Liquid biopsy and cfDNA go mainstream
Comparative studies show liquid biopsy (cfDNA) is a viable alternative to tissue for detecting actionable biomarkers in advanced NSCLC, and cfDNA is growing as a tool for both malignant and benign disease monitoring. The trend pushes cytology labs to strengthen pre-analytic QA and molecular triage workflows. (cancernetwork.com) (contemporaryobgyn.net)
The NILE prospective study enrolled 282 newly diagnosed advanced NSCLC patients and found plasma NGS (Guardant360) identified guideline-recommended biomarkers in three times as many patients as physician-choice tissue testing and was concordant with tissue when both were available in >90% of cases, with median lab turnaround 9 days for plasma vs 15 days for tissue. (investors.guardanthealth.com) Guardant360® CDx received FDA clearance as the first NGS-based liquid biopsy companion diagnostic for NSCLC in 2020, and FoundationOne® Liquid CDx later received FDA companion diagnostic labeling (including a tepotinib indication) in November 2024, establishing regulatory precedent for plasma-based treatment selection. (fda.gov) International clinical guidance has shifted toward a “plasma‑first” option for many patients with suspected advanced, oncogene‑addicted NSCLC (IASLC consensus, 2021), and pooled real‑world/clinical analyses have reported faster time‑to‑treatment with plasma testing (examples: median time to treatment reported as 18 vs 31 days in one series and plasma TAT advantages of roughly 6–10 days in others). (ascopost.com) Preanalytic QA is now explicitly codified: the NCI’s evidence‑based cfDNA biospecimen guidance was revised (document date Feb 5, 2025), EDTA whole‑blood should generally be processed within ~2–4 hours to avoid genomic DNA contamination whereas formaldehyde‑free stabilizing blood tubes (eg, Streck Cell‑Free DNA BCT/Nucleic Acid BCT) preserve cfDNA profiles at room temperature for up to 7 days. (dctd.cancer.gov) Cytology labs must bake molecular triage into workflows by validating plasma‑compatible NGS platforms, documenting limits of detection and concordance against tissue per FDA/IFU performance data (example: FoundationOne Liquid CDx SSED details analytical sensitivity and concordance studies), and creating reflex order sets or MTB pathways to route inadequate tissue cases to plasma testing. (accessdata.fda.gov) cfDNA adoption beyond oncology is expanding: donor‑derived cfDNA surveillance (AlloSure) now underpins large registry and prospective programs—KOAR/AlloSure registry data cover 1,743 kidney transplant recipients across 56 U.S. centers—and prenatal cfDNA screening (NIPT) is endorsed by major obstetric bodies for early aneuploidy screening from ~10 weeks’ gestation. (businesswire.com)
