Arlinda Silva Prameswari (1), Fadhilah Arsyil (2), Dwiraras Radityawan (3), Erlina Krisdianita Novitasari (4)
General Background: Lung cancer remains a leading cause of malignancy related mortality worldwide, with non-small cell lung cancer as the predominant type. Specific Background: Tissue biopsy remains the diagnostic gold standard for NSCLC, yet its invasive procedure, limited sample availability, and reduced capacity to represent tumor heterogeneity restrict clinical utility. Knowledge Gap: Although liquid biopsy offers a minimally invasive molecular diagnostic alternative, its diagnostic performance compared with tissue biopsy remains debated. Aims: This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of liquid biopsy versus tissue biopsy in adult patients with NSCLC. Results: Following PRISMA guidelines, articles from PubMed, Scopus, ScienceDirect, and Cochrane Library published from 2016 to 2026 were reviewed, with study quality assessed using QUADAS-2 and analysis performed using RevMan 5.4. Fourteen studies involving 3,180 NSCLC subjects were included. Liquid biopsy showed sensitivity ranging from 70.0% to 91.5% with substantial heterogeneity, while specificity remained high from 93.5% to 100% with low heterogeneity. SROC analysis demonstrated excellent diagnostic performance with AUC above 0.90, and no significant publication bias was observed. Novelty: This review directly evaluates whether liquid biopsy can serve as an alternative diagnostic approach to tissue biopsy in NSCLC. Implications: Liquid biopsy may support, but not replace, tissue biopsy due to variable sensitivity across clinical settings and disease stages.
Highlights:
Keywords: Liquid Biopsy, Non-Small Cell Lung Cancer, Tissue Biopsy
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