A recent single-center study published in the Journal of Experimental & Clinical Cancer Research (JECCR) analyzed 102 matched liquid and tissue biopsy samples from patients with advanced non–small cell lung cancer (aNSCLC) at diagnosis. The researchers compared four on-site cell-free DNA (cfDNA) next-generation sequencing (NGS) assays and the role of cfDNA methylation testing was evaluated.

The study concluded that liquid biopsy-based NGS is a strong complement to tissue biopsy and a practical alternative when tissue is insufficient or unavailable. Adding cfDNA methylation analysis can further boost diagnostic clarity in select cases.

The PCC spoke with Professor Paul Hofman (Head, Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, University of Nice Sophia Antipolis, France), one of the authors of this study, to reveal some key insights on the uniqueness of the findings and how liquid biopsy is shaping the future of precision medicine.

Professor Hofman discussed how liquid biopsy has become an essential component of molecular testing in aNSCLC. In line with ASCO and ESMO recommendations, liquid biopsy should be used when tissue biopsy is unavailable, insufficient for NGS, or when tissue testing turnaround times are too long to support timely treatment decisions.

They emphasized that liquid biopsy acts both as a complementary and, when necessary, alternative approach to tissue testing, enabling faster access to actionable genomic information.

He also outlined key differences between NGS methodologies used in liquid biopsy:

• Amplicon-based sequencing is preferred when circulating tumor DNA (ctDNA) levels are low and rapid turnaround is required
• Hybrid capture sequencing offers greater sensitivity for detecting gene fusions, copy number variations, and amplifications, particularly with small to medium panel sizes

In the study, all platforms performed similarly for point mutation detection, but hybrid capture showed superior sensitivity for structural variants.

Quality assurance was highlighted as critical. Professor Hofman noted the need for laboratory accreditation, annual participation in external quality assessment (EQA) programs, and inter-laboratory validation to ensure accurate, reliable results.

Finally, he addressed broader issues of equitable access for liquid biopsy, noting that cost and infrastructure barriers vary widely across countries. Collaboration among stakeholders, improved reimbursement structures, and stronger patient advocacy are needed to expand access. According to Professor Hofman, wider adoption of liquid biopsy can improve overall and progression-free survival while also reducing healthcare costs by enabling more precise and timely care and management plans.