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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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Amaral reports personal fees for advisory board membership from Delcath and Philogen; personal fees as an invited speaker from BMS, Neracare, Novartis and Pierre Fabre; personal fees for a writing engagement from CeCaVa and Medtrix; institutional fees as local principal investigator (PI) from Agenus Inc., AstraZeneca, BioNTech, BMS, HUYA Bioscience, Immunocore, IO Biotech, MSD, Pfizer, Philogen, Regeneron, Roche and University Hospital Essen; institutional fees as coordinating PI from Unicancer; institutional research grants from iFIT and Novartis; institutional funding from MNI - Naturwissenschaftliches und Medizinisches Institut, Neracare, Novartis, Pascoe, Sanofi and Skyline-Dx; non-remunerated membership of the American Society of Clinical Oncology (ASCO) and the Portuguese Society for Medical Oncology; and a role as clinical expert in the area of medical oncology for Infarmed. Dr. Arenberger reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Sanofi, outside the submitted work. Dr Basset-Seguin has nothing to disclose. Dr. Bastholt reports personal fees for advisory boards from Bristol Myers-Squibb, Pierre Fabre, Merck MSD, Novartis and Roche, outside the submitted work. Dr. Bataille has nothing to disclose.Dr. Brochez has nothing to disclose.Dr. del Marmol reports grants and personal fees from BMS, grants and personal fees from SANOFI, personal fees from LEO Pharma, grants and personal fees from ALMIRALL, outside the submitted work.Dr. Dreno reports personal fees from MSD, grants and personal fees from BMS, grants and personal fees from Roche, grants and personal fees from Fabre , outside the submitted work. Dr. Eggermont reports Consultant for: Agenus, Boehringer Ingelheim, BioInvent, BioNTech, Brenus, CatalYm, Eurobio, GenOway,IO Biotech, Imcheck, IQVIA, Merck&Co/MSD, Pfizer, QBiotics, Regeneron, Sairopa BV, ScanCell,Scorpion Therapeutics, Secarna, SkylineDx BV, Thermosome, Trained Immunity DiscoverySpeaker engagements: Merck/MSD, SkylineDx BVEquity: IO Biotech, Sairopa BV, SkylineDX BV. Dr. Fargnoli reports grants and personal fees from Almirall, personal fees from Leo Pharma, grants and personal fees from Janssen, personal fees from Novartis, personal fees from Lilly, personal fees from Sanofi, personal fees from UCB, personal fees from Abbvie, personal fees from AMGEN, personal fees from Pierre Fabre, grants and personal fees from Galderma, personal fees from Sun Pharma, personal fees from BMS, personal fees from Kyowa Kyrin, personal fees from Pfizer, personal fees from MSD, outside the submitted work.Dr. Forsea has nothing to disclose.Dr. Garbe reports personal fees from CeCaVa, personal fees from MSD, personal fees from NeraCare, personal fees from Philogen, outside the submitted work.Dr. Hauschild reports grants and personal fees from Amgen, grants and personal fees from BMS, grants and personal fees from MerckPfizer, grants and personal fees from MSD/Merck, grants and personal fees from Philogen, grants and personal fees from Pierre Fabre, grants and personal fees from Regeneron, personal fees from Roche, grants and personal fees from Sanofi-Genzyme, grants and personal fees from Novartis Pharma, personal fees from Eisai, personal fees from Immunocore, grants and personal fees from Replimune, personal fees from Seagen, personal fees from IO Biotech, personal fees from Dermagnostix, personal fees from Incyte, grants and personal fees from NeraCare, grants from Huya Biosciences, personal fees from Kyowa Kirin, personal fees from Highlight Therapeutics, personal fees from Iovance, personal fees from CureVac, personal fees from Xenthera, peronal fees from Agenus, personal fees from Almirall, and personal fees from Sun Pharma, outside the submitted work.Dr. Hoeller reports personal fees from Amgen, personal fees from Almirall, personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Pierre Fabre, personal fees from Roche, personal fees from Sanofi, outside the submitted work.Dr. Kandolf reports personal fees for advisory boards from Bristol Myers-Squibb, MSD, Novartis Roche, Janssen, Abbvie, outside the submitted work.Dr. Kaufmann reports other from Abbvie, other from Almirall, other from Amgen, other from Astra Zeneca, other from Bionteck, other from BMS, other from Galderma, other