ABSTRACT
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, representing 20%–50% of all skin cancers. The vast majority of cSCCs can be cured with surgery alone, with 5-year cure rates exceeding 90%. A minority of cases have high-risk features with increased risk of regional and distant metastasis. The prognosis of these advanced cases is considerably lower. Various staging systems have attempted to identify patients who fall into this category, including the Brigham and Women’s Hospital and the AJCC staging systems (seventh and eighth editions). There may be a role for imaging and sentinel lymph node biopsy (SLNB) in certain high-risk cSCC cases to identify patients at the highest risk of metastatic disease. However, it is still unclear whether SLNB improves overall survival. Radiation therapy is an alternative treatment option for non-surgical candidates. Until recently, there has been a dearth of systemic therapies that provide a durable response for metastatic cSCCs. More recently, cemiplimab, a programmed cell death-1 inhibitor, was approved for use in advanced cSCC showing improved survival. The following cases demonstrate different approaches to the management of various stages of high-risk cSCC.
