A tumor is not a sealed object. From early in its life, it sheds cells into the bloodstream. Most of these circulating tumor cells, or CTCs, die quickly, but a few survive the journey and settle in new organs, which is how cancer spreads. A CTC test catches these cells in an ordinary blood sample, counts them, and in some cases studies them. This article explains how the testing works, what a CTC count tells you, and the European trials in which CTC results were used to change treatment.

Part of our guide: Advanced Cancer Testing: A Guide to the Tests Beyond Standard Scans

What Circulating Tumor Cells Are

Circulating tumor cells are whole, living cancer cells traveling in the blood. They are extremely rare, on the order of a few cells among billions of blood cells in a standard tube, which is why special technology is needed to find them. They are different from circulating tumor DNA (ctDNA), which consists of fragments of DNA released by dying cancer cells. ctDNA tells you what mutations a cancer carries. CTCs are the actual cells that can seed new tumors, so they can be counted, stained for markers, grown and tested against treatments.

How CTCs Are Found

Capture by surface marker. The best-known method uses magnetic particles coated with an antibody against EpCAM, a protein on the surface of most carcinoma cells, to pull CTCs out of a 7.5 mL blood sample. The CellSearch system, which works this way, is cleared by the U.S. Food and Drug Administration for monitoring metastatic breast, prostate and colorectal cancer.

Capture by size. Cancer cells are usually larger than blood cells, so filters can separate them by size. This catches cells that have lost EpCAM, which happens when cancer cells change shape to become more mobile and invasive.

Counting all epithelial cells. Some laboratories in Germany and elsewhere in Europe count circulating epithelial tumor cells directly with laser scanning, and repeat the count over the course of treatment to see whether it is falling or rising.

These methods find different populations of cells, so results from one method cannot be compared directly with another. A patient following CTC counts over time should stay with the same method and laboratory.

Our article on the RGCC test explains one of these European laboratories in detail, and cancer testing in Germany and Greece compares the main options.

What the CTC Count Tells You

In metastatic cancer

The landmark study, published in the New England Journal of Medicine in 2004, found that women with metastatic breast cancer who had five or more CTCs in 7.5 mL of blood before starting a new treatment had shorter progression-free survival and shorter overall survival than women with fewer than five. The count after the first cycle of treatment was also predictive: a count that stayed high was an early warning that the treatment was not working.¹ Similar findings followed in prostate and colorectal cancer.

In early cancer (Germany)

The German SUCCESS trial tested more than 2,000 women with early breast cancer. Those with CTCs in the blood had a higher risk of recurrence and death, both before chemotherapy and when CTCs were still present after it.² CTCs that survive treatment are a sign that cancer cells have escaped the primary tumor and outlived the therapy, which is why they are central to the question of why cancer comes back.

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When CTC Results Changed Treatment

Knowing that a count predicts outcome is useful. The more important question is whether acting on the count improves outcome. Two European trials have tested exactly that.

The STIC CTC trial (France)

Women with hormone receptor-positive metastatic breast cancer usually start with hormone therapy, with chemotherapy reserved for more aggressive disease. In the French STIC CTC trial, the choice between hormone therapy and chemotherapy was made either by the doctor in the usual way or by the CTC count. Choosing by CTC count was as good as the doctor’s judgment overall. In the important group where the two disagreed, women whose doctor would have chosen hormone therapy but whose CTC count was high did better when they received chemotherapy.³

Our article on hormone receptor-positive breast cancer covers the treatment advances for this type.

The DETECT III trial (Germany)

Cancers change as they progress. A tumor that was HER2-negative on its original biopsy can later shed CTCs that are HER2-positive. In the German DETECT III trial, more than 2,100 women with HER2-negative metastatic breast cancer had their CTCs checked for HER2. Those with HER2-positive CTCs were randomly assigned to standard treatment with or without lapatinib, a HER2-targeted drug. The women who received lapatinib lived longer. The authors describe this as the first clinical study indicating that the characteristics of CTCs can be used to select targeted treatment.⁴

DETECT III makes a point that matters to every patient: the biopsy taken at diagnosis describes the cancer as it was then. A blood test of the cells circulating now can reveal a target the original biopsy did not show.

See our articles on HER2-positive breast cancer and Stage 4 breast cancer for the treatments these results can open up.

Clusters: Why Some CTCs Matter More

CTCs sometimes travel in small groups rather than alone. Research led by Nicola Aceto, now at ETH Zurich in Switzerland, found that these clusters are far more capable of forming metastases than single cells, with a metastatic potential estimated at 23 to 50 times higher.⁵ Some CTC tests report clusters separately, and their presence carries extra weight.

Testing CTCs Against Treatments

Because CTCs are living cells, some laboratories, mainly in Germany and Greece, go beyond counting. They isolate the cells and expose them to chemotherapy drugs, targeted drugs, repurposed drugs and natural compounds to see which ones affect them, and they study markers on the cells such as HER2, PD-L1 and markers of cancer stem cells. We explain this and the organoid-based approaches in our article on chemosensitivity testing. Published validation for blood-based drug testing is thinner than for counting, so the results are best read alongside tumor sequencing and other tests.

What CTC Testing Cannot Do

Not every cancer sheds enough CTCs to detect, especially early-stage cancers and some brain tumors. Methods that rely on EpCAM can miss cells that have changed shape to become invasive. And a single count is a snapshot; the trend across repeated tests, done by the same laboratory, is far more informative than any one value. Our book, The New Reality of Cancer, devotes a chapter to circulating tumor cells and explains how to fit CTC testing into a monitoring plan with ctDNA, imaging and tumor markers.

A ctDNA liquid biopsy reads fragments of tumor DNA in the blood instead, and the two tests complement each other.

Frequently Asked Questions

What is a CTC test?

A blood test that finds and counts living cancer cells circulating in the bloodstream. Some versions also test those cells for markers or against treatments.

What is a high CTC count?

In metastatic breast cancer tested with the CellSearch method, five or more cells in 7.5 mL of blood is the threshold linked to a worse outlook. Thresholds differ by cancer type and testing method.

What is the difference between CTCs and ctDNA?

CTCs are whole living cancer cells. ctDNA is fragments of cancer DNA released into the blood. ctDNA reveals mutations; CTCs can be counted, characterized and tested against treatments.

Can CTC results change treatment?

Yes. In the French STIC CTC trial and the German DETECT III trial, treatment chosen on the basis of CTC results improved outcomes for specific groups of women with metastatic breast cancer.

About the author. Dr. Silver, MD, graduated from Temple University School of Medicine, completed fellowship training in cardiology, and has practiced medicine for nearly fifty years. A lymphoma survivor of about twenty-five years, he is co-author, with Dr. Lindmeier, DHSc, of The New Reality of Cancer: The Science of Recovery. Read more about Dr. Silver, MD.

Research by Dr. Lindmeier, DHSc, cancer educator and co-author of The New Reality of Cancer.

This article is for general education only and is not individual medical advice. Always consult your own doctor before making any changes to your care.

For more in-depth information on this topic and many others, get our book, The New Reality of Cancer: The Science of Recovery.

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