In Reply

Abstract

IN REPLY:We thank Hocevar et al for their interest in our multivariate analysis of prognostic factors for patients with palpable metastatic melanoma in a single regional lymphatic basin. 1 We agree that decade of diagnosis is not a common prognostic factor for melanoma; its marginal significance in our study and its importance in the recent studies from Lasithiotakis et al 2 and Peric et al 3 thus are intriguing.However, because our study 1 focused on prognostic factors available for melanoma from an unknown primary (MUP), our findings probably should not be compared directly with any study involving a multivariate analysis that included important prognostic factors related to the primary tumor. In our study, status of the primary tumor referred to known primary melanoma versus MUP; primary tumor thickness, invasion, ulceration, and other prognostic characteristics of primary melanoma 4 were not included in the multivariate analysis. The significant covariates in our multivariate analysis were likely driven by the larger known primary melanoma cohort. In addition, our study population was a focused subset of patients with stage III melanoma with palpable nodal disease to a single nodal basin. Therefore, the significance for decade of diagnosis in this subset may not be a valid reflection of the population of patients with stage III melanoma.Hocevar et al hypothesize that melanoma has become less aggressive over time. This hypothesis cannot be discounted because none of the above-mentioned multivariate studies considered changes in and possible effects of tumor regression, mitotic rate, angiolymphatic invasion, and unidentified biologic markers. However, nonbiologic factors also must be considered in a chronologic analysis of melanoma survival, especially for a stage of disease with a 5-year overall survival rate of 24% to 70%. 5 For example, nodal tumor burden, a known prognostic factor, was not evaluated in the above studies. 2,3 Even if nodal tumor burden has decreased in recent years, is this decrease a result of the changing biology of melanoma, or is it due to earlier detection 6-8 because of increased awareness?Another unaccounted factor is the type of treatment received for stage III melanoma. Our study 1 included a cohort of patients with stage III melanoma who underwent regional lymphadenectomy for palpable nodal disease, but the studies of Lasithiotakis et al 2 and Peric et al 3 did not evaluate treatment. Although standard treatment for stage III melanoma has not changed for the last three decades, it may not be reasonable to assume that all patients underwent standard treatment. According to a recent study in the United States by Bilimoria et al, 9 only 50% of patients with sentinel node metastasis underwent complete lymph node dissection. Chronologic, demo-graphic, and geographic variations in practice patterns should be considered.Although the improved survival in more recent years could reflect a change in the biology of melanoma, other possible explanations cannot be discounted. Regardless of its ...