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The Prognostic Value of Circulating Tumor Cells in Patients with Melanoma: A Systematic Review and Meta-analysis

Authors' Affiliations: ¹ Surgery Branch, Department of Oncological and Surgical Sciences, University of Padova, Padua; ² Instituto Oncologic Veneto, Padova, Italy; ³ Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California; and ⁴ Statistics Center for Biomedical Sciences, San Raffaele University, Milan, Italy

Requests for reprints: Simone Mocellin, Clinica Chirurgica II Dipartimento di Scienze Oncologiche & Chirurgiche, Università di Padova, via Giustianiani 2, 35128 Padua, Italy. Phone: 39-049-8211851; Fax: 39-049-651891; E-mail: mocellins{at}hotmail.com.

Background: The detection of circulating tumor cells (CTC) in patients with melanoma represents an appealing prognostic tool, but no consensus exists on this topic. We aimed to comprehensively and quantitatively summarize the evidence for the use of CTC to predict patients' clinical outcome.

Methods: Fifty-three studies enrolling 5,433 patients were reviewed. Correlation of CTC status with tumor-node-metastasis disease stage and patients' overall (OS) and progression-free (PFS) survival was assessed by means of association statistics and meta-analysis, respectively.

Results: CTC status correlated with both tumor-node-metastasis stage (stage I, 32%; stage II, 41.7%; stage III, 41.1%; stage IV, 47.4%; P_trend < 0.0001) and survival (OS: hazard ratio, 2.42; 95% confidence interval, 1.7-3.45, P < 0.0001; PFS: hazard ratio, 2.45; 95% confidence interval, 1.78-3.38; P < 0.0001). However, statistical heterogeneity was significant for both OS and PFS, likely underscoring the wide variability in study design. Furthermore, CTC positivity rates in early stages were higher and in the metastatic setting were lower than expected, which indicates an unsatisfactory accuracy of currently available CTC detection assays.

Conclusions: Our findings suggest that CTC might have a clinically valuable prognostic power in patients with melanoma. However, the heterogeneity of the studies thus far published warrants caution not to overestimate the favorable results of pooled data.

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