Liquid biopsy in solid tumours: expert opinion paper of the European society of pathology

Liquid biopsy (LBx), particularly plasma circulating tumour DNA (ctDNA) analysis, has become an important use case of molecular pathology in solid tumours. While tissue remains the cornerstone of diagnosis, ctDNA testing provides a minimally invasive alternative using repeatable source of tumour-derived genomic information that complements tissue analysis when samples are unavailable, insufficient, outdated, or unlikely to capture tumour heterogeneity and evolution. In this expert opinion paper, the European Society of Pathology (ESP) defines its vision for LBx implementation across Europe and reaffirms the central role of pathology in blood-based detection of genomic alterations in solid tumours. Two clinical models highlight current implementation of LBx into standard diagnostic work-up. In advanced non-small cell lung cancer (NSCLC), LBx enables rapid detection of actionable somatic genomic alterations, supports treatment decisions when tissue biopsy is not available/sufficient for molecular analysis, and identifies acquired resistance genomic alterations at progression. However, tissue remains essential for histological classification, PD-L1 assessment, recognition of histologic transformation, evaluation of tumour microenvironment, and molecular testing when comprehensive genomic profiling or confirmation of liquid biopsy findings is required. In metastatic breast cancer, LBx has become central to dynamic molecular management of patients with originally hormonally dependent disease. This paper also addresses key technical and interpretative challenges, including assay selection, next-generation sequencing, clonal haematopoiesis, tumour fraction, variant allele fraction, co-mutations, testing logistics, and quality assurance. Given heterogeneity in access to LBx testing across Europe, harmonized standards for validation, reporting, training, and equitable availability are urgently needed. Pathology laboratories have a central role in identifying somatic alterations in cancer tissue, and LBx is an obvious extension of this important task. An integrated morphological-molecular pathology assessment is needed to implement appropriate precision oncology strategies. Incorporation of specific professional personal profiles (molecular biologists, bioinformaticians) to pathology laboratories is therefore essential for such optimal approach.