Liquid Biopsy vs. Tissue Biopsy in Guiding Genomic-Based Therapy for Lung Cancer: A Systematic Review & Meta-Analysis

Abstract

Background: Precision medicine in lung cancer requires accurate genomic profiling to guide treatment decisions. While tissue biopsy is the established diagnostic standard, liquid biopsy has emerged as a minimally invasive alternative capable of capturing tumor heterogeneity and monitoring resistance mutations in real time.

Objectives: To systematically evaluate and compare the diagnostic accuracy and clinical utility of liquid biopsy versus tissue biopsy in guiding genomic-based therapy for lung cancer.

Methods: A systematic literature search was conducted across PubMed, Scopus, Embase, Web of Science, and Cochrane Library from January 2010 to June 2025. Studies assessing liquid biopsy (circulating tumor DNA/CTCs) versus tissue biopsy for genomic mutation detection relevant to targeted therapy selection were included. Meta-analysis was performed using a random-effects model to calculate pooled sensitivity, specificity, concordance, and impact on therapeutic outcomes.

Results: Twenty-seven eligible studies comprising 6,215 lung cancer patients were analyzed. The pooled sensitivity and specificity of liquid biopsy were 82% (95% CI: 77–86%) and 95% (95% CI: 92–97%), respectively, compared to tissue biopsy. Concordance between biopsy methods was 88%. Liquid biopsy demonstrated faster treatment initiation (7.3 vs. 19.2 days) and better detection of resistance mutations, particularly EGFR T790M (91% vs. 68%). Complication rates were significantly lower with liquid biopsy (1.8% vs. 9.5%).

Conclusion: Liquid biopsy is a reliable and non-invasive alternative for genomic profiling in lung cancer, particularly for resistance detection and treatment monitoring. A combined diagnostic strategy with tissue biopsy enhances precision therapy decision-making.