Neoadjuvant Therapy: Changes in the Management of Macroscopic Stage III/Resectable Stage IV Melanoma

Existing adjuvant therapies improve outcomes for resected stage III and IV melanoma patients but fail in almost half to prevent recurrence and death. Large, multi-institution, randomized studies firmly establish the superiority of neoadjuvant to adjuvant therapy alone. Checkpoint inhibition, either anti-programmed cell death protein 1 monotherapy or combination with CTLA-4/LAG-3 blockage, demonstrates more durable event-free survival compared to targeted or targeted/immunotherapy combination therapies. Novel combinations of intralesional immunotherapies and other agents aim to increase clinical efficacy and limit toxicity of therapies. Pathologic response to treatment remains as the best prognostic surrogate for clinical outcomes for patients.