from Incyte, other from Janssen , other from Leo, other from MSD, other from Novartis, other from Pfizer, other from Roche, other from Sanofi, outside the submitted work.Dr. Kelleners-Smeets reports personal fees from Sanofi, personal fees from Novartis, personal fees from MSD, personal fees from Sun Pharma, outside the submitted work.Dr. Lallas reports personal fees from Avene, personal fees from MSD, personal fees from Regeneron, personal fees from BMS, outside the submitted work.Dr. Lebbe reports personal fees from MSD, personal fees from Pierre Fabre, personal fees from BMS, personal fees from Sanofi, personal fees from immunocore, outside the submitted work.Dr. Leiter reports personal fees from Regeneron, Sanofi, personal fees from MSD, personal fees from Novartis, Almirall Hermal, personal fees from Sun Pharma, outside the submitted work.Dr. Longo has nothing to disclose.Dr. Lorigan reports grants and personal fees from Pierre Fabre, personal fees from MSD, grants and personal fees from BMS, personal fees from MLA diagnostics, outside the submitted work.Dr. Malvehy reports grants and personal fees from Almirall, personal fees from MSD, personal fees from Pierre Fabre, grants from Philogen, grants from Castle biosciences, grants from BMS, grants and personal fees from ISDIN, grants and personal fees from La Roche Posay, non-financial support and other from Vivascope, non-financial support and other from Damae medical, non-financial support and other from Canfield, non-financial support and other from Fotofinder, outside the submitted work.Dr. Mandala reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Regeneron, personal fees from Sun Pharma, outside the submitted work.Dr. Moreno-Ramírez has nothing to disclose.Dr. Nathan reports personal fees from Novartis, grants and personal fees from Immunocore, personal fees from BMS, personal fees from SunPharma, personal fees from MSD, outside the submitted work;Dr. Pellacani has nothing to disclose.Dr. Peris reports personal fees from Abbvie, personal fees from Lilly, personal fees from Leo Pharma, personal fees from Sanofi, personal fees from Almirall, personal fees from Novartis, personal fees from Boehringer, personal fees from Amgen, outside the submitted work.Dr. Saiag reports personal fees from Novartis, MSD, NeraCare, BMS, Pierre Fabre, Merck, personal fees and grants from Damae Medical, outside the submitted work.Dr. Stockfleth has nothing to disclose.Dr. Stratigos reports personal fees from Sanofi, personal fees from Janssen CILAG, personal fees and non-financial support from Novartis, grants from Genesis Pharma, grants from Abbvie, grants and personal fees from BMS, personal fees from Regeneron, grants from Leo-Pharma, grants from Lilly, outside the submitted work.Dr. van Akkooi reports grants and personal fees from Amgen, personal fees from Bristol-Myers Squibb, personal fees from Novartis, personal fees from MSD-Merck, grants and personal fees from Merck-Pfizer, personal fees from Pierre Fabre, personal fees from Sanofi, personal fees from Sirius Medical, personal fees from 4SC, personal fees from Genmab, personal fees from Menarini Silicon Biosystems, from Skyline Dx, outside the submitted work.Dr. Vieira has nothing to disclose.Dr. Zalaudek reports personal fees from Philogen, personal fees from MSD, personal fees from Novartis, personal fees from Sanofi, personal fees from La Roche Posay, personal fees from Sunpharma, personal fees from Biogena, personal fees from Cieffe Derma, outside the submitted work., (Copyright © 2024. Published by Elsevier Ltd.)

This guideline was developed in close collaboration with multidisciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF) and the European Organization for Research and Treatment of Cancer (EORTC). Recommendations for the diagnosis and treatment of melanoma were developed on the basis of systematic literature research and consensus conferences. Cutaneous melanoma (CM) is the most dangerous form of skin tumor and accounts for 90 % of skin cancer mortality. The diagnosis of melanoma can be made clinically and must always be confirmed by dermoscopy. If melanoma is suspected, a histopathological examination is always required. Sequential digital dermoscopy and whole-body photography can be used in high-risk patients to improve the detection of early-stage melanoma. If available, confocal reflectance microscopy can also improve the clinical