Circulating Tumor Cells Useful for Identification of Potential Melanoma Relapse

A recent study determined circulating tumor cells were associated with melanoma relapse, suggesting that this form of liquid biopsy could help identify patients who would benefit from adjuvant therapy.

Circulating tumor cells (CTCs) were found to be independently associated with melanoma relapse, which suggests CTC assessment could be useful to identify patients at risk of relapse who could benefit from a more aggressive therapy, according to a recent study published in Clinical Cancer Research.1-2

One or more CTCs, a form of liquid biopsy, were found in the baseline blood sample in 37% of patients. Further, 14% of patients experienced disease relapse within 6 months of the baseline CTC measurement.

“These results suggest that CTC assessment at first presentation of node-positive melanoma may be useful for the early identification of stage III patients who are at high risk for disease relapse,” said lead investigator Anthony Lucci, MD, from the Department of breast surgical oncology at The University of Texas MD Anderson, in an interview. “We believe that identification of high-risk patients should allow optimal use of effective adjuvant immunotherapies.”

The prospective study recruited 243 patients of stage III cutaneous melanoma with patients in different sub-stages of node-positive melanoma. Of the 243 patients, 45 had stage IIIA disease, 67 had stage IIIB disease, 118 had stage IIIC disease, and 13 patients had stage IIID disease. The goal of the study was to utilize a liquid biopsy technique to look for CTCs at baseline presentation of patients.

As a result, CTC detection was not associated with stage designation or primary tumor characteristics. The detection of 1 or more CTCs was associated with a decreased 6-month relapse-free survival (hazard ratio (HR), 3.62; 95% CI, 1.78-7.36; P <0.0001) and 54-month relapse-free survival (HR 1.69; 95% CI, 1.13-2.54; P = 0.01).

“We were not certain we could routinely identify CTCs in patients with node-positive melanoma, as previous studies were performed with patients who already had metastatic (Stage IV) disease,” said Lucci. “We were surprised when we were able to identify CTCs in over one-third of the node-positive patients.”

As Lucci describes, the goal is that liquid biopsy information will be utilized in the near future to guide the treatment of patients with melanoma. He believes this data will help determine who will benefit the most from adjuvant therapies, in turn avoiding unnecessary treatments and toxicities to those who will not benefit.

Further, in the near future, the team hopes liquid biopsy can be a more effective means of monitoring how a patient responds to therapy. Lucci hypothesizes that “future liquid biopsy techniques will prove to be more sensitive and cost-effective monitoring techniques than routine imaging such as PET or CT scans.”

“CTCs provided independent information on likelihood of relapse, even when accounting for different sub-stages, or standard clinical and pathologic factors used in the clinic for treatment decision-making, said Lucci. “This finding supports future use of liquid biopsy in the clinic, since it appears to add information on disease relapse risk that one simply could not get from clinical information alone. Larger, prospective studies will confirm the utility of liquid biopsy in patient management, but this was an important first step.”

A limitation of the study was that tumor molecular profiling was not routinely performed for stage III patients at the time of patient recruitment, meaning the investigators were not able to determine if CTC detection was associated with any specific tumor mutation or molecular signature. Further, the researchers were not able to determine whether current aggressive therapies effect CTC detection because effective checkpoint blockades and targeted therapy regimens were not deployed during the time of the study.

Going forward, the researchers hope liquid biopsy can provide valuable information as to who is at high-risk of relapse, as well as provide predictive information regarding potential therapies and their effectiveness for patients.


1. Lucci A, Hall CS, Patel SP, et al. Circulating tumor cells and early relapse in node-positive melanoma. Clinical Cancer Research. DOI: 10.1158/1078-0432.CCR-19-2670.

2. Study demonstrates liquid biopsy as effective predictor of stage III melanoma relapse and treatment [news release]. Houston, Texas. Published February 3, 2020. Accessed February 4, 2020.