Liquid biopsy in prostate cancer: A multidisciplinary expert consensus statement

Area of Science:

• Oncology
• Genetics
• Molecular Diagnostics

Background:

• Tissue biopsy limitations in metastatic castration-resistant prostate cancer (mCRPC) necessitate alternative methods for genetic testing.
• BRCA1/2 gene mutations are crucial biomarkers for PARP inhibitor therapy in mCRPC.

Purpose of the Study:

• To develop consensus recommendations for standardized BRCA1/2 testing using liquid biopsy in mCRPC.
• To address technical challenges in pre-analytical, analytical, and post-analytical workflows for liquid biopsy testing.

Main Methods:

• A multidisciplinary panel of 18 Italian experts convened to establish consensus recommendations.
• Virtual and on-site meetings were conducted to identify and address technical gaps.
• Statements were approved by at least 80% of panelists, reflecting current evidence and expert practice.

Main Results:

• Liquid biopsy for BRCA1/2 testing is widely adopted or imminent in Italian centers, despite standardization challenges.
• Key technical insights include the use of cfDNA-preserving tubes, optimal storage, high assay sensitivity (LoD <1.0%), and bioinformatic integration.
• Next-generation sequencing covering coding and flanking regions was preferred, with a proposed harmonized synoptic report structure.

Conclusions:

• Liquid biopsy integration enhances access to BRCA1/2 stratification for mCRPC patients, supporting PARP inhibitor therapy.
• Standardized liquid biopsy testing improves diagnostic consistency and clinical decision-making.
• This consensus aims to optimize the management of mCRPC through improved diagnostic accuracy and timely treatment initiation.