diagnosis in special cases. Melanoma is classified according to the 8th version of the American Joint Committee on Cancer classification. For thin melanomas up to a tumor thickness of 0.8 mm, no further diagnostic imaging is required. From stage IB, lymph node sonography is recommended, but no further imaging examinations. From stage IIB/C, whole-body examinations with computed tomography or positron emission tomography CT in combination with magnetic resonance imaging of the brain are recommended. From stage IIB/C and higher, a mutation test is recommended, especially for the BRAF V600 mutation. It is important to perform a structured follow-up to detect relapses and secondary primary melanomas as early as possible. A stage-based follow-up regimen is proposed, which in the experience of the guideline group covers the optimal requirements, although further studies may be considered. This guideline is valid until the end of 2026., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Amaral reports personal fees for advisory board membership from Delcath and Philogen; personal fees as an invited speaker from BMS, Neracare, Novartis and Pierre Fabre; personal fees for a writing engagement from CeCaVa and Medtrix; institutional fees as local principal investigator (PI) from Agenus Inc., AstraZeneca, BioNTech, BMS, HUYA Bioscience, Immunocore, IO Biotech, MSD, Pfizer, Philogen, Regeneron, Roche and University Hospital Essen; institutional fees as coordinating PI from Unicancer; institutional research grants from iFIT and Novartis; institutional funding from MNI - Naturwissenschaftliches und Medizinisches Institut, Neracare, Novartis, Pascoe, Sanofi and Skyline-Dx; non-remunerated membership of the American Society of Clinical Oncology (ASCO) and the Portuguese Society for Medical Oncology; and a role as clinical expert in the area of medical oncology for Infarmed. Dr. Arenberger reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Sanofi, outside the submitted work. Dr Basset-Seguin has nothing to disclose. Dr. Bastholt reports personal fees for advisory boards from Bristol Myers-Squibb, Pierre Fabre, Merck MSD, Novartis and Roche, outside the submitted work. Dr. Bataille has nothing to disclose. Dr. Brochez has nothing to disclose. Dr. del Marmol reports grants and personal fees from BMS, grants and personal fees from SANOFI, personal fees from LEO Pharma, grants and personal fees from ALMIRALL, outside the submitted work. Dr. Dreno reports personal fees from MSD, grants and personal fees from BMS, grants and personal fees from Roche, grants and personal fees from Fabre, outside the submitted work. A. Eggermont Consultant for: Agenus, Boehringer Ingelheim, BioInvent, BioNTech, Brenus, CatalYm, Eurobio, GenOway, IO Biotech, Imcheck, IQVIA, Merck&Co/MSD, Pfizer, QBiotics, Regeneron, Sairopa BV, ScanCell, Scorpion Therapeutics, Secarna, SkylineDx BV, Thermosome, Trained Immunity Discovery Speaker engagements: Merck/MSD, SkylineDx BVEquity: IO Biotech, Sairopa BV, SkylineDX BV. Dr. Fargnoli reports grants and personal fees from Almirall, personal fees from Leo Pharma, grants and personal fees from Janssen, personal fees from Novartis, personal fees from Lilly, personal fees from Sanofi, personal fees from UCB, personal fees from Abbvie, personal fees from AMGEN, personal fees from Pierre Fabre, grants and personal fees from Galderma, personal fees from Sun Pharma, personal fees from BMS, personal fees from Kyowa Kyrin, personal fees from Pfizer, personal fees from MSD, outside the submitted work. Dr. Forsea has nothing to disclose. Dr. Garbe reports personal fees from CeCaVa, personal fees from MSD, personal fees from NeraCare, personal fees from Philogen, outside the submitted work. Dr. Hauschild reports grants and personal fees from Amgen, grants and personal fees from BMS, grants and personal fees from MerckPfizer, grants and personal fees from MSD/Merck, grants and personal fees from Philogen, grants and personal fees from Pierre Fabre, grants and personal fees from Regeneron, personal fees from Roche, grants and personal fees from Sanofi-Genzyme, grants and personal fees from Novartis Pharma, personal fees from Eisai, personal fees from Immunocore, grants and personal fees from Replimune, personal fees from Seagen, personal fees from IO Biotech, personal fees from Dermagnostix, personal fees from Incyte, grants and personal fees from NeraCare, grants from