The Diagnostic Accuracy of Liquid Biopsy in EGFR-Mutated NSCLC: A Systematic Review and Meta-Analysis of 40 Studies.

Epidermal growth factor receