Thick primary melanoma has a heterogeneous tumor biology: an institutional series

<p>Abstract</p> <p>Background</p> <p>Thick melanomas (TM) ≥4 mm have a high risk for nodal and distant metastases. Optimal surgical management, prognostic significance of sentinel node biopsy (SLNB), and benefits of interferon (IFN) for these patients are unclear. As a continuum of increasing tumor thickness is placed into a single TM group, differences in biologic and clinical behavior may be lost. The purpose of this study was to better characterize the diverse biology in TM, including the value of increasing thickness and nodal status information, potentially identifying high risk TM subgroups that may warrant more aggressive treatment/follow up.</p> <p>Methods</p> <p>155 consecutive TM patients treated at a single institution between 1971 and 2007 were retrospectively reviewed. Patient, disease and treatment features were analyzed with respect to disease-free (DFS) and overall survival (OS).</p> <p>Results</p> <p>Median patient age was 66 years and 68% of patients were men. The trunk was the most common TM location (35%), followed by the head and neck (29%) and lower extremities (20%). Median thickness was 6 mm and 61% were ulcerated. 6% patients had stage IV disease, 12% had clinical nodal metastases. Clinically negative lymph node basins were treated by observation (22 patients - 15.4%), elective lymph node dissection (ELND) (24 patients - 17.6%) or SLNB (91 patients - 67%). 75% of ELND's and 53% of SLNB's were positive. Completion node dissection was performed in 38 SLNB+ patients and 22% had additional positive nodes. 17% of the study patients received IFN. At median follow up of 26 months, 5 year DFS and OS were 42% and 43.6%. For SLNB positive vs negative, median DFS were 22 vs 111 months (p = 0.006) and median OS were 41 vs 111 months (p = 0.006). When stratified by tumor thickness ≤ vs > 6 mm, 5 year DFS was 58.3% vs 20% (p < 0.0001) and OS was 62% vs 20% (P < 0.0001). IFN had no impact on DFS or OS (p = 0.98 and 0.8 respectively).</p> <p>Conclusion</p> <p>Within the high risk group of patients with TM, cases with tumor thickness > 6 mm or a positive SLNB had a significantly worse DFS and OS (p < .0001, <.0001 and .006, .006).</p

Melanoma Patients with Positive Sentinel Nodes Who Did Not Undergo Completion Lymphadenectomy: A Multi-Institutional Study

Completion lymph node dissection (CLND) is considered the standard of care in melanoma patients found to have sentinel lymph node (SLN) metastasis. However, the therapeutic utility of CLND is not known. The natural history of patients with positive SLNs who do not undergo CLND is undefined. This multi-institutional study was undertaken to characterize patterns of failure and survival rates in these patients and to compare results with those of positive-SLN patients who underwent CLND.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45875/1/10434_2006_Article_10237.pd

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

Purpose To determine the survival rates and independent predictors of survival using a contemporary international cohort of patients with stage III melanoma. Patients and Methods Complete 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. Results Among 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 < .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 < .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 < .01). Conclusion In 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

Prognostic Significance of Mitotic Rate in Localized Primary Cutaneous Melanoma: An Analysis of Patients in the Multi-Institutional American Joint Committee on Cancer Melanoma Staging Database

Purpose The aim of this study was to assess the independent prognostic value of primary tumor mitotic rate compared with other clinical and pathologic features of stages I and II melanoma. Methods From the American Joint Committee on Cancer (AJCC) melanoma staging database, information was extracted for 13,296 patients with stages I and II disease who had mitotic rate data available. Results Survival times declined as mitotic rate increased. Ten-year survival ranged from 93% for patients whose tumors had 0 mitosis/mm(2) to 48% for those with >= 20/mm(2) (P 8 mm). Ulceration was also associated with a higher mitotic rate; 59% of ulcerated melanomas had >= 5 mitoses/mm(2) compared with 16% of nonulcerated melanomas (P < .001). In a multivariate analysis of 10,233 patients, the independent predictive factors for survival in order of statistical significance were as follows: tumor thickness (chi(2) = 104.9; P < .001), mitotic rate (chi(2) = 67.0; P < .001), patient age (chi(2) = 48.2; P < .001), ulceration (chi(2) = 46.4; P < .001), anatomic site (chi(2) = 34.6; P < .001), and patient sex (chi(2) = 33.9; P < .001). Clark level of invasion was not an independent predictor of survival (chi(2) = 3.2; P = .37). Conclusion A high mitotic rate in a primary melanoma is associated with a lower survival probability. Among the independent predictors of melanoma-specific survival, mitotic rate was the strongest prognostic factor after tumor thickness. J Clin Oncol 29: 2199-2205. (C) 2011 by American Society of Clinical Oncolog