Alexandre Harlé, Alexandre Harlé, Léa Payen, Alexandra Lespagnol, Nicolas Goardon, Juliette Albuisson, Marie-Christine Etienne-Grimaldi, Anne Pradines, Alexandre Atkinson, Simon Cabello Aguilar, Alain Morel, Etienne Rouleau, Juliette Albuisson, Alexandre Atkinson, Romain Boidot, Simon Cabello Aguilar, Céline Callens, Charline Caumont, Louise-Marie Chevalier, Sophie Cotteret, Clotilde Descarpentries, Julie Dremaux, Marie-Christine Etienne-Grimaldi, Marie-Dominique Galibert-Anne, Nicolas Goardon, Alexandre Harlé, Alexandre Harlé, Paul Hofman, Lucie Karayan‐Tapon, Ludovic Lacroix, Aude Lamy, Pierre‐Jean Lamy, Cédric Lemarechal, Jacqueline Lehmann‐Che, Alexandra Lespagnol, Jonathan Lopez, Alain Morel, Jean-Baptiste Oudart, Alexis Overs, Léa Payen, Anne Pradines, Anaïs Pujals, Etienne Rouleau, Isabelle Soubeyran, Gaëlle Tachon, Anne Tallet, Marie-Pierre Wissler
BACKGROUND: Circulating tumour DNA (ctDNA) testing by liquid biopsy has become a cornerstone of precision oncology, yet technical heterogeneity across laboratories continues to hamper reproducibility and clinical reliability. METHODS: To address this challenge, the Groupe Français de Cytogénétique Oncologique (GFCO) conducted the largest European Delphi consensus initiative to date on technical standardization of ctDNA analysis, involving 39 high-volume molecular platforms (71 % response rate). RESULTS: Using iterative anonymous surveys and live voting, we established 37 recommendations (≥80 % agreement) spanning pre-analytical, analytical, bioinformatics, and post-analytical phases. Key consensus points include mandatory use of unique molecular identifiers (UMIs) with preference for ligation-based incorporation (95-100 %), double centrifugation with high-speed second spin, systematic positive controls mimicking ctDNA characteristics, leukocyte aliquot preservation for clonal haematopoiesis evaluation, and explicit reporting of variant allele frequency, CHIP risk, and limitations of negative results. These recommendations demonstrate more than 90 % alignment with recent ESMO (2022), ELBS (2025), ISLB (2025), and AMP/CAP guidelines while providing more prescriptive, operationally oriented specifications on critical steps (e.g., UMI implementation, plasma storage, centrifugation parameters) that address real-world gaps repeatedly identified in European external quality assessment schemes. CONCLUSIONS: By offering a robust, ready-to-implement framework that complements and refines existing international standards, this consensus paves the way for broader harmonization of ctDNA testing across Europe and beyond, ultimately strengthening confidence in liquid biopsy results for routine diagnostic and theragnostic applications in oncology.