Diagnostic Performance of Liquid Biopsy Compared to Tissue Biopsy in Lung Cancer Genomics: A Systematic Review and Meta-analysis

Abstract

Background: Tissue biopsy is the standard method for genomic profiling in lung cancer, but it is invasive, may yield insufficient tissue, and often fails to capture tumor heterogeneity. Liquid biopsy, particularly through circulating tumor DNA (ctDNA), provides a minimally invasive alternative with the potential for real-time molecular monitoring.

Objective: To evaluate the diagnostic performance of liquid biopsy compared to tissue biopsy for detecting genomic mutations in lung cancer through systematic review and meta-analysis.

Methods: A systematic literature search of PubMed, Scopus, Web of Science, and Cochrane Library was conducted for studies published between January 2010 and October 2024. Studies comparing liquid biopsy with tissue biopsy in lung cancer patients were included. A random-effects model was used to pool sensitivity, specificity, and diagnostic odds ratio (DOR). Heterogeneity was assessed using the I² statistic.

Results: Thirty-two studies involving 6,210 lung cancer patients were included. Liquid biopsy demonstrated a pooled sensitivity of 0.78 (95% CI: 0.72-0.83) and specificity of 0.93 (95% CI: 0.89-0.96). The diagnostic odds ratio was 45.3 (95% CI: 28.1-73.0). Mutation-specific concordance was highest for EGFR (85%), followed by ALK (78%), KRAS (65%), and ROS1 (59%). Heterogeneity was moderate (I² = 56%). NGS-based liquid biopsy platforms showed higher diagnostic accuracy compared to PCR-based methods.

Conclusion: Liquid biopsy demonstrates high specificity and moderate sensitivity relative to tissue biopsy and serves as a valuable complementary tool for genomic profiling in lung cancer. It is particularly useful when tissue sampling is challenging and for monitoring treatment response and resistance mutations. However, it should not fully replace tissue biopsy until further improvements enhance its sensitivity. Future advancements should focus on assay standardization and prospective clinical integration.