Controversy exists as to which patients may benefit from inguinal-femoral lymphadenectomy. A prospective study by the GOG demonstrated that the risk of inguinal-femoral lymph node metastasis correlated with the Breslow microstage (165). As with cutaneous melanoma, it appears that for superficial lesions (Breslow tumor thickness <0.76 mm), the risk for nodal spread is so low that routine lymphadenectomy is not indicated as long as the nodes appear clinically free of disease. For intermediate-thickness (1 to 4 mm) cutaneous melanoma, a randomized controlled trial of elective lymph node dissection versus observation showed a 5-year survival advantage for patients who underwent elective lymph node dissection, who were younger than 60 years, and whose tumors were characterized by 1-to 2-mm thickness and no ulcerations (178). Patients with deeply invasive cutaneous melanomas (>4-mm tumor thickness) have a high risk of regional and systemic metastases and are unlikely to benefit from regional lymphadenectomy (179). Given some of the epidemiologic, histologic, and prognostic differences between vulvar and cutaneous melanoma, extrapolation of these data to the vulva should be done with caution (180). Specific to patients with vulvar melanoma, there is a small body of literature to suggest that there may be a clinical benefit in elective groin lymphadenectomy and the resection of clinically positive nodes (162,163). The role of the sentinel lymph node procedure in vulvar melanoma is under investigation. In cutaneous melanoma, sentinel lymph node biopsy replaced elective lymph node dissection in patients with clinically negative nodes, as it provides the same prognostic information with reduced morbidity. Only patients with metastatic disease undergo completion lymphadenectomy. Results from an interim analysis of the Multicenter Selective Lymphadenectomy Trial confirmed the prognostic value of the sentinel node procedure. These data suggest that an immediate completion lymphadenectomy following detection of a positive sentinel lymph node improves survival in patients with regional nodal metastases (181). Studies on the sentinel lymph node procedure for vulvar melanoma are limited. A review of the literature estimates a false-negative rate of about 15% (182). Although the sentinel node procedure appears appropriate for select patients with vulvar melanoma, the importance of an expert team familiar with the procedure and consisting of a gynecologic oncologist, a nuclear medicine specialist, and a pathologist with expertise in microstaging cannot be overemphasized.
Pelvic node metastases do not occur in the absence of groin node metastases (177,183,184). The prognosis for patients with positive pelvic nodes is so poor that there seems to be no value in performing pelvic lymphadenectomy for this disease. Immunotherapy and chemotherapy have demonstrated modest results in cutaneous melanoma. Several randomized cooperative and Intergroup trials of high-risk melanoma patients demonstrated a small but significant improvement in disease-free and overall survival with adjuvant interferon alpha (185–187). Dacarbazine (DTIC) is considered the most active single-agent chemotherapy, with a response rate of 16%, and randomized controlled trials failed to demonstrate superiority of any multiagent regimen (188). Targeted therapy is an area of promising development as single agents, in combination, and combined with chemotherapy. A vaccine stimulating both antibody and T-cell responses against melanoma is a promising but experimental treatment that is under investigation (189). Estrogen receptors were demonstrated in human melanomas, and an occasional response to tamoxifen was reported (190,191). Traditionally, melanomas were thought to be radiation resistant. There is a growing body of literature for advanced, high-risk, lymph node–metastatic cutaneous melanoma, demonstrating improved locoregional disease control compared to surgery with therapeutic lymphadenectomy alone (192,193).