Cutaneous squamous cell carcinoma: Risk factors and new systemic treatment options in advanced disease

Abstract

Cutaneous squamous cell carcinoma (cSCC) accounts for approximately 20% of all skin cancers. Its rising incidence represents a major public health concern. The majority of cSCC are curable by surgical resection. Although less than 5% of cSCC patients develop metastases or local recurrence after complete excision, advanced cSCC is difficult to treat. Until recently, no standard therapeutic regimen for advanced cSCC exists. Traditional therapies include chemotherapy and EGFR-targeted therapy, but their clinical benefit remains modest and has been demonstrated mostly in retrospective studies. On the contrary, PD-1 inhibitors dramatically improve outcomes in many immunocompetent cSCC patients, resulting in the approval of cemiplimab as the first FDA-approved systemic drug for patients with locally advanced or metastatic cSCC who are not candidates for curative surgery or radiation. In the coming years combination therapies are an emerging treatment strategy that could improve efficacy of PD-1 inhibitors in advanced cSCC. Moreover, several prospective controlled trials have been designed to explore the potential role of PD-1 inhibitors in the adjuvant and neodjuvant setting. Given the paucity of data, the management of immunocompromised cSCC patients requires a heightened awareness in this new era of cancer therapeutics.