In order to update recommendations on treatment, supportive care, education, and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), 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), the European Academy of Dermatology and Venereology (EADV), and the European Organisation of Research and Treatment of Cancer (EORTC) was formed. Recommendations were based on an evidence-based literature review, guidelines, and expert consensus. Treatment recommendations are presented for common primary cSCC (low risk, high risk), locally advanced cSCC, regional metastatic cSCC (operable or inoperable), and distant metastatic cSCC. For common primary cSCC, the first-line treatment is surgical excision with postoperative margin assessment or micrographically controlled surgery. Achieving clear surgical margins is the most important treatment consideration for patients with cSCCs amenable to surgery. Regarding adjuvant radiotherapy for patients with high-risk localised cSCC with clear surgical margins, current evidence has not shown significant benefit for those with at least one high-risk factor. Radiotherapy should be considered as the primary treatment for non-surgical candidates/tumours. For cSCC with cytologically or histologically confirmed regional nodal metastasis, lymph node dissection is recommended. 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 first approved systemic agent for advanced cSCC by the Food and Drugs Administration/European Medicines Agency. Second-line systemic treatments for advanced cSCC, include epidermal growth factor receptor inhibitors (cetuximab) combined with chemotherapy or radiotherapy. 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 the best supportive care to improve symptom management and quality of life. The frequency of follow-up visits and investigations for subsequent new cSCC depends on underlying risk characteristics.

1st Department of Dermatology Aristotle University Thessaloniki Greece

1st Department of Dermatology Venereology National and Kapodistrian University of Athens Andreas Sygros Hospital Athens Greece

Aix Marseille University APHM Hospital Marseille France

Carol Davila University of Medicine and Pharmacy Bucharest Department of Oncologic Dermatology Elias University Hospital Bucharest Bucharest Romania

Centre for Cell Biology and Cutaneous Research Blizard Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London London UK

Centre for Dermatooncology Department of Dermatology Eberhard Karls University Tuebingen Germany

Department of Dermatology Coimbra Hospital and University Centre Coimbra Portugal

Department of Dermatology Medical Faculty Military Medical Academy Belgrade Serbia

Department of Dermatology Medical University of Vienna Vienna Austria

Department of Dermatology Papageorgiou Hospital Aristotle University Department of Medicine Thessaloniki Greece

Department of Dermatology University Hospital Erasme Université Libre de Bruxelles Brussels Belgium

Department of Dermatology University Hospital Kiel Germany

Department of Dermatology University of Trieste Trieste Italy

Department of Dermatology Venereology and Allergology Frankfurt University Hospital Frankfurt Germany

Department of Dermatovenereology 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of General and Oncologic Dermatology Ambroise Paré hospital APHP and EA 4340 'Biomarkers in Cancerology and Hemato oncology' UVSQ Université Paris Saclay Boulogne Billancourt France

Department of Medical and Surgical Dermatology Service Hospital Universitario Virgen Macarena Sevilla Spain

Department of Melanoma and Surgical Oncology Royal Prince Alfred Hospital Sydney New South Wales Australia; Faculty of Medicine and Health University of Sydney Sydney New South Wales Australia; Melanoma Institute Australia Sydney New South Wales Australia

Department of Oncology Odense University Hospital Odense Denmark

Dermatology Department of Biotechnological and Applied Clinical Sciences University of L'Aquila L'Aquila Italy

Dermatology Department of Hospital Clinic of Barcelona University of Barcelona IDIBAPS CIBER de enfermedades raras Instituto Carlos 3 Barcelona Spain

Dermatology Unit University of Rome La Sapienza Rome Italy

Division of Cancer Sciences University of Manchester Manchester UK; Department of Medical Oncology Christie NHS Foundation Trust Manchester UK

GROW School for Oncology and Reproduction Maastricht University Maastricht the Netherlands; Department of Dermatology Maastricht University Medical Centre Maastricht University Maastricht the Netherlands

Mount Vernon Cancer Centre East and North NHS Trust Northwood UK

Nantes Université INSERM CNRS Immunology and New Concepts in ImmunoTherapy INCIT UMR 1302 EMR6001 Nantes France

Skin Cancer Centre at University Hospital Zurich Switzerland

Université Paris Cite Dermato Oncology AP HP Hôpital Saint Louis Cancer Institute APHP Nord Université Paris Cite INSERM U976 Paris France

University Medical Center Utrecht and Princess Máxima Center Utrecht the Netherlands; Comprehensive Cancer Center Munich Technical University Munich and Ludwig Maximilian University Munich Germany

UOC di Dermatologia Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche Fondazione Policlinico Universitario A Gemelli IRCCS Rome Italy; Dermatologia Università Cattolica del Sacro Cuore Rome Italy

UOC Radioterapia Oncologica Dipartimento di Diagnostica per Immagini Radioterapia Oncologica ed Ematologia Fondazione Policlinico Universitario A Gemelli IRCCS Rome Italy

Citace poskytuje Crossref.org