From the Journals

Circulating tumor cells at baseline predict recurrence in stage III melanoma



Patients with stage III melanoma who have circulating tumor cells (CTCs) at baseline may benefit from adjuvant therapy, according to investigators.

A prospective study showed that patients with at least one CTC upon first presentation had increased risks of both short-term and long-term recurrence, reported lead author Anthony Lucci, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues.

While previous studies have suggested that CTCs hold prognostic value for melanoma patients, no trials had evaluated the CellSearch CTC Test – a standardized technique approved by the Food and Drug Administration – in patients with stage III disease, the investigators wrote. Their report is in Clinical Cancer Research.

In the present study, the investigators tested the CellSearch system in 243 patients with stage III cutaneous melanoma who were treated at MD Anderson Cancer Center. Patients with uveal or mucosal melanoma, or distant metastatic disease, were excluded.

Baseline blood samples were drawn within 3 months of regional lymph node metastasis, determined by either lymphadenectomy or sentinel lymph node biopsy. CTC assay positivity required that at least one CTC was detected within a single 7.5 mL tube of blood.

Out of 243 patients, 90 (37%) had a positive test. Of these 90 patients, almost one-quarter (23%) relapsed within 6 months, compared with 8% of patients who had a negative CTC assay. Within the full follow-up period, which was as long as 64 months, 48% of patients with CTCs at baseline relapsed, compared with 37% of patients without CTCs.

Multivariable regression analysis, which was adjusted for age, sex, pathological nodal stage, Breslow thickness, ulceration, and lymphovascular invasion, showed that baseline CTC positivity was an independent risk factor for melanoma recurrence, both in the short term and the long term. Compared with patients who lacked CTCs, those who tested positive were three times as likely to have disease recurrence within 6 months (hazard ratio, 3.13; P = .018). For relapse-free survival within 54 months, this hazard ratio decreased to 2.25 (P = .006).

Although a Cochran-Armitage test suggested that recurrence risks increased with CTC count, the investigators noted that a minority of patients (17%) had two or more CTCs, and just 5% had three or more CTCs.

According to the investigators, CTCs at baseline could become the first reliable blood-based biomarker for this patient population.

“[CTCs] clearly identified a group of stage III patients at high risk for relapse,” the investigators wrote. “This would be clinically very significant as an independent risk factor to help identify the stage III patients who would benefit most from adjuvant systemic therapy.”

This study was funded by the Kiefer family, Sheila Prenowitz, the Simon and Linda Eyles Foundation, the Sam and Janna Moore family, and the Wintermann Foundation. The investigators reported no conflicts of interest.

SOURCE: Lucci et al. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-19-2670.

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