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Publications

Journal Article Review Ahead of print

PubMed: 42263355 DOI: 10.1016/j.ejca.2026.116764

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

Eur J Cancer 243:116764

Authors: Alexander J Stratigos, Clio Dessinioti, Claus Garbe, Celeste Lebbe, Teresa Amaral, Veronique Bataille, Brigitte Dreno, Reinhard Dummer, Maria Concetta Fargnoli, Ana Maria Forsea, Christoffer Gebhardt, Catherine A Harwood, Axel Hauschild, Christoph Hoeller, Lidija Kandolf-Sekulovic, Roland Kaufmann, Nicole Wj Kelleners-Smeets, Peter Koelblinger, Aimilios Lallas, Ulrike Leiter, Konstantinos Liopyris, Veronique Del Marmol, David Moreno-Ramirez, Giovanni Pellacani, Ketty Peris, Philippe Saiag, Luca Tagliaferri, Myrto Trakatelli, Ricardo Vieira, Iris Zalaudek, Petr Arenberger, Alexander C J van Akkooi, Alexander M M Eggermont, Paul Lorigan, Mario Mandala, Josep Malvehy

Affiliations

  • 1st Department of Dermatology-Venereology, Andreas Sygros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
  • 1st Department of Dermatology-Venereology, Andreas Sygros Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
  • Centre for Dermatooncology, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany.
  • Université Paris Cite,AP-HP Dermato-oncology and CIC, Cancer institute APHP.nord Paris cité, INSERM U1342 - Equipe 1 - CNRS EMR8000, Saint Louis Hospital, Paris, France.
  • Institute Strauss, 3 Rue de la Prte de l'Hôpital, Strasbourg 67000, France.
  • 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, F-44000 Nantes, France.
  • Skin cancer Centre at University Hospital Zurich and University Zurich, Zurich, Switzerland; Kantonsspital Aarau, Switzerland.
  • San Gallicano Dermatological Institute, IRCCS, Rome, Italy.
  • Carol Davila University of Medicine and Pharmacy Bucharest, Department of Oncologic Dermatology, Elias University Hospital Bucharest, Romania; Health and Medical University Potsdam, Potsdam, Germany.
  • Department of Dermatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK.
  • Department of Dermatology, University Hospital (UKSH), Kiel, Germany.
  • Department of Dermatology, Medical University of Vienna, Austria.
  • Department of Dermatology, Medical Faculty, Military Medical Academy, Belgrade, Serbia.
  • Department of Dermatology, Mainz University Medicine, Mainz, Germany.
  • Department of Dermatology, Maastricht University Medical Centre+, GROW-School for Oncology and Reproduction, Maastricht University, Maastricht, Netherlands.
  • Department of Dermatology and Venerology, Paracelsus Medical University, Salzburg, Austria.
  • First Department of Dermatology, School of Medicine, Faculty of Health Sciences, Aristotle University, Thessaloniki, Greece.
  • Department of Dermatology, University Hospital Erasme, Université Libre de Bruxelles, Belgium.
  • Department of Medical-&-Surgical Dermatology Service. Hospital Universitario Virgen Macarena, Sevilla, Spain.
  • Dermatology Unit, University of Rome La Sapienza, Rome, Italy.
  • 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.
  • Department of General and Oncologic Dermatology, Ambroise-Paré hospital, APHP, & EA 4340 "Biomarkers in cancerology and hemato-oncology", UVSQ, Université Paris-Saclay, Boulogne-Billancourt, France.
  • Dipartimento di Diagnostica per Immagini e Radioterapia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy.
  • Department of Dermatology, Papageorgiou Hospital, Aristotle University Department of Medicine, Thessaloniki, Greece.
  • Coimbra Hospital and University Centre, Coimbra, Portugal.
  • Department of Dermatology, University of Trieste, Italy.
  • Department of Dermatovenereology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
  • Department of Melanoma and Surgical Oncology, Institute of Academic Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Faculty of Medicine & Health, University of Sydney, Sydney, New South Wales, Australia; Melanoma Institute Australia, Sydney, New South Wales, Australia.
  • University Medical Center Utrecht & Princess Máxima Center, Utrecht 3584 CS, the Netherlands; Comprehensive Cancer Center Munich, Technical University Munich & Ludwig Maximilian University, Munich, Germany.
  • Department of Medical Oncology, Christie NHS Foundation Trust, Division of Cancer Sciences, University of Manchester, United Kingdom.
  • University of Perugia, Perugia, Italy.
  • Dermatology Department of Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, CIBER de enfermedades raras, Instituto Carlos III, Spain.

Abstract

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.

MeSH

Radiotherapy, Cells, Carcinoma, Squamous Cell, Neoplasms, Therapeutics, Cutaneous Squamous Cell Carcinoma