Cutaneous squamous cell carcinoma (CSCC) is becoming increasingly defined by personalized treatment decisions based on whether tumors are surgically removable. Unlike basal cell carcinoma, which grows slowly and rarely spreads, CSCC is more aggressive and can invade nerves, lymph nodes, and distant organs, especially in immunosuppressed patients. For unresectable or metastatic disease, FDA-approved anti–PD-1 immunotherapies now serve as standard first-line treatment, producing durable responses in many patients. In borderline resectable cases, immunotherapy is increasingly used before surgery to shrink tumors and preserve critical structures such as the eyes or facial nerves.
Treatment strategies continued evolving in 2025 and 2026. Cemiplimab gained FDA approval in October 2025 as adjuvant therapy for high-risk CSCC following surgery and radiation after the phase 3 C-POST trial showed a 68% reduction in recurrence or death risk. Researchers are also studying neoadjuvant immunotherapy before surgery in the ongoing phase 3 NRG-HN014 trial. Although anti–PD-1 therapies are generally well tolerated, experts caution that delayed and potentially severe immune-related side effects require close monitoring.