Educational Review: Neoadjuvant Approaches to Melanoma

Background With the development of novel systemic therapies, the treatment of patients with melanoma has changed drastically over the past few years, especially with regard to neoadjuvant treatments. Standard of care for patients with resectable stage III/IV melanoma traditionally consisted of surgery, with possible adjuvant treatment. However, there have been promising improvements in patient outcomes with neoadjuvant treatment compared to upfront surgery, specifically with targeted and immune therapies. Methods A review of clinical trials in the neoadjuvant treatment of stage III/IV melanoma was performed. Results Multiple phase I-II clinical trials have investigated the utility of interferon, targeted therapies (i.e., BRAF and/or MEK inhibitors) and immune checkpoint inhibitors (i.e., PD-1 or CTLA-4 inhibitors) in the treatment of resectable clinical stage III/IV melanoma. Large strides have been made with regards to optimal treatment strategy and dosing, to maximize clinical and pathologic response rates while minimizing toxicities. Additionally, complete pathologic response to neoadjuvant therapies translates to a disease-free survival benefit. Current and future directions include individualizing surgical and adjuvant therapy based on patient response to neoadjuvant treatments. Conclusions The current evidence, represented by small phase I-II trials, demonstrates advantages to neoadjuvant treatment with targeted or immune therapy for patients with resectable stage III/IV melanoma. Future research is needed to determine the advantages of neoadjuvant compared to adjuvant treatment, and to further refine treatment strategies based on patient response.