Standards and Trends in the Treatment of Malignant Melanoma

Malignant melanoma is the most important and most aggressive tumor in dermatology. The primary tumor is removed in toto observing evidence-based safety margins. Elective lymph node dissection is not a therapeutic standard as prospective clinical trials did not reach a benefit in prognosis. By contrast, the sentinel node biopsy is a standard procedure – indicated at a tumor thickness above 1 mm and allowing an early detection of metastazing tumor cells. Detection of locoregional micrometastases by sentinel node biopsy and a subsequent dissection significantly prolong relapse-free survival, but not overall survival. The stage I/II-approved adjuvant therapy with interferon-α in low dose merely prolongs relapse-free survival. At stage III, when lymph node metastases appear, complete lymph node dissection is performed under standardized conditions. Adjuvant therapy consists of administration of interferon-α following an approved high-dose protocol. At stage IV, it is of importance to examine operability as complete surgical removal of the tumor extends mean survival significantly. In most of the cases, however, tumor-free (R0) situations are not achieved. In this case, systemic therapies are considered. So far, significant prolongation of survival could not be reached by any treatment modality, whether monochemotherapy, monochemotherapy in combination with interferon-α or interleukin-2 (biochemotherapy), polychemotherapy or polychemobiotherapy. Only temporary remission is achieved with the monochemotherapy whereas remission is more frequent with polychemobiotherapy. However, higher response rates are associated with increased toxicity. Polychemotherapy and polychemobiotherapy should only be used if symptomatic metastases occur. Improvement of therapeutic options of malignant melanoma are based on vaccination strategies, on an immune modulation, such as the inhibition of counter-regulatory mechanisms in T cells, and on kinase inhibitors, which all represent the entry into a targeted, individualized therapy in melanoma.