Circulating Tumor Cells May Help Determine Melanoma Prognosis

Developing ways to isolate and accurately analyze circulating tumor cells (CTCs) from the blood of cancer patients with solid tumors continues to be an active area of research. Scientists have known for a long time that CTCs can be detected—the first description of CTCs in the blood of a patient with metastatic cancer was reported by Thomas Ashworth in 1869. CTCs travel in the blood as part of the metastatic process, whereby cancer spreads from one organ to another.

Researchers have been developing blood-based CTC tests to detect micro-metastases before tumor cells grow into large metastatic tumors. These tests could be used to identify early-stage cancer patients with a poor prognosis or to determine if a patient is progressing despite treatment and may need to be switched to an alternative treatment.

The trouble is that CTCs are rare in the blood and studies thus far—mostly in breast, colon, and prostate cancer patients—have had inconsistent results. A negative result is not useful and, for now, tests are not always able to detect CTCs in patients with advanced cancer. It is also not clear that all detectable CTCs are indicative of ongoing metastasis and worse prognosis. Much more research is needed to come up with reliable and reproducible ways to both capture and analyze CTCs and to fully understand the biological and clinical relevance of their presence (or absence).

So far, the only FDA-approved CTC test that both detects and analyzes CTCs is called CellSearch (made by New Jersey-based Veridex, a subsidiary of Johnson & Johnson). It is specifically approved for determining the prognosis of patients with metastatic prostate, breast, and colorectal cancers.

While CTC studies have mainly focused on epithelial malignancies like breast, prostate, and colon cancers, a recent study looked at the connection between CTCs and the prognosis of stage III melanoma patients who have a sentinel lymph node metastasis. A sentinel lymph node is the first lymph node that tumor cells are likely to spread to from the primary tumor.

Identifying high-risk patients with a positive lymph node remains difficult. A CTC test may be a way to pinpoint those patients who need more aggressive treatment, because their melanoma is more likely to spread faster. Previous melanoma CTC studies have been unable to show a clear link between the number of CTCs and stage of the melanoma.

The results of the new study, published in the Journal of Clinical Oncology (doi: 10.1200/JCO.2011.40.0887), show that the presence of CTCs can predict both recurrence-free and distant metastasis-free survival in patients with melanoma who have a positive sentinel lymph node.

The study, led by Dave Hoon of the John Wayne Cancer Institute at Saint John’s Health Center in Santa Monica, California, analyzed CTCs in blood samples from 331 patients who were deemed disease-free after surgical removal of their lymph nodes. The ability to detect CTCs ranged from about 13% to 17%. The researchers showed that, while there was no link between the presence of CTCs and other prognostic factors, detecting two of the three markers linked to CTCs was associated with worse distant metastasis-free survival that was statistically significant, as well as reduced recurrence-free survival.

The melanoma-specific CTC detection test used by the researchers looks for three markers associated with melanoma CTCs, but not normal blood cells. All three markers, MART-1, MAGE-A3, and GalNAc-T, are proteins associated with melanoma.

With more validation studies and better test sensitivity, CTC detection may be used to test patients who appear disease-free, but are at higher risk for recurrence and could benefit from earlier or more aggressive adjuvant therapy—or to monitor a patient on a specific treatment for cancer progression.