Optimal systemic therapy for high-risk resectable melanoma

Immunotherapy with immune-checkpoint inhibitors and molecularly targeted therapy with BRAF inhibitors were pioneered in the setting of advanced-stage, unresectable melanoma, where they revolutionized treatment and considerably improved patient survival. These therapeutic approaches have also been successfully transitioned into the resectable disease setting, with the regulatory approvals of ipilimumab, pembrolizumab, nivolumab, and dabrafenib plus trametinib as postoperative (adjuvant) treatments for various, overlapping groups of patients with high-risk melanoma. Moreover, these agents have shown variable promise when used in the preoperative (neoadjuvant) period. The expanding range of treatment options available for resectable high-risk melanoma, all of which come with risks as well as benefits, raises questions over selection of the optimal therapeutic strategy and agents for each individual, also considering that many patients might be cured with surgery alone. Furthermore, the use of perioperative therapy has potentially important implications for the management of patients who have disease recurrence. In this Viewpoint, we asked four expert investigators and medical or surgical oncologists who have been involved in the key studies of perioperative systemic therapies for their perspectives on the optimal management of patients with high-risk melanoma.