What to Know About Liquid Biopsies for Cancer

Liquid biopsies have the potential to transform how we detect, treat, and monitor cancer. With the first FDA-approved liquid biopsy test for cancer screening now available, questions are emerging about what this means for routine care. We spoke with Chin Hur, MD, physician scientist and expert in cancer screening and prevention at the Herbert Irving Comprehensive Cancer Center (HICCC), to explore how these tests fit into the future of personalized cancer prevention, detection, and screening. 

What exactly is a liquid biopsy?

A liquid biopsy is a non-invasive blood test that analyzes substances released into the bloodstream by cancer cells, such as circulating tumor cells (CTCs), cell free DNA (cfDNA), or RNA or proteins. It's a potentially exciting alternative to traditional imaging studies or tissue biopsies, allowing us to detect and monitor cancer with a simple blood draw. 

Liquid biopsies could also help us make decisions about the best therapy for a patient based on their unique cancer type. They’re really a next step in the idea of precision cancer medicine, or precision oncology.

Which liquid biopsies have FDA approval right now?

The first liquid biopsy to receive FDA approval was CellSearch in 2013, which monitors patients with metastatic breast, colon, and prostate cancer based on the level of Circulating Tumor Cells (CTCs). In 2016, the cobas EGFR Mutation Test v2 was approved to detect key mutations in lung cancer using ctDNA, as what’s called a ‘companion diagnostic’ for treatment with Osimertinib, a lung cancer drug. Since then, it has received FDA approval as a companion diagnostic for more non-small cell lung cancer therapies. 

Then, in 2020, two major tests were approved: Guardant360 CDx and FoundationOne Liquid CDx, which both use next-generation sequencing to detect dozens or even hundreds of tumor mutations in various solid cancers. Both these tests were initially approved also as companion diagnostics for specific cancers and specific therapies, but the FDA has continued to approve additional therapeutic indications for these tests. 

Most recently, in 2024, the FDA approved Shield—the first liquid biopsy test approved for cancer screening. It screens for colorectal cancer in average-risk adults by detecting ctDNA in the blood. While a positive result still requires a follow-up colonoscopy, this marks a major step toward integrating liquid biopsy into preventive cancer care. 

What are the key limitations for liquid biopsies right now—both technical and at the population level?

Technically, the biggest challenge is sensitivity—especially in early-stage cancers, where there may not be enough tumor DNA circulating to detect. Some tests, like Shield, have strong sensitivity for colorectal cancer (~83%) but much lower detection rates for precancerous polyps (~13%). Compared to that, colonoscopies have a sensitivity rate of about 95-99%, and it allows for immediate removal of precancerous polyps. And there’s always a risk of false positives with these tests, which can lead to unnecessary follow-up testing.  

At the population level, we have to ask: are these tests cost-effective? In a study I co-led (JAMA Netw Open, 2023), we found that combining blood-based screening with colonoscopy offered some life-year benefits—but wasn’t cost-effective at current prices. That’s an important barrier if we want these tests to reach the general public.

How do liquid biopsies differ in screening vs. surveillance?

It’s a key distinction. Screening means testing people without symptoms, like using Shield to catch colorectal cancer early. Surveillance is for patients already diagnosed and refers to tracking whether cancer returns or progresses. 

Right now, liquid biopsies are strongest in surveillance and guiding treatment decisions. Tests like Guardant360 CDx can detect minimal residual disease or emerging mutations and help guide treatment over time. Screening is catching up, but we need stronger evidence on outcomes and cost before we can rely on blood-based tests across the board. 

What do you tell patients—or anyone curious—about getting a liquid biopsy right now? Is it ready for the general public?

I still recommend sticking with standard screening methods—like colonoscopy, mammograms, and low-dose CT scans for lung cancer—because they’re proven ways to detect cancer and improve outcomes. 

That said, if someone is unable or unwilling to get a colonoscopy, a test like Shield could be a reasonable alternative for colorectal cancer screening. It’s FDA-approved for that purpose, though a positive result will still need to be followed up with a colonoscopy. 

For other blood-based multi-cancer tests—like Galleri or CancerSEEK—I’d say they’re not ready for routine public use just yet. They’re promising, but we still need more evidence showing they improve outcomes, not just detect cancer. I always tell patients: it’s okay to be interested, but make informed decisions, ideally in consultation with a doctor who understands both the science and the limitations of these new tools. 

Where is the research headed—and will we eventually have a pan-cancer test?

That’s the goal: a single test that detects many cancers early.

Clinical trials like CancerSEEK and GRAIL’s Galleri are testing multi-cancer early detection (MCED) approaches, and the National Cancer Institute is sponsoring a large-scale study to evaluate these in real-world settings. 

At Columbia, researchers like Zhiguo Zhang, PhD, are developing techniques to detect cancer-specific methylation patterns in blood. In my own lab, we’re modeling how these tests perform in health systems—and whether they’re cost-effective at scale. 

We’re not at pan-cancer screening yet, but we’re getting closer. For now, liquid biopsies are a powerful tool to complement—not replace—traditional screening and monitoring strategies.