Who Should Be Offered a Sentinel Node Biopsy for Melanoma Less Than 1 mm in Thickness? (2013)

Melanoma has become a significant health problem during the last few decades, with more than 76,000 cases expected in the United States in 2013. As the incidence of melanoma began to increase, new techniques were developed to stage and treat these patients. Sentinel lymph node biopsy, also known as selective lymphadenectomy, was first described by Morton et al in 1992 as a way to accurately stage the regional nodal basin in patients with cutaneous melanoma and clinically negative lymph nodes. Although some controversy remains as to the benefit of performing a sentinel node biopsy in patients with cutaneous melanoma, the utility of this technique as a staging modality is generally accepted. Multiple studies have shown that the status of the sentinel lymph node is one of the most important prognostic factors in patients with cutaneous melanoma, and sentinel node status has been incorporated into the most recent updates to the American Joint Committee on Cancer (AJCC) melanoma staging system. It is also generally accepted that in patients with primary melanomas between 1 mm and 4 mm in Breslow thickness, the risk of occult nodal metastases is great enough to warrant a sentinel node biopsy. However, controversy remains as to when to perform sentinel lymph node biopsy in patients with melanomas less than 1 mm in thickness, although the prognostic significance of a positive sentinel node in these patients has been established, with a worse 5-year melanoma-specific survival in patients with occult nodal disease. In an attempt to identify patients with melanomas less than 1 mm in thickness who may benefit from a sentinel node biopsy, recent studies have focused on other characteristics of the patient and the primary melanoma as possible significant prognostic variables. These include patient age, sex, the presence of ulceration, mitotic index, Clark level, the presence of regression or lymphovascular invasion, and location on the body of the primary. The authors of these studies have drawn different conclusions, and a definitive set of criteria to guide clinicians has remained elusive. The study reported in the article by Han et al that accompanies this editorial attempts to better define criteria that clinicians can use to select patients with melanomas less than 1 mm in thickness who have a significant risk of harboring occult nodal metastatic disease. The authors are members of the Sentinel Lymph Node Working Group, an organization that consists of 30 member institutions. Patient data are submitted and updated by each member institution through a password-protected Web site into a standardized database that is maintained at Vanderbilt University in Nashville, TN. The authors used this database to examine patient records from 1994 to 2012 and identified 1,250 patients with melanomas less than 1 mm in thickness who had undergone sentinel lymph node biopsy. Their goal was to determine which clinicopathologic characteristics of the patients and their primary tumors would best predict the presence of occult disease in the sentinel lymph nodes. They included a range of covariates in their analysis, including age, sex, histologic type of melanoma, location of the primary, Breslow thickness, Clark level, the presence or absence of ulceration, mitotic rate, the presence or absence of regression, vertical versus radial growth phase, the presence or absence of lymphovascular invasion, and the degree of tumor infiltration by lymphocytes. Of the 1,250 patients in their data set, the authors found that 65 (5.2%) had positive sentinel lymph nodes. The only firm recommendation that the authors could draw from their analysis was that sentinel node biopsy should be performed for melanomas that are 0.75 mm or greater in thickness, but not for melanomas less than 0.75 mm in thickness. Their rationale for this recommendation was that 6.3% of patients in their study with melanomas that were 0.75 mm or greater in thickness had positive sentinel nodes, whereas patients with melanomas less than 0.75 mm in thickness had less than a 5% chance of having a positive sentinel node. This held true even when other factors, such as presence of ulceration or a Clark level of IV were taken into account; these factors increased the likelihood of finding a positive sentinel node only when the primary was at least 0.75 mm in thickness. Of patients with ulcerated primary tumors at least 0.75 mm in thickness, 14.7% had positive sentinel nodes, compared with only 6% of patients with nonulcerated tumors at least 0.75 mm in thickness. This is the main take-away lesson for clinicians: sentinel node biopsy can be avoided in patients with melanomas less than 0.75 mm in thickness and is recommended when the primary tumor is 0.75 mm or greater in thickness, especially if the primary is also ulcerated. Other variables that have been found to hold prognostic significance in previous studies, such as patient age, sex, presence of tumor infiltrating lymphocytes, and regression of the primary, were not found to predict the presence of occult nodal disease in the study by Han et al. Because this was a retrospective analysis using data from many different centers that use a variety of different techniques and methods for determining the characteristics of primary melanomas, the authors admit that it may be difficult to compare factors such as the presence or absence of regression, when subjective analysis is JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 31 NUMBER 35 DECEMBER 1