The Impact of Primary Melanoma Thickness and Microscopic Tumor Burden in Sentinel Lymph Nodes on Melanoma Patient Survival

Abstract

The primary objectives of this work are to (1) quantitate tumor burden in sentinel lymph nodes (SLNs), and (2) assess the independent contributions of SLN tumor burden and primary melanoma thickness (PMT) with respect to progression-free survival (PFS) and overall survival (OS). Sixty-three patients (41 male and 22 female) with one or more positive SLNs were available for review in this study, with median follow-up of 6.8 years. PMT was measured and SLN metastases were assessed for size, as maximum metastasis size (MMS) in mm, by hematoxylin and eosin (H&E) and immunohistochemistry (S100 and HMB45). PFS and OS were calculated from time of SLN resection until melanoma recurrence or death. Univariate and multivariate analyses and trend test were performed. Kaplan-Meier estimates of PFS and OS differed significantly by MMS (log-rank P = 0.031 for PFS and P = 0.016 for OS) and PMT (log-rank P = 0.036 for PFS and P < 0.001 for OS). After adjusting for age and gender, the hazard ratio (HR) associated with MMS was 1.09 per mm increase (P = 0.05) for PFS, and 6.30 (P = 0.014) and 5.41 (P = 0.048) for OS in patients, respectively, with MMS of 0.6-5.5 mm and MMS ≥5.5 mm compared with those with MMS <0.6 mm. When patients were stratified by their tumor characteristics of PMT, the risk for disease progression and worse OS was substantially higher for the group with PMT ≥ 4.5 mm (HR = 13.10 and P = 0.022 for PFS; HR = 17.26 and P < 0.001 for OS) relative to the baseline group with PMT <1.6 mm. All patients had completion lymph node dissection (CLND) except for four patients. Patients with positive CLND (14, 22.2%) showed significant worse PFS (P = 0.002) and OS (P = 0.0003) than the negative CLND group (45, 71.4%). PMT and MMS were independently prognostic of PFS and OS in melanoma patients. Patients with negative CLND had significantly better PFS and OS than those with positive CLND.