History of Melanoma

Until the mid-twentieth century, the clinical and pathological features of melanoma were not well documented, prognostic factors were poorly understood, and the evidence base for management strategies was sadly deficient. Aggressive treatment approaches for both the primary melanoma site and the regional lymph nodes had been established by the early 1900s, and continuing as the standard of care until the early 1980s. Several clinical trials failed to demonstrate a survival benefit for patients having a very wide excision of their primary melanoma, or those having elective lymph node dissection (ELND), although in two of the largest studies there was a trend in favor of ELND. In 1992, Morton et al. reported the technique of sentinel node biopsy (SNB). This identified node-positive patients most likely to benefit from a completion lymph node dissection (CLND). A large international trial, MSLT-I, showed no overall survival benefit for SNB, but did show a substantial survival benefit for SN-positive patients treated by immediate CLND compared to patients whose regional nodes were simply observed, and treated by CLND only if nodal metastases later became apparent. Initial results of a second trial initiated by Morton, MSLT-II, indicate that routine CLND in SN-positive patients confers no additional survival benefit. In the last decade, targeted inhibitors of the MAP kinase pathway and immune checkpoint inhibitors have produced remarkable improvements in the previously dismal survival outcome for patients with systemic melanoma metastases. Furthermore, the role of these agents as neoadjuvant and adjuvant therapies in high-risk patients is currently being assessed.