Neoadjuvant systemic immunotherapy for skin cancers

Abstract Neoadjuvant treatment for skin cancer refers to treatment given to resectable tumors before surgery with the primary aim of improving prognostic outcomes. In addition, it may downstage the tumor to decrease surgical morbidity, and may de‐escalate adjuvant therapies in cases of complete response. This in‐depth review discusses the principles of neoadjuvant immunotherapy for cutaneous melanoma and invasive cutaneous squamous cell carcinoma (CSCC). Lessons learned from prospective neoadjuvant systemic immunotherapy clinical trials in melanoma are explored, available evidence from research studies for resectable CSCC is detailed, and key studies are illustrated in schematic figures. Outcomes and limitations of current evidence are presented and practical considerations are highlighted, including the risks of immune‐related adverse events and the need for biomarkers to identify patients most likely to benefit. Implications are illustrated for response‐adapted treatment de‐escalation protocols, and trials are indicated that could inform future standards of care. While clinical trials on neoadjuvant immunotherapy and dual checkpoint blockade strategies for melanoma is a rapidly growing field, the small number of clinical trials in CSCC highlights the need to design and perform clinical trials for patients with CSCC in order to be able to provide for them treatments based on high standards of research.