The Landmark Series: Neoadjuvant Systemic Therapy (NAST) for Stage 3 Melanoma Patients – A Potential Paradigm Shift in Management

Since the advent of effective systemic therapy, quantum changes have occurred in the multidisciplinary management strategies used for patients with American Joint Committee on Cancer stages 3 and 4 melanoma. For high-risk stage 3 patients, neoadjuvant immune checkpoint blockade (ICB) and targeted therapies present a promising novel approach to improving survival outcomes. In particular, patients who respond to ICB have an excellent prognosis, and clinical trials are ongoing to investigate whether those with a pathologic complete response (pCR) or near-pCR in a single node may avoid therapeutic lymph node dissection and adjuvant therapy. Toxicities currently are acceptably low, but when toxic events occur, they can have an enduring impact on a patient’s quality of life. To date, nearly all patients evaluated after treatment with neoadjuvant dabrafenib plus trametinib have some clinical and pathologic response. Patients who achieve pCR have improved prognosis, but pCR is not as reliable a predictor of improved outcome as pCR or near-pCR after neoadjuvant ICB. Ongoing studies should ideally be coordinated through the International Neoadjuvant Melanoma Consortium to ensure maximal efficiency at improving outcomes for melanoma patients.