Circulating Tumor Cells and Early Relapse in Node-positive Melanoma

Abstract

Purpose: There is a need for sensitive, reproducible biomarkers for patients with stage III melanoma to guide clinical decision making. Circulating tumor cells (CTCs) can be detected in patients with melanoma; however, there are limited data regarding their significance in stage III disease. The aim of this study was to determine whether CTCs are associated with early relapse in stage III melanoma.Experimental Design: We prospectively assessed CTCs at first presentation in clinic (baseline) for 243 patients with stage III melanoma. CTCs were measured using the CellSearch System. Relapse-free survival (RFS) was compared between patients with one or more baseline CTC versus those with no CTCs. Log-rank test and Cox regression analysis were applied to establish associations of CTCs with RFS.Results: At least one baseline CTC was identified in 90 of 243 (37%) patients. Forty-five (19%), 67 (28%), 118 (49%), and 13 (5%) patients were stage IIIA, IIIB, IIIC, or IIID, respectively. CTC detection was not associated with substage, or primary tumor characteristics. Multivariable analysis demonstrated that the detection of ≥1 baseline CTC was significantly associated with decreased 6-month RFS [log-rank, P < 0.0001; HR, 3.62, 95% confidence interval (CI), 1.78-7.36; P < 0.0001] and 54-month RFS (log-rank, P ¼ 0.01; HR, 1.69; 95% CI, 1.13-2.54; P ¼ 0.01).Conclusions: ≥1 CTC was independently associated with melanoma relapse, suggesting that CTC assessment may be useful to identify patients at risk for relapse who could derive benefit from adjuvant therapy.

The Role of Proteoglycans in Cancer Metastasis and Circulating Tumor Cell Analysis

“…In a study of 93 stage IV patients, Hall et al (2018) found that presence of CTCs at baseline was associated with shorter progressionfree survival after 6 months compared to CTC-negative patients. Later, the same research group showed that CTC-positivity at baseline for stage III patients (n = 243) was an independent predictor of relapse-free survival within 6 and 54 months (Lucci et al, 2020). The CTC levels in these studies were not associated with primary tumor characteristics, such as ulcerations, tumor thickness, and mutational status.…”

“…Interestingly, CTC-negative melanoma patients have been found to have better progression-free or relapse-free survival compared to CTC-positive patients (Hall et al, 2018;Lucci et al, 2020). However, a significant proportion of late-stage melanoma patients still appear to have no CTCs detectable by CellSearch R (Rao et al, 2011;Roland et al, 2015;Hall et al, 2018).…”

Predicting Metastasis in Melanoma by Enumerating Circulating Tumor Cells Using Photoacoustic Flow Cytometry

“…A recent study by Lucci et al reported a strong correlation of CTCs in melanoma patients and relapse of disease. This study was conducted with the CellSearch system, and it was found that more than one CTC in baseline blood samples of recently surgically treated 243 Stage III melanoma patients correlated highly with advancement toward metastasis [3]. Their work paralleled our own findings, though ours were performed on serial sampling of blood from patients.…”

Photoacoustic detection of circulating melanoma cells in late stage patients

“…In particular, the signi¯cance of detecting CMCs and their relationship to developing metastatic disease is supported by other technologies. 37 Photoacoustic°o w cytometry has powerful, unique capabilities tō nd rare CMCs in the blood of melanoma patients. We are continuing our studies to develop a predictive system for metastasis based on our Stage III data.…”