Liquid biopsy in prostate cancer: A multidisciplinary expert consensus statement

Introduction: BRCA1/2 testing via liquid biopsy has emerged as a critical, minimally invasive alternative to tissue sampling in metastatic castration-resistant prostate cancer (mCRPC), especially in the context of insufficient, inadequate, or unavailable tumor material. Methods: A multidisciplinary panel of 18 Italian experts from 16 leading academic and clinical institutions convened to develop consensus recommendations on BRCA1/2 testing via liquid biopsy. Through virtual and on-site meetings, technical gaps in pre-analytical, analytical, and post-analytical workflows were identified and addressed. Statements were approved by ⩾80% of panelists and reviewed to reflect both current evidence and expert practice. Results: The survey confirmed widespread implementation or imminent adoption of liquid biopsy testing across Italian centers, despite persistent challenges in standardizing sample collection, testing management, preservation, and reporting. Key technical insights included the importance of cfDNA-preserving tubes, optimal storage conditions, assay sensitivity (LoD <1.0%), and bioinformatic integration for detecting low-frequency variants. Next-generation sequencing was unanimously preferred, with BRCA1/2 coverage extended to coding and flanking regions. A harmonized synoptic report structure was proposed to enhance clinical interpretability and facilitate oncologic decision-making. Conclusions: Despite limitations in tissue availability, the integration of liquid biopsy into a diagnostic algorithm, endorsed by both AIOM and ESMO guidelines, enables broader access to BRCA1/2 stratification and supports timely PARP inhibitor therapy. This consensus aims to improve diagnostic consistency and clinical outcomes in the management of mCRPC across Italy.