Technical recommendations from a large-scale French Delphi consensus: a step toward European harmonization of ctDNA analysis

BackgroundCirculating 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. MethodsTo address this challenge, the Groupe Franais de Cytogntique 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). ResultsUsing iterative anonymous surveys and live voting, we established 37 recommendations (80 % agreement) spanning pre-analytical, analytical, bioinformatics, and post-analytical phases.Key J o u r n a l P r e -p r o o f 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. ConclusionsBy 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.