Neoadjuvant therapy in skin cancer: current evidence and future perspectives

The development of immune checkpoint inhibitors and targeted therapies has fundamentally changed the treatment of cutaneous malignancies, especially in squamous cell carcinoma, melanoma, and Merkel cell carcinoma. The latest neoadjuvant approaches have shown promising results in locally advanced stages. In squamous cell carcinoma, neoadjuvant PD-1 blockade with cemiplimab has demonstrated a high pathological response rate. Initial data additionally indicate a lowered risk of recurrence. Even greater progress has been made in melanoma: Neoadjuvant PD-1 blockade, both alone and in combination with a CTLA-4 blocker, significantly reduces the risk of recurrence. Both the randomized Phase II SWOG1801 study and the randomized Phase III NADINA study have demonstrated the superiority of the neoadjuvant approach over a pure adjuvant one. The results of the NADINA study showed that a deep pathological response to neoadjuvant therapy allows treatment de-escalation by omission of adjuvant therapy. Targeted therapies with BRAF-MEK inhibition also show adequate response rates in BRAF-mutated melanomas. In Merkel cell carcinoma, the neoadjuvant administration of PD-1 inhibitors like Nivolumab shows a high response rate and promising survival data. In summary, the data highlight the potential of neoadjuvant therapy in the treatment of locally advanced skin tumors, reducing the risk of recurrence and mortality, as well as providing new opportunities for therapy de-escalation.