Abstract
Introduction of immunotherapy (IT) has radically changed the therapeutic scenario in patients affected by locally advanced and/or metastatic cutaneous squamous cell carcinoma (cSCC) patients. If it is well consolidated the role of immunotherapy in the setting of a disease not amenable to curative surgery and/or radiation, how to integrate immune checkpoint inhibitors in the curative setting is still under evaluation. Surgery combined or not with adjuvant radiotherapy remains the mainstay of curative treatment in localized cSCC; however, promising data with neoadjuvant or perioperative immunotherapy could pave the way towards treatment de-escalation according to the response achieved. On the other side, data on adjuvant treatment with pembrolizumab and cemiplimab after surgery and radiation are still awaited. Several questions related to the activity and the safety of immunotherapy in the real-world setting still remain without answer, and several points need to be better explored. In the current review we will explore the updated literature on the use of immunotherapy in cSCC, and we will show the current challenges in its use.