Mitotic rate in node-positive stage III melanoma: it might be as important a prognostic factor as node number

Background: Stage III melanoma is a heterogenous disease, and the number of tumor-involved lymph nodes is the most significantly unfavorable prognostic indicator for relapse and outcome. The aim of this study is to investigate the possible effects of the various clinicopathological factors on the course of node-positive stage III disease. Methods: A total of 389 node-positive stage III cutaneous melanomas were included in the study and analyzed retrospectively. All underwent pathological nodal staging by sentinel lymph node biopsy or elective lymph node dissection. Results: The group was male-dominant (59%) and the median age was 50 years. The largest group of patients was N1 (n = 221, 56.8%) followed by N2 (n = 105, 27.0%) and N3 (n = 63, 16.2%). N1 melanomas were less frequently associated with relapses than melanomas with multiple lymph node metastases (P = 0.05). The 5-year relapse-free survival rate was 37.9%. The melanomas with multiple lymph nodes metastases (P = 0.01), higher mitotic rate (P = 0.005) and ulceration (P = 0.02) had worse RFS. In the multivariate analysis only the significances of the N2-N3 stage (P = 0.016) and higher mitosis (P = 0.012) persisted. The severe lymph node metastasis (N2-N3) was associated with a higher mortality rate in comparison with the single nodal involvement (P = 0.05). The 5-year overall survival rate was 52.1%. Presence of relapse (P = 0.0001), higher mitotic rate (P = 0.03) and N2-N3 stage (P = 0.04) were inversely correlated with the overall survival. When relapse was included in the multivariate analysis, it was the only significant prognostic factor on survival (P = 0.0001), whereas mitosis became the only significant factor on survival with the exclusion of relapse from the multivariate analysis (P = 0.031). Conclusion: In node-positive stage III melanoma, tumor mitotic rate might be just as significant a prognostic indicator as the metastatic lymph node number.