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Originally published as JCO Early Release 10.1200/JCO.2008.20.7159 on January 21 2009 © 2009 American Society of Clinical Oncology.
In ReplyNorth Atlanta Surgical Associates, Saint Joseph's Hospital of Atlanta, Atlanta, GA
Department of Surgical Oncology, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 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 al2 and Peric et al3 thus are intriguing. However, because our study1 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 melanoma4 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 detection6–8 because of increased awareness? Another unaccounted factor is the type of treatment received for stage III melanoma. Our study1 included a cohort of patients with stage III melanoma who underwent regional lymphadenectomy for palpable nodal disease, but the studies of Lasithiotakis et al2 and Peric et al3 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, demographic, 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 cause, a chronologic improvement in the survival of patients with stage III melanoma is a welcome trend. Our ongoing studies of MUP indicate that it may also apply to patients with stage IV melanoma.10 AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Lee CC, Faries MB, Wanek LA, et al: Improved survival after lymphadenectomy for nodal metastasis from an unknown primary melanoma. J Clin Oncol 26:535–541, 2008. 2. Lasithiotakis KG, Leiter U, Eigentler T, et al: Improvement of overall survival of patients with cutaneous melanoma in Germany, 1976-2001: Which factors contributed? Cancer 109:1174–1182, 2007.[CrossRef][Medline] 3. Peric B, Zgajnar J, Besic N, et al: Changing biology of cutaneous melanoma. Melanoma Res 18:225–229, 2008.[CrossRef][Medline] 4. Balch CM, Soong SJ, Gershenwald JE, et al: Prognostic factors analysis of 17,600 melanoma patients: Validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 19:3622–3634, 2001. 5. Balch CM, Buzaid AC, Soong SJ, et al: Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19:3635–3648, 2001. 6. Buettner PG, Leiter U, Eigentler TK, et al: Development of prognostic factors and survival in cutaneous melanoma over 25 years: An analysis of the Central Malignant Melanoma Registry of the German Dermatological Society. Cancer 103:616–624, 2005.[CrossRef][Medline] 7. Garbe C, McLeod GR, Buettner PG: Time trends of cutaneous melanoma in Queensland, Australia and Central Europe. Cancer 89:1269–1278, 2000.[CrossRef][Medline] 8. Jemal A, Devesa SS, Hartge P, et al: Recent trends in cutaneous melanoma incidence among whites in the United States. J Natl Cancer Inst 93:678–683, 2001. 9. Bilimoria KY, Balch CM, Bentrem DJ, et al: Complete lymph node dissection for sentinel node-positive melanoma: Assessment of practice patterns in the United States. Ann Surg Oncol 15:1566–1576, 2008.[CrossRef][Medline] 10. Lee CC, Faries MB, Wanek LA, et al: Improved survival for stage IV melanoma from an unknown primary site. J Clin Oncol 26:490s; 2008 (suppl) abstr 9031.
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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