A unique collaboration of multi-disciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with one to two-centimeter safety margins. For a correct stage classification and treatment decision, a sentinel lymph node biopsy shall be offered in patients with tumor thickness ≥ 1.0 mm or ≥ 0.8 mm with additional histological risk factors, although there is as yet no clear survival benefit for this approach. Therapeutic decisions should be primarily made by an interdisciplinary oncology team ("Tumor Board"). Adjuvant therapies can be proposed in completely resected stage IIB-IV. In stage II only PD-1 inhibitors are approved. In stage III anti-PD-1 therapy or dabrafenib plus trametinib for patients with BRAFV600 mutated melanoma can be discussed. In resected stage IV, nivolumab can be offered, as well as ipilimumab and nivolumab, in selected, high-risk patients. In patients with clinically detected macroscopic, resectable disease, neoadjuvant therapy with ipilimumab plus nivolumab followed complete surgical resection and adjuvant therapy according to pathological response and BRAF status can be offered. Neoadjuvant therapy with pembrolizumab followed by complete surgical resection and adjuvant pembrolizumab is also recommended. For patients with disease recurrence after (neo) adjuvant therapy, further treatment should consider the type of (neo) adjuvant therapy received as well as the time of recurrence, i.e., on or off therapy. In patients with irresectable stage III/IV disease systemic treatment is always indicated. For first line treatment PD-1 antibodies alone or in combination with CTLA-4 or LAG-3 antibodies shall be considered. In stage IV melanoma with a BRAFV600 mutation, first-line therapy with BRAF/MEK inhibitors can be offered as an alternative to immunotherapy, in selected cases. In patients with primary resistance to immunotherapy and harboring a BRAFV600 mutation, this therapy shall be offered as second line. Other second line therapies include therapy with tumor infiltrating lymphocytes and combinations of immune checkpoint inhibitors not used in first line. This guideline is valid until the end of 2026.

1st Department of Dermatology Aristotle University Thessaloniki Greece

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

Center for Dermatooncology Department of Dermatology Eberhard Karls University Tuebingen Germany

Department of Dermatology and Venereology Centro Hospitalar Universitário de Coimbra Coimbra Portugal

Department of Dermatology Erasme Hospital Université Libre de Bruxelles Brussels Belgium

Department of Dermatology Ghent University Hospital Ghent Belgium

Department of Dermatology Maastricht University Medical Center Maastricht Netherlands

Department of Dermatology Medical University of Vienna Austria

Department of Dermatology University Hospital Schleswig Holstein Campus Kiel Kiel Germany

Department of Dermatology University of Modena and Reggio Emilia Modena and Azienda Unità Sanitaria Locale IRCCS di Reggio Emilia Skin Cancer Centre Reggio Emilia 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 Oncology Odense University Hospital Denmark

Dermatology Clinic Maggiore Hospital University of Trieste Trieste Italy

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

Dermatology Unit University of Modena and Reggio Emilia Modena Italy

Institute of Dermatology Università Cattolica Rome and Fondazione Policlinico Universitario A Gemelli IRCCS Rome Italy

Medical and Surgical Dermatology Service Hospital Universitario Virgen Macarena Sevilla Spain

Melanoma Institute Australia The University of Sydney and Royal Prince Alfred Hospital Sydney New South Wales Australia

Melanoma Unit Department of Dermatology Hospital Clinic; IDIBAPS Barcelona Spain University of Barcelona Institut d'Investigacions Biomediques August Pi 1 Sunyer Centro de Investigación Biomédica en Red de Enfermedades Raras CIBERER Instituto de Salud Carlos 3 Barcelona Spain

Mount Vernon Cancer Centre Northwood UK

Nantes Université INSERM CNRS Immunology and New Concepts in ImmunoTherapy INCIT UMR 1302 EMR6001 Nantes F 44000 France

San Gallicano Dermatological Institute IRCCS Rome Italy

Skin Cancer Center Department of Dermatology Ruhr University Bochum Bochum 44791 Germany

The University of Manchester Oxford Rd Manchester M13 9PL UK

Twin Research and Genetic Epidemiology Unit School of Basic and Medical Biosciences King's College London London SE1 7EH UK

Université Paris Cite AP HP department of Dermatology INSERM U 976 Hôpital Saint Louis Paris France

University Department of Dermatology Université de Versailles Saint Quentin en Yvelines APHP Boulogne France

University Medical Center Utrecht and Princess Maxima Center Utrecht Netherlands; Comprehensive Cancer Center Munich of the Technical University Munich and the Ludwig Maximilians University Munich Germany

University of Perugia Unit of Medical Oncology Santa Maria della Misericordia Hospital Perugia Italy

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