Long-term survival as a treatment benchmark in melanoma: latest results and clinical implications

Historically, stage III-IV melanoma patients have had few options to achieve long-term survival. For patients with stage III disease, surgery alone may be curative for approximately 50%. Adjuvant treatment with a slightly greater impact on relapse-free survival at the cost of substantial toxicity, and studies are ongoing to test the adjuvant benefit of other immunotherapies that appear more active and less toxic in advanced melanoma. Achieving long term survival for stage IV patients had been rare until recently and progress was painfully slow with traditional cytotoxic chemotherapy; review of multiple phase II studies showed universally poor results. Fortunately, since the approval by the US Food and Drug Administration of agents targeting the cytotoxic T lymphocyte antigen-4 (CTLA-4) receptor, as well as those targeting B-raf and mitogen-activated protein kinase kinase (MEK) in the mitogen-activated protein kinase (MAPK) pathway for patients whose melanoma is 'driven' by a BRAF mutation, long-term survival of stage IV melanoma is increasing substantially. Here we review the examples of studies documenting potentially curative approaches to melanoma and propose suggestions for the use of various treatments in achieving this important goal.