CTC Count: Liquid Biopsy?

David J. Kerr, MD


March 19, 2012

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Hello. I'm David Kerr. I'm a Professor of Cancer Medicine at the University of Oxford and Past President of the European Society of Medical Oncology. The first description of circulating tumor cells was made in 1869, but only relatively recently, because of significant technical steps forward in regard to how we actually measure and assess the number of circulating tumor cells, has it come anywhere near entering clinical practice.

There was a very interesting article in the Annals of Oncology by Professor Pierga from Institut Curie in Paris.[1] He designed, rather beautifully, a prospective trial aimed to determine the prognostic significance of circulating tumor cells in patients with advanced and metastatic breast cancer who were receiving primary chemotherapy.

The method used was the CellSearch® method. This is a full cytometric assay based on epithelial determinants that are expressed by breast cancer cells found in the circulation. It's a way of separating the epithelial cell, a needle in a haystack, from the surrounding milieu of billions of white blood cells. They studied a cohort of about 265 patients. They took serum samples in which they used this technique to measure the number of circulating tumor cells. It was a very well-designed study. They found that there was a very significant prognostic effect in patients with 1 or more circulating tumor cells (65% of the patient population), [demonstrated by] a very strong prognostic correlation with progression-free survival.

However, when a threshold of more than 5 circulating tumor cells was found in 7.5 mL of blood (the standard threshold that is accepted by the community), there was a very significant prognostic correlation not only with progression-free survival but also with overall survival. They showed that there were strong correlations between the burden of circulating tumor cells and performance status, tumor burden, bone and liver metastasis, and also a correlation with other serum markers like CA 15-3 and carcinoembryonic antigen.

This is probably the largest and best prospective study looking at prognostic factors showing that the circulating tumor cell count is important. It is difficult to be absolutely certain yet about its predictive value. Because they took serial samples, they noted that there was a decrease in the number of circulating tumor cells. For example, in patients with more than 5 circulating tumor cells at baseline, by the time they did a couple of cycles of chemotherapy, the number had fallen significantly in more than half of the patients. To be able to determine the predictive nature of [circulating tumor cells], we would need a larger study that is powered in quite a different way, and that question is being answered in 2 prospective randomized trials. We await the results with interest.

I think circulating tumor cells as a prognostic marker is here to stay. Clearly, we are starting to explore whether we could make, in effect, a liquid biopsy. Could we take circulating tumor cells and sort them according to expression of a biomarker that may account for sensitivity to chemotherapy? The jury is still out on that, but interesting numbers of biomarker-associated drugs are being introduced.

It will be interesting to see whether, rather than having to do a biopsy of a metastatic deposit in the liver, for example, the circulating tumor cells are reflective of the general biology of the cancer.

I think this will creep its way into the consciousness of general clinical practice. As always, I would be very happy to answer any questions from all of you Medscapers out there. Thanks again for listening.


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