Circulating Tumor Cells May Predict Melanoma Relapse

By Marilynn Larkin

February 12, 2020

NEW YORK (Reuters Health) - In patients with stage III melanoma, levels of circulating tumor cells (CTCs) may predict relapse, potentially allowing for identification of individuals who could benefit from close surveillance or adjuvant therapy, researchers say.

Five-year survival rates for these patients range from 93% with stage IIIA lesions to 32% with IIID, said Dr. Anthony Lucci of the University of Texas MD Anderson Cancer Center in Houston. Currently, he added, there are no approved blood biomarkers for risk stratification.

The study goal, he told Reuters Health by email, was to use "a simple, standardized liquid biopsy technique to look for CTCs at baseline," to determine whether they were associated with early relapse.

Dr. Lucci and colleagues assessed CTCs at first presentation in 243 patients with stage III melanoma diagnosed between 2012 -2017. The mean age was 57; 61% were men. The median follow-up was 17 months.

As reported in Clinical Cancer Research, at least one CTC was detected in 90 patients (37%), including 45 (19%) stage IIIA; 67 (28%) stage IIIB; 118 (49%) stage IIIC; and 13 (5%) stage IIID. CTC detection was not associated with substage or primary tumor characteristics.

Relapse occurred in 8% of patients with no CTCs; 22.4% with one CTC; and 24.1% with two CTCs. Overall, 25% of patients with at least three CTCs relapsed, indicating a trend to relapse with increasing numbers of CTCs. However, the numbers of patients with two or more CTCs were small.

Nonetheless, detection of at least one baseline CTC per 7.5 mL blood was significantly associated with decreased relapse-free survival at six months (hazard ratio, 3.62) and at 54 months (HR 1.69).

Dr. Lucci said, "Emerging data...suggest that liquid biopsy techniques - including measurement of circulating tumor DNA (ctDNA) looking at mutations in certain genes - can indicate when active tumor is present, and might be useful to determine response to systemic therapies."

"We are currently conducting prospective trials of serial CTC and ctDNA measurements in high-risk stage II/III melanoma patients receiving immune checkpoint inhibitors to determine if combining serial (before, during, and after immune checkpoint blockade) liquid biopsy information can provide predictive information with respect to treatment benefit," he noted.

Dr. Joseph Skitzki, Chair of the Melanoma/Sarcoma Disease Site Research Group at Roswell Park Comprehensive Cancer Center in Buffalo, New York, commented in an email to Reuters Health, "The study is impactful to the field, as there have never been any satisfactory blood markers to predict risk in these varied-risk stage III melanoma patients."

"The study was performed in a time period where completion lymphadenectomies for a positive sentinel node were standardly performed," he said, "and as this is no longer the case, predictive measures such as circulating CTC may have added value."

That said, he noted, "two most predictive variables of the primary melanoma lesion, namely thickness and ulceration, were missing in 21% and 22% of the studied patients, respectively. It is unclear if these data would have weakened the independent prognostic value of CTC."

Further, he added, "The pace of change in melanoma treatment has rapidly escalated within the last two to three years and the newer, more effective adjuvant therapies may or may not have impacted the recurrence rate reported."

"Prospective studies with serial measures of CTC over time are needed to determine if outcomes following recurrence can be improved," he concluded.

SOURCE: Clinical Cancer Research, online February 3, 2020.