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Sentinel Lymph Node Molecular Ultrastaging in Patients With Melanoma: A Systematic Review and Meta-Analysis of Prognosis

Simone Mocellin, Dave S.B. Hoon, Pierluigi Pilati, Carlo R. Rossi, Donato Nitti

From the Surgery Branch, Department of Oncological & Surgical Sciences, University of Padova, Italy; and the Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, CA

Address reprint requests to Simone Mocellin, MD, Clinica Chirurgica II, Dipartimento di Scienze Oncologiche & Chirurgiche, Università di Padova, via Giustianiani 2, 35128 Padova, Italy; e-mail: mocellins{at}hotmail.com

Purpose Molecular biology-based ultrastaging of cancer is already part of the standard management of patients with hematologic malignancies, whereas the evidence for solid tumors is much more debated. Polymerase chain reaction (PCR) –based detection of melanoma cells in sentinel lymph nodes (SLN) of patients with melanoma represents an appealing prognostic tool. However, no consensus exists on the clinical implementation of this prognostic indicator for the management of these patients.

Methods Twenty-two studies enrolling 4,019 patients who underwent SLN biopsy for clinical stage I to II cutaneous melanoma were reviewed. Correlation of PCR status with TNM stage, disease recurrence rates, and survival was assessed by means of association statistics and formal meta-analysis, respectively.

Results PCR status correlated with both TNM stage (stage I to II v III; PCR positivity, 95.1% v 46.6%; P < .0001) and disease recurrence (PCR positive v negative; relapse rate, 16.8% v 8.7%; P < .0001). PCR positivity was also associated with worse overall (hazard ratio [HR], 5.08; 95% CI, 1.83 to 14.08; P = .002) and disease-free (HR, 3.41; 95% CI, 1.86 to 6.24; P < .0001) survival. Statistical heterogeneity was significant, underscoring the variability among overall effect estimates across studies; metaregression and subgroup analysis did not identify clear-cut sources of heterogeneity, although some study design variables were suggested as potential causes.

Conclusion PCR status of SLN appears to have a clinically valuable prognostic power in patients with melanoma. Although the heterogeneity of the studies so far published warrants caution to avoid overestimating the favorable results of pooled data, our findings strongly support additional investigation in this field.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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