research Career Development Program, is studying whether serial (repeated over time) liquid biopsies can determine, early on, which patients are not responding favorably to chemotherapy and may need to be switched to a different treatment.
• To choose the right treatment for a pancreatic tumor. Jashodep Datta, M.D., associate director for translational research at Sylvester Pancreatic Cancer Research Institute and co-leader of Sylvester’s Gastrointestinal Site Disease Group, is leading work that looks at circulating tumor DNA to find genetic patterns that suggest which patients will respond to which treatments.
• To identify which patients need aggressive prostate cancer treatment. Sanoj Punnen, M.D., co-leader of the Cancer Control Program and a professor of urologic oncology at Sylvester, and Desai Sethi Urology Institute professor of urologic oncology and vice chair of research, is leading a team developing a way to guide prostate cancer treatment by combining liquid biopsy with MRI techniques.

What about using liquid biopsy to screen for cancer in healthy people?

Only one liquid biopsy is currently approved by the Food & Drug Administration for cancer screening. Approved in 2024, this liquid biopsy screens for colorectal cancer by detecting ctDNA in blood. However, it’s less likely to detect cancer than a colonoscopy. It only detects around 13% of precancerous polyps — the growths that would be removed if detected during a colonoscopy to prevent them from becoming cancerous.

Companies are marketing “liquid biopsy” blood tests, claiming that they can screen for multiple cancer types. While these tests have gotten a lot of hype, they’re not FDA-approved, and there is no evidence that they make a difference in saving lives, Dr. Mudad says.

Overall, liquid biopsy is usually less sensitive and less precise than tissue biopsy and other screening methods. In addition, in early-stage cancer, there may not be enough circulating tumor DNA to detect.

“Liquid biopsy is sometimes a misnomer — it’s not really used to diagnose a cancer and doesn’t replace tissue biopsy,” Dr. Mudad says. “Until we have data that these tests make a difference in curing cancers, we don’t recommend routine screening with circulating tumor DNA.”

Where the science is headed

Liquid biopsy technology is improving rapidly. It’s able to detect ever-smaller levels of circulating tumor DNA and other useful markers, and integration with artificial intelligence enables analysis of increasingly complex genomic data. Researchers envision a day when liquid biopsy will be a standard part of cancer care visits.

“Our work aims to understand the dynamics, limitations and growing potential of liquid biopsy and apply these findings in our clinics so that patients live longer, better lives,” Dr. Terrero says. “The goal is to have it in our hands on a regular clinic day and be able to say to each patient, ‘I just met you, but because of your liquid biopsy results, this is the therapy I think is best for you.’”

For researchers who have spent years working around the limitations of tissue biopsy, these advances are exciting. “There are so many possibilities,” Dr. D’Amato says. “This is what I’ve been dreaming about since I started my oncology fellowship in 2001. Liquid biopsy has the potential to really personalize the treatment path for many cancer patients.”

Written by Rochelle Broder-Singer.

Tags: cancer recurrence blood test, genomic profiling cancer, liquid biopsy vs tissue biopsy, Sylvester Comprehensive Cancer Center