Diagnostic Accuracy of Liquid Biopsy Versus Tissue Biopsy in Lung Cancer Genomics: A Systematic Review and Meta-Analysis

Abstract

Background

Lung cancer is the most frequently diagnosed malignancy and the leading cause of cancer-related mortality worldwide. Most patients present with advanced disease, when curative options are limited. Molecular profiling has transformed management, particularly in non-small-cell lung cancer (NSCLC), but standard tissue biopsy is invasive, sometimes unfeasible, and limited by tumour heterogeneity.

Objective

To systematically evaluate the diagnostic accuracy of liquid biopsy compared with tissue biopsy for detecting clinically relevant genomic alterations in lung cancer.

Methods

A systematic review and meta-analysis were conducted in accordance with PRISMA and PRISMA-DTA guidelines. PubMed, Embase, Web of Science and Cochrane Library were searched from inception to 15 July 2024. Studies comparing blood-based liquid biopsy (circulating tumour DNA or cell-free DNA) with tissue biopsy for lung cancer genomic testing and reporting sufficient data to calculate sensitivity and specificity were included. Risk of bias was assessed using QUADAS-2. Bivariate random-effects models were used to pool sensitivity, specificity and the area under the hierarchical summary receiver operating characteristic curve (HSROC).

Results

Twenty-three studies involving 6,217 patients met the inclusion criteria. Overall, liquid biopsy showed moderate sensitivity and high specificity relative to tissue biopsy. Pooled sensitivity was 0.72 (95% CI 0.66-0.78), pooled specificity was 0.90 (95% CI 0.86-0.93), and the HSROC area under the curve was 0.84 (95% CI 0.78-0.89). Sensitivity was higher in advanced-stage disease and in next-generation sequencing-based assays. Most studies had at least one QUADAS-2 domain rated as unclear or high risk of bias.

Conclusion

Liquid biopsy offers a minimally invasive approach to genomic profiling in lung cancer, with high specificity and acceptable sensitivity compared with tissue biopsy. At present, it should be used as a complementary tool rather than a universal replacement for tissue biopsy, particularly in early-stage disease. It is especially valuable when tissue is insufficient or unobtainable, or for longitudinal monitoring of treatment response and resistance. Further high-quality, standardised comparative studies are needed to refine its role in routine care.