Randomized adjuvant therapy trials in melanoma: surgical and systemic.

The utility of adjuvant surgical procedures in the management of primary melanomas has been evaluated in a large number of phase III randomized trials. These trials have shown that wide margins, elective lymph node dissection, sentinel lymph node (SLN) biopsy, and prophylactic isolated limb perfusion (ILP) do not improve survival but may improve locoregional control. Based on the claim of providing a survival benefit, these surgical procedures cannot be considered standard of care in the routine management of primary melanoma. Regarding the role of SLN biopsy it must be stated that this procedure provides the best information on prognosis and provides us with an important tool to stratify for and study more homogeneous patient populations to evaluate adjuvant systemic therapies in randomized phase III trials. The utility of systemic adjuvant therapy remains marginal as a result of the fact that a lack of effective drugs in stage IV disease is reflected by a lack of effective adjuvant therapies in stage II-III melanoma. Thus far, chemotherapeutic drugs, immunostimulants, and various vaccines have all failed. Interferon (IFN) has an effect on relapse-free survival but not on overall survival. Thus its impact is judged by many to be too small to be considered standard of care. The population of patients that can benefit from IFN needs to be better defined by identifying new biomarkers by genomic and proteomic studies, which are ongoing.