Introduction: In recent years, the introduction of targeted therapy and immunotherapy into clinical practice has radically changed the management of advanced melanoma. More recently, these treatments also became the standard of care in the adjuvant setting. However, high-risk resectable stage III melanoma (i.e. with clinically detected regional lymph node involvement and/or satellites/in transit metastases) still has a high risk of relapse, even after adjuvant treatment, suggesting that the activity of immunotherapy and targeted therapy may play a relevant role in a neoadjuvant setting.Area covered: In this review, we discuss the results of the main clinical trials conducted in the neoadjuvant setting for patients with resectable stage III and stage IV melanoma, with a focus on the hot topics and a look at the future perspectives of the field.Expert opinion: The long-term effects of immunotherapy and the high response rate of targeted therapy provided the strong rationale to start neoadjuvant clinical trials for patients with resectable stage III and oligometastatic stage IV melanoma. Neoadjuvant therapy may play an important role not only for its possible impact on overall survival, but also as a predictive biological marker to allow for a more accurate personalization of adjuvant treatments.
Keywords: Melanoma; immunotherapy; neoadjuvant; oligometastatic stage IV; stage III; targeted therapy.