Huya Biosciences, personal fees from Kyowa Kirin, personal fees from Highlight Therapeutics, personal fees from Iovance, personal fees from CureVac, personal fees from Xenthera, peronal fees from Agenus, personal fees from Almirall, and personal fees from Sun Pharma, outside the submitted work. Dr. Hoeller reports personal fees from Amgen, personal fees from Almirall, personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Pierre Fabre, personal fees from Roche, personal fees from Sanofi, outside the submitted work. Dr. Kandolf reports personal fees for advisory boards from Bristol Myers-Squibb, MSD, Novartis Roche, Janssen, Abbvie, outside the submitted work. Dr. Kaufmann reports other from Abbvie, other from Almirall, other from Amgen, other from Astra Zeneca, other from Bionteck, other from BMS, other from Galderma, other from Incyte, other from Janssen, other from Leo, other from MSD, other from Novartis, other from Pfizer, other from Roche, other from Sanofi, outside the submitted work. Dr. Kelleners-Smeets reports personal fees from Sanofi, personal fees from Novartis, personal fees from MSD, personal fees from Sun Pharma, outside the submitted work. Dr. Lallas reports personal fees from Avene, personal fees from MSD, personal fees from Regeneron, personal fees from BMS, outside the submitted work. Dr. Lebbe reports personal fees from MSD, personal fees from Pierre Fabre, personal fees from BMS, personal fees from Sanofi, personal fees from immunocore, outside the submitted work. Dr. Leiter reports personal fees from Regeneron, Sanofi, personal fees from MSD, personal fees from Novartis, Almirall Hermal, personal fees from Sun Pharma, outside the submitted work. Dr. Longo has nothing to disclose. Dr. Lorigan reports grants and personal fees from Pierre Fabre, personal fees from MSD, grants and personal fees from BMS, personal fees from MLA diagnostics, outside the submitted work. Dr. Malvehy reports grants and personal fees from Almirall, personal fees from MSD, personal fees from Pierre Fabre, grants from Philogen, grants from Castle biosciences, grants from BMS, grants and personal fees from ISDIN, grants and personal fees from La Roche Posay, non-financial support and other from Vivascope, non-financial support and other from Damae medical, non-financial support and other from Canfield, non-financial support and other from Fotofinder, outside the submitted work. Dr. Mandala reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Regeneron, personal fees from Sun Pharma, outside the submitted work. Dr. Moreno-Ramírez has nothing to disclose. Dr. Nathan reports personal fees from Novartis, grants and personal fees from Immunocore, personal fees from BMS, personal fees from SunPharma, personal fees from MSD, outside the submitted work; Dr. Pellacani has nothing to disclose. Dr. Peris reports personal fees from Abbvie, personal fees from Lilly, personal fees from Leo Pharma, personal fees from Sanofi, personal fees from Almirall, personal fees from Novartis, personal fees from Boehringer, personal fees from Amgen, outside the submitted work. Dr. Saiag reports personal fees from Novartis, MSD, NeraCare, BMS, Pierre Fabre, Merck, personal fees and grants from Damae Medical, outside the submitted work. Dr. Stockfleth has nothing to disclose. Dr. Stratigos reports personal fees from Sanofi, personal fees from Janssen CILAG, personal fees and non-financial support from Novartis, grants from Genesis Pharma, grants from Abbvie, grants and personal fees from BMS, personal fees from Regeneron, grants from Leo-Pharma, grants from Lilly, outside the submitted work. Dr. van Akkooi reports grants and personal fees from Amgen, personal fees from Bristol-Myers Squibb, personal fees from Novartis, personal fees from MSD-Merck, grants and personal fees from Merck-Pfizer, personal fees from Pierre Fabre, personal fees from Sanofi, personal fees from Sirius Medical, personal fees from 4SC, personal fees from Genmab, personal fees from Menarini Silicon Biosystems, from Skyline Dx, outside the submitted work. Dr. Vieira has nothing to disclose. Dr. Zalaudek reports personal fees from Philogen, personal fees from MSD, personal fees from Novartis, personal fees from Sanofi, personal fees from La Roche Posay, personal fees from Sunpharma, personal fees from Biogena, personal fees from Cieffe Derma, outside the submitted work., (Copyright © 2024. Published by Elsevier Ltd.)