Extracapsular Spread in Melanoma Lymphadenopathy: Prognostic Implications, Classification, and Management.

Background: Extracapsular spread (ECS) is recognized to be a high-risk factor in melanoma patients with macrometastatic (N+) nodal disease; however, ECS risk in sentinel lymph node (SLN) biopsy, micrometastatic stage III disease is ambiguous.

Objective: The aim of this study was to examine ECS incidence and its prognostic significance.

Methods: A two-center, retrospective analysis of all patients with micro/macrometastatic lymphadenopathy undergoing nodal surgery from 2008 to 2014 was performed. Patient demographics, tumor characteristics, nodal ECS status, and patient outcomes were collected.

Results: Overall, 515 patients with nodal disease were identified (males/females = 277/238); median age was 63 years (range 17-94). There was an increased frequency of ECS disease in N+ disease compared with SLN+ disease (52.4% vs. 16.2%; p < 0.0001). The absolute disease-specific survival (DSS) difference for SLN+ patients was approximately 30% at 10 years (66.2% vs. 37.2%; p < 0.0001), and the prognosis of SLN+/ECS+ patients was identical to N+/ECS- patients. Multivariate analysis demonstrated that ECS status was an independent prognostic indicator for DSS (hazard ratio 2.47, 95% confidence interval 1.87-3.26; p < 0.0001) in patients with SLN+ disease. There were significant differences in nodal burden according to ECS status between the SLN+ and N+ subgroups suggestive of differing biology in ECS+ tumors.

Conclusion: We found that ECS is a significant DSS, progression-free survival, and overall survival indicator in SLN+ and N+ disease. We demonstrated that ECS upstages stage III disease, similar to ulceration in primary melanoma (stage I/II disease). A simplified staging system substituting ECS for N stage accurately stages patients according to prognosis.