Liquid Biopsy: How Circulating Tumor DNA Is Changing Cancer Monitoring

Martin Kelly Jan 19, 2026 0

Imagine knowing if your cancer treatment is working before your next scan shows any change. No needles into your lung. No surgery to pull out tissue. Just a simple blood draw that tells you if the tumor is shrinking, growing, or hiding mutations that make drugs useless. This isn’t science fiction. It’s happening right now in clinics-from Sydney to San Francisco-using something called circulating tumor DNA, or ctDNA.

What Is Liquid Biopsy, Really?

A liquid biopsy isn’t a biopsy in the traditional sense. You don’t cut into anything. Instead, it’s a blood test that looks for tiny fragments of DNA shed by cancer cells into your bloodstream. These fragments are called circulating tumor DNA, or ctDNA. When cancer cells die, they break apart and release pieces of their DNA into the blood. Scientists can now fish out these pieces, read their genetic code, and learn what’s happening inside the tumor-even if it’s deep in the liver, lung, or bone.

This approach started gaining real traction around 2019, but the idea of finding cancer clues in blood goes back decades. Early research looked for whole cancer cells floating in blood, but those are rare. ctDNA, on the other hand, is more abundant and easier to detect with modern tools. Today, liquid biopsy doesn’t just look at ctDNA. It also checks for tumor-derived RNA, proteins, and even changes in how DNA is packaged (methylation patterns). But ctDNA remains the star of the show.

Why It Beats Traditional Biopsies

Traditional tissue biopsies are painful, risky, and often impossible. Needing to get a sample from a tumor near the spine? That’s a dangerous procedure. A tumor in the pancreas? Hard to reach. And even if you get a sample, it’s just one piece of the tumor. Cancer isn’t uniform-it changes across different parts of the body. A biopsy from one spot might miss the most dangerous mutation hiding elsewhere.

Liquid biopsy fixes this. A single blood draw captures DNA from tumors all over the body. It gives a full picture, not a snapshot. Studies show single-site biopsies miss up to 30% of key mutations because of this spatial variation. Liquid biopsy catches them.

It’s also repeatable. You can’t do a tissue biopsy every month. But you can draw blood every 4 to 8 weeks during treatment. That means doctors can see if a drug is working within weeks-not months. If resistance is building, they can switch therapies before the cancer spreads further. In lung cancer, ctDNA testing has found targetable EGFR mutations in 92% of cases where tissue was too small or damaged to test. That’s life-changing.

How It Works: The Science Behind the Blood Test

Not all blood tests are created equal. Detecting ctDNA is like finding one wrong letter in a library of books. The cancer DNA makes up less than 0.1% of all free DNA in your blood. To find it, labs use ultra-sensitive tools.

The most common methods are:

Digital droplet PCR (ddPCR): Splits blood into thousands of tiny droplets and counts mutant DNA molecules. Can detect one cancer mutation in 10,000 normal ones.
Next-generation sequencing (NGS): Reads millions of DNA fragments at once. Can screen for dozens of cancer genes at the same time.
Methylation analysis: Looks at chemical tags on DNA that turn genes on or off. Cancer DNA has abnormal methylation patterns-even before mutations appear. Adding this boosts detection by 20-30%.

There’s also a smarter approach called “tumor-informed” testing. First, they sequence the tumor from a past biopsy. Then they build a custom test to look for those exact mutations in the blood. This cuts down false alarms and boosts accuracy.

And it’s not just about mutations. The size of DNA fragments, how they’re wrapped around proteins (nucleosome patterns), and even how they break apart tell scientists where the tumor came from. A lung cancer fragment looks different from a colon cancer one. This helps even when the origin is unknown.

A patient receiving a blood draw while holographic tumor fragments dissolve above them.

Where It’s Making the Biggest Difference

Liquid biopsy isn’t useful for every cancer. It shines where tumors shed lots of DNA.

Non-small cell lung cancer: NCCN guidelines now say liquid biopsy is an option for first-line EGFR, ALK, ROS1 testing when tissue is limited. About 35% of metastatic lung cancer patients get tested this way.
Colorectal cancer: ctDNA can detect recurrence after surgery with 85-90% accuracy-up to 11 months before scans show anything.
Breast cancer: Used to monitor treatment response and spot ESR1 mutations that make hormone therapy fail.
Melanoma and ovarian cancer: Tracking BRAF or BRCA mutations in real time helps adjust targeted therapies.

For patients with metastatic disease, liquid biopsy has cut the need for repeat tissue biopsies by 25-30%. That means fewer complications, less pain, and more data.

The Limits: When It Falls Short

It’s not magic. Liquid biopsy has blind spots.

Early-stage cancers: Only 50-70% of stage I tumors shed enough ctDNA to be detected. That’s why it’s not yet used for screening healthy people.
Brain tumors: The blood-brain barrier traps most ctDNA. Detection rates can be under 40%.
Slow-growing cancers: Like some prostate or thyroid cancers, they release little DNA. Blood tests often come back negative even when the tumor is active.
Clonal hematopoiesis: As we age, blood cells pick up random mutations. These aren’t cancer-but they can look like it. About 10-15% of patients over 65 have this, and labs must filter it out.
Variants of unknown significance: About 15-20% of reports find genetic changes that doctors don’t yet understand. This creates anxiety and confusion.

