CTCs Found to Be Predictive for Recurrence and Survival in Melanoma Patients

Dave S.B. Hoon, PhD

Circulating tumor cells (CTCs) can be a predictive blood biomarker for recurrence and survival in patients with stage III melanoma and may help identify who will benefit from aggressive adjuvant therapy, according to a new study led by Dave S.B. Hoon, PhD, Department of Molecular Oncology, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, California.

CTCs break off from the tumor and flow through the bloodstream, and they have demonstrated strong prognostic value in various malignancies, including breast and colorectal cancer, as well as melanoma.

For this study, Hoon et al tested whether detection of CTCs in patients with stage III melanoma after sentinel lymph node biopsy and complete lymphadenectomy (CLND) might help to identify patients at high risk of recurrence. The investigators used blood samples from a subset of patients (n = 320) who were clinically disease-free after CLND before enrolling in the phase III MMAIT study, an international, multicenter, randomized trial that tested the efficacy of adjuvant melanoma vaccine plus bacillus Calmette-Guérin (BCG) versus BCG plus placebo.

The patients’ blood samples were assessed for MART-1, MAGE-A3, and GalNAc-T, using a multimarker reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) assay. These three biomarkers have been used previously to detect CTCs in the blood. Cox regression analyses were used to evaluate the prognostic significance of these CTC biomarkers for disease recurrence and melanoma-specific survival (MSS). Patients were then classified by zero to one positive biomarker (n = 288) and two or more positive biomarkers (n = 32).

Detection frequency ranged from 13.4% to 17.5%: MART-1, 44 (13.8%); MAGE-A3, 43 (13.4%); and GalNAc-T, 56 (17.5%).

The rate of distant metastasis disease-free survival (DM-DFS) for all patients at 3 years was 75.3%; at 5 years it was 66.0%. At pretreatment, no specific CTC biomarker demonstrated a significant association with distant recurrence.

At a median follow-up of 51.7 months, 15 of 32 patients (47%) with two or more positive CTC biomarkers in their pretreatment blood specimen had distant recurrence versus 28% of patients in the zero-to-one group (82 of 288 patients). DM-DFS also was significantly higher in the zero-to-one group at 3 and 5 years (77.3% and 67.5%, respectively) than for those in the two or more group at those same intervals (57.3% and 52.6%, respectively; P = .025).

The investigators found that the presence of two or more positive CTC biomarkers proved to be a significant prognostic factor in recurrence-free survival (RFS). MSS rates also were impacted by the number of CTC biomarkers, with patients in the zero-to-one group having significantly higher MSS (83.8% at 3 years; 73.4% at 5 years), compared with those in the two or more group at 3 and 5 years (62.8% and 58.9%, respectively; P = .031).

Hoon et al noted that the results, “demonstrated that CTC detected after locoregional surgical treatment and before adjuvant therapy is effective in predicting RFS, DM-DFS, and MSS,” and thus should assist in determining which patients are likely to benefit from new therapeutic agents in development. “Given these significant results, CTC biomarker status may be useful in stratifying high-relapse—risk patients for adjuvant therapy.”

Hoshimoto S, Shingai T, Morton DL, et al. Association between circulating tumor cells and prognosis in patients with stage III melanoma with sentinel lymph node metastasis in a phase III international multicenter trial. J Clin Oncol. 2012;30(31):3819-3826.