Multivariate Analysis of Prognostic Factors Among 2,313 Patients With Stage III Melanoma: Comparison of Nodal Micrometastases Versus Macrometastases

Abstract

A B S T R A C T PurposeTo determine the survival rates and independent predictors of survival using a contemporary international cohort of patients with stage III melanoma. Patients and MethodsComplete clinicopathologic and follow-up data were available for 2,313 patients with stage III disease in an updated and expanded American Joint Committee on Cancer (AJCC) melanoma staging database. Kaplan-Meier and Cox multivariate survival analyses were performed. ResultsAmong all 2,313 patients with stage III disease, 81% had micrometastases, and 19% had clinically detectable macrometastases. The 5-year overall survival was 63%; it was 67% for patients with nodal micrometastases, and it was 43% for those with nodal macrometastases (P Ͻ .001). Tremendous heterogeneity in survival was observed, particularly in the microscopically detected nodal metastasis subset (from 23% to 87% for 5-year survival). Multivariate analysis demonstrated that in patients with nodal micrometastases, number of tumor-containing lymph nodes, primary tumor thickness, patient age, ulceration, and anatomic site of the primary independently predicted survival (all P Ͻ .01). When added to the model, primary tumor mitotic rate was the second-most powerful predictor of survival after the number of tumor-containing nodes. In contrast, for patients with nodal macrometastases, the number of tumor-containing nodes, primary ulceration, and patient age independently predicted survival (P Ͻ .01). ConclusionIn this multi-institutional analysis, we demonstrated remarkable heterogeneity of prognosis among patients with stage III melanoma, especially among those with nodal micrometastases. These results should be incorporated into the design and interpretation of future clinical trials involving patients with stage III melanoma.

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“…1 Therefore, there is a critical need to identify clinically significant biomarkers to delineate those patients at highest risk for an aggressive disease course. The 2009 AJCC staging system for melanoma determined that the primary tumor (pT) should be classified according to tumor thickness (mm) with further refinement according to the presence of ulceration (for all tumors) or dermal mitotic figures (for tumors r1.0 mm).…”

Chinese Guidelines on the Diagnosis and Treatment of Melanoma (2015 Edition)

“…For patients with positive sentinel lymph nodes (SLNs), the number of positive lymph nodes as well as the tumor load of SLNs, thickness of primary lesion, MR, ulceration, and age is the most important factors in predicting survival. For patients with clinically positive lymph nodes (physical examination or imaging shows the presence of swollen lymph nodes), the prognostic factors include the number of lymph nodes, ulceration of primary lesion, and age (36). All these information must be included in the pathology report.…”