And accuracy varies. One lab’s test might detect a mutation another misses. Standardization is still a mess. A 2023 multicenter study found up to 25% of results differed between labs using the same sample.

An AI interface analyzing colored DNA strands from multiple cancers with flowing algorithms.

Real Impact: What It’s Doing in Clinics Today

At MD Anderson, liquid biopsies are now part of 35-40% of phase I clinical trials. Oncologists use them to:

Confirm minimal residual disease after surgery-meaning no cancer left behind.
Spot resistance mutations months before tumors grow on a CT scan.
Identify pseudo-progression: when immunotherapy makes tumors look bigger on scans, but they’re actually dying. ctDNA drops in these cases, confirming the treatment is working.

One patient in Sydney, diagnosed with stage IV lung cancer, had a liquid biopsy after her first round of chemo. Her ctDNA levels dropped 90% in 3 weeks. Her oncologist skipped a CT scan and gave her another round of the same drug. Three months later, her scan showed no growth. The blood test had told them the truth earlier.

Another patient had surgery for colon cancer. His ctDNA stayed negative for 10 months. Then, it spiked. No signs on scans. His doctor started a new drug. Six months later, his scan showed a tiny spot in the liver-exactly where the ctDNA had signaled trouble.

The Future: What’s Coming Next

The next five years will change everything.

Multi-analyte tests: Combining ctDNA, methylation, fragment size, and RNA into one test. Early results show sensitivity for stage I cancers rising to over 95%.
AI-powered analysis: Machine learning is being trained to spot cancer patterns in DNA fragmentation. At MD Anderson, AI boosted diagnostic accuracy by 15-20% in early trials.
Tumor-agnostic screening: Tests that don’t need to know where the cancer started. Just detect cancer, then figure out the source.
Lower detection limits: Labs are pushing to find one cancer molecule in 100,000 normal ones-enough to catch recurrence even earlier.

Regulatory approval is accelerating. The FDA has approved 12 liquid biopsy tests since 2020, including Guardant360 CDx and FoundationOne Liquid CDx. ASCO updated its 2023 guidelines to recommend liquid biopsy for advanced lung cancer when tissue isn’t available.

The global market is exploding-from $4.4 billion in 2022 to an expected $19.5 billion by 2030. But cost and access remain barriers. Only 60-70% of academic centers offer it. Community clinics? Just 25-30%.

What This Means for You

If you or someone you know has advanced cancer, ask your oncologist: “Can we use a liquid biopsy to monitor treatment?” It’s not a replacement for imaging or tissue diagnosis-but it’s a powerful companion. It gives you faster answers, fewer invasive tests, and the chance to switch therapies before it’s too late.

It won’t replace mammograms or colonoscopies for screening. But for monitoring, it’s already the future. And in five years, it may be the standard.

Is liquid biopsy better than a tissue biopsy?

It’s not better-it’s different. Tissue biopsies are still needed for initial diagnosis and to confirm cancer type. But for monitoring, liquid biopsy wins. It’s less risky, gives a full picture of the tumor’s genetics, and can be done repeatedly. Think of it as a real-time update, while tissue biopsy is the original report.

Can liquid biopsy detect cancer early?

For early-stage cancers, sensitivity is still limited-around 50-70% for stage I. It’s not reliable enough for population-wide screening yet. But for high-risk people-like those with BRCA mutations or a strong family history-it’s being tested in trials. Methylation-based tests show the most promise here, possibly catching cancer before it’s visible on scans.

How often should liquid biopsy be done?

During active treatment, every 4-8 weeks is common. After treatment ends, every 3-6 months for surveillance. But it depends on the cancer type. Lung cancer patients may be tested monthly during chemo. Someone with slow-growing prostate cancer might only get tested once a year. Your doctor will decide based on your risk and treatment plan.

Does insurance cover liquid biopsy?

In many countries, including Australia and the U.S., insurance covers liquid biopsy for advanced cancers when tissue isn’t available or for monitoring treatment response. Medicare and private insurers typically cover FDA-approved tests like Guardant360 or FoundationOne Liquid CDx. But coverage varies-always check with your provider and oncologist.

What if my liquid biopsy result is positive but my scan is normal?

This happens. ctDNA can detect cancer cells before they form visible tumors. A positive result with a normal scan might mean minimal residual disease-tiny amounts of cancer left after treatment. In that case, your doctor may recommend earlier or more aggressive therapy. It’s not a false alarm-it’s an early warning. Follow up with your oncologist to understand the next steps.

Can liquid biopsy replace imaging like CT or PET scans?

No-not yet. Imaging shows where the cancer is and how big it is. Liquid biopsy tells you what’s happening genetically. You need both. But liquid biopsy can reduce how often you need scans. If ctDNA stays low, you might skip a scan. If it spikes, your doctor knows to scan immediately. Together, they give a fuller picture.