Immunotherapy for Nonmelanoma Skin Cancer: Facts and Hopes

Abstract Nonmelanoma skin cancer (NMSC) is the most frequently diagnosed malignancy in humans, representing a broad range of cutaneous tumors. Keratinocyte carcinomas, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC), are the most common NMSCs. The incidence of BCC and CSCC is steadily increasing due to a progressively aging population, chronic exposure to ultraviolet radiation, and increased awareness with earlier diagnosis. Rarer NMSCs, such as Merkel cell carcinoma (MCC) and cutaneous adnexal carcinomas, are also on the rise. Although the majority of NMSC tumors are localized at diagnosis and managed effectively with curative surgery and radiation, in rare cases with nodal and distant metastases, systemic therapy is often required. As our understanding of the immunologic characteristics of NMSCs has improved, effective treatment options have expanded with the development of immunotherapy. The FDA recently approved several immune checkpoint inhibitors for the treatment of locally advanced and metastatic MCC, CSCC, and BCC. We review the emerging role of immunotherapy as the standard of care for several advanced NMSCs not amenable to surgery and/or radiation and underscore the need for considering clinical trials of novel strategies in patients when immunotherapy does not provide durable benefit. Finally, we explore the potential of neoadjuvant and adjuvant immunotherapy.