From the time a malignant tumor reaches 2mm in diameter, it needs its own blood supply to ensure that enough oxygen and nutrients reach the cells to enable their continued growth. From this point, it becomes possible for malignant cells to enter the bloodstream. Circulating tumor cells (CTCs) are a subpopulation of tumor cells derived from the primary cancer site which have entered the blood stream.

Many will be destroyed by the body's immune system, but the most resilient cells will persist. These are called circulating tumor cells. They have metastatic potential as they can settle and grow in distant organs, which is the basis of metastatic invasion. These cells also have "stem-cell like properties" because they can both generate new cells, and reproduce themselves.

The presence of CTCs doesn't automatically mean there is metastatic spread, but it indicates that this potential exists. The micro-environment in the body, plus the individual's immune system, as well as a range of other factors determine whether these cells activate and generate metastatic disease, or remain quiescent. They can remain quiescent for years. When a cancer relapses many years after the primary tumor was diagnosed and treated, it is because some cancer cells were left behind with the potential to re-activate and generate new disease.

"CTCs have a wealth of clinical information in the evaluation of tumor progression, prediction of long term prognosis, identification of patients who are likely to respond to treatment or curative intent, and assessment of likelihood of recurrence." [1] Cell counts can detect as low as 1 cell per ml. For a tumor to be visible on a scan, between 109 - 1012 cells must be present.

In terms of its potential to metastasize and grow, CTCs are essentially the "engine" of the cancer. They are increasingly of interest to researchers and clinicians in hopes that they will become the target for future treatments. A growing number of clinical trials have been conducted, in which CTC counts were correlated with the clinical outcome of patients involved. There is therefore some guidance about what each specific cell count means, but there are no formal reference ranges yet due to the lack of formal clinical validation of these tests. It is clear, however, that the number of CTCs detected in a standardized blood sample does provide information about prognosis.

CTCs can also be tested to see which treatments they are sensitive to. This is chemosensitivity testing, and it is an important part of personalized cancer therapy.

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1. Panteleakou, Z., et al., Detection of circulating tumor cells in prostate cancer patients:methodological pitfalls and clinical relevance. Mol Med, 2009. 15(3-4): p. 101-14.