European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma: Part 2. Treatment - update 2026

Part 2 of the guideline addresses the updates on treatment recommendations in immunocompetent as well as immunosuppressed patients with invasive cutaneous squamous cell carcinoma (CSCC), based on current literature and expert consensus. A multidisciplinary panel of experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), the European Society for Radiotherapy and Oncology (ESTRO), the European Union of Medical Specialists (UEMS)-Dermatology Venereology and the European Organization of Research and Treatment of Cancer (EORTC), was formed to update the previous guideline on CSCC (version 2023). For common primary CSCC, first-line treatment is surgical excision with post-operative margin assessment or micrographically controlled surgery. Achieving clear histological margins is key for patients with CSCC amenable to surgery. Radiotherapy should be considered for non-surgical candidates/tumors. For patients with macroscopic regional lymph node metastases, individualized treatment should be discussed in the multidisciplinary tumor board. For patients with metastatic or locally advanced CSCC who are not candidates for curative surgery or radiotherapy, anti-PD-1 agents are the first-line systemic treatment, with cemiplimab being the approved systemic agent for advanced CSCC by the EMA. Second-line systemic treatments for advanced CSCC, include clinical trials, EGFR inhibitors (cetuximab) combined with anti-PD-1 immunotherapy, or chemotherapy or radiotherapy. The decision for adjuvant cemiplimab for CSCC at high risk of recurrence after surgery and radiotherapy should be discussed in the multidisciplinary tumor board. In addition, multidisciplinary board decisions are mandatory for all patients with advanced CSCC, considering the risks of toxicity, the age and frailty of patients and co-morbidities, including immunosuppression. Patients should be engaged in informed, shared decision-making on management and be provided with best supportive care to improve symptom management and quality of life. Frequency of follow-up visits and investigations for subsequent new CSCC depend on underlying risk characteristics.