Glenn Geidel, Nathan Fekade, Katharina Raabe, Daniel J. Smit, Laura Adam, Isabel Heidrich, Alessandra Rünger, Julian Kött, Tim Zell, Teresa Amaral, P.A. Ascierto, Pippa Corrie, Reinhard Dummer, Alexander Eggermont, J. Guo, Jessica C. Hassel, Mathilde Jalving, Douglas B. Johnson, Lidija Kandolf, John M. Kirkwood, Celeste Lebbé, R. Lee, Georgina V. Long, P. Lorigan, Josep Malvehy, Joanna Mangana, Peter Mohr, Sapna P. Patel, Helen Rizos, Caroline Robert, Dirk Schadendorf, Vernon K. Sondak, Inge Marie Svane, Alberto Julius Alves Wainstein, Jonathan S. Zager, Klaus Pantel, Axel Hauschild, Christoffer Gebhardt, Maureen J.B. Aarts, Ana Arance, Nethanel Asher, Jürgen C. Becker, Shailender Bhatia, Christian U. Blank, Matthew S. Block, Celine Boutros, Elizabeth M. Burton, Marcus Butler, Richard D. Carvajal, Diwakar Davar, Vasileios Dervenis, Marco Donia, Thomas Eigentler, Leslie A. Fecher, Pier Francesco Ferrucci, Andrea Forschner, Olivier Gaide, Caroline Gaudy-Marqueste, Iva Gavrilova, Isabella C. Glitza Oliva, Simone M. Goldinger, Mohamed A. Gouda, Stephan Grabbe, Emmanuella Guenova, Ralf Gutzmer, Christine Häfner, Omid Hamid, Hildur Helgadottir, Markus V. Heppt, Tina J. Hieken, Lotte L. Hoeijmakers, Christoph Höeller, John Hyngstrom, Celine Jacobs, A. Jalovcic-Suljevic, Sekwon Jang, Muhammad A. Khattak, Damien Kee, Helmut Kehrer, Peter Koelblinger, James Larkin, Peter Lau, Ulrike Leiter, Elisabeth Livingstone, Evan J. Lipson, Caterina Longo, Jason J. Luke, Vincent T. Ma, Mario Mandalà, Lara Valeska Maul, Laura Mazilu, Friedegund Meier, Tanja Mesti, E. Muñoz-Couselo, Yasuhiro Nakamura, Bart Neyns, Janja Ocvirk, Kristina Orlova, Ines Pires Da Silva, Aleksandar Popovic
BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker in melanoma, with higher sensitivity for tumor burden detection than conventional diagnostics. While well established in research, clinical routine implementation remains pending. Key global questions concern optimal clinical applications and barriers to adoption. METHODS: A web-based survey of 116 members of the Melanoma World Society Study Group assessed international expert opinions on ctDNA utility across predefined clinical scenarios. The questionnaire included 18 general questions on ctDNA use and 5 clinical vignettes with de-identified patient data and retrospectively obtained ctDNA results. RESULTS: ctDNA was rated most valuable for detecting minimal residual disease (mean score 3.63), surveillance of recurrent disease (3.85), and stage IV melanoma (3.82), with limited utility in early stages. Experts considered ctDNA superior to S100 and LDH for early relapse detection and identifying progressive disease. Most participants (80%) agreed that ctDNA correlates with radiographic response, and 82% favored its integration into routine follow-ups. In urgent high-tumor-burden settings, 82.8% would initiate BRAFi/MEKi therapy based on ctDNA if tissue analysis was pending, and 93.9% if unavailable. For central nervous system lesions, 62% did not support blood ctDNA, while 66% considered cerebrospinal fluid valuable. Pragmatic approaches with small to mid-size targeted panels and short turnaround times were preferred. Major barriers included the need for prospective trials (85%), standardized guidelines (83%), and reimbursement policies (82%). CONCLUSION: Key opinion leaders regarded ctDNA as a valuable adjunct selected melanoma scenarios. Validation through prospective studies, guideline development, and reimbursement frameworks are essential for broader clinical implementation.