Adjuvant therapy of malignant melanoma and the role of sentinel node mapping

Controversy still exists about standard management of a primary melanoma. Over the last decades randomized phase III trials have addressed questions about the width of margin in relation to the Breslow thickness of the primary lesion, the role of prophylactic isolated limb perfusion, and the role of elective lymph node dissection. Overall these trials have demonstrated that less extensive surgery is as good as more extensive surgery. Wide excision margins, prophylactic isolated limb perfusions, or the elective lymph node dissection did not improve overall survival significantly in any of the phase III trials conducted.

No standard systemic adjuvant therapy with confirmed impact on overall survival has been identified thus far for clinically node negative stage I-II (TxN0M0) patients after excision of the primary, nor for clinically node positive stage III (TxN1-2M0) patients after lymph node dissection for metastatic regional node involvement. Poor Staging in the Past. One of the main problems associated with the trials assessing systemic adjuvant treatments in management of high risk primary melanoma is the fact that in general patients were poorly staged. About 25%-30% of patients with primaries thicker than 1.5 mm have micro-metastatic disease in the regional lymph nodes and beyond. This population was usually submerged by the other 70%-75% of the patients with excellent prognosis, obscuring the potential benefit of the adjuvant surgical procedure (ELND) or a systemic adjuvant treatment.

Sentinel lymph node (SLN) mapping is resolving many of the inadequacies of the past and has completely changed the management of primary melanoma. As a small procedure with low morbidity it identifies that part of the population which has microscopic involvement of regional lymph nodes with greater precision than an elective lymph node dissection. SLN-mapping allows for a detailed histopathologic evaluation involving multiple sections, H&E staining in combination with IHC (immunohistochemical staining) of the node with the highest chance of containing metastatic foci. Moreover in the near future it is most likely that RT-PCR on negative nodes will complete the diagnostic workup as a promising last step in the procedure to determine whether tumor cells are present in the sentinel node. Sentinel lymph node status has been shown recently to be by far the strongest independent prognostic factor of melanoma stage I-II patients. SLN-status is a much stronger prognostic factor than tumor thickness, which looses its prognostic relevance in SLN-positive patients.

Thus we now have a procedure by which the melanoma stage I-II population can be dissected in a group at truly high risk for recurrence and a group with truly low risk of recurrence. The high risk group with a greater than 75% chance for systemic disease can then be selected for trial participation of various systemic adjuvant therapy regimens that may be allowed to be toxic, considering the very high risk for relapse in these patients. The node negative group of patients can be selected for participation in trials evaluating systemic adjuvant treatment of low toxicity considering the low chance for distant metastatic disease.