Abstract

Simple SummaryCutaneous squamous cell carcinoma (cSCC) is an increasingly prevalent and morbid cancer worldwide. Management of this cancer has changed significantly in the last decade through improved risk stratification and new therapies offering patients with locally advanced and metastatic disease more effective, less toxic, and more durable treatment options. Ongoing clinical trials are assessing new therapeutic options as well as optimizing existing regimens in efforts to better manage this cancer. The recent developments highlight the need for multidisciplinary care, especially for those with locally advanced and metastatic disease.cSCC is increasing in prevalence due to increased lifespans and improvements in survival for conditions that increase the risk of cSCC. The absolute mortality of cSCC exceeds melanoma in the United States and approaches that of melanoma worldwide. This review presents significant changes in the management of cSCC, focusing on improvements in risk stratification, new treatment options, optimization of existing treatments, and prevention strategies. One major breakthrough in cSCC treatment is the advent of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1), which have ushered in a renaissance in the treatment of patients with locally advanced and metastatic disease. These agents have offered patients with advanced disease decreased therapeutic toxicity compared to traditional chemotherapy agents, a more durable response after discontinuation, and improved survival. cSCC is an active field of research, and this review will highlight some of the novel and more developed clinical trials that are likely to impact cSCC management in the near future.

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