Multidisciplinary treatment strategies in high-risk resectable melanoma: Role of adjuvant and neoadjuvant therapy

•Adjuvant/neoadjuvant targeted and immunotherapies have shown benefit in melanoma.•Consensus in trial designs and clinical endpoints will aid future development.•Predictive biomarkers may enhance patient benefit and avoid undue toxicity. Stage III melanoma encompasses a range of disease burdens, including microscopic foci of metastatic melanoma in a sentinel lymph node; bulky, clinically detected lymphadenopathy; and in-transit dermal metastases. After initial surgical management, patients with stage III melanoma at highest risk for recurrence are most likely to benefit from adjuvant therapy. Novel therapies that have improved the disease response rates and long-term survival of patients with advanced or metastatic melanoma have now been evaluated in the adjuvant setting, with the goal of eliminating residual microscopic disease to improve relapse-free and overall survival. Alternatively, implementing systemic therapies in the neoadjuvant setting for bulky, clinically detected disease can potentially limit surgical morbidity and improve understanding of an individual’s response to applied therapy. With multiple therapeutic approaches currently under evaluation for adjuvant and neoadjuvant treatment of high-risk melanoma, establishing optimal treatment regimens, appropriate clinical endpoints, and treatment risk-benefit profiles has become increasingly challenging. There is also a critical need to identify and validate biomarkers predictive of melanoma patient outcomes or treatment efficacy. This article provides an overview of current clinical evidence and ongoing trials of targeted therapy and immunotherapy in this rapidly evolving area of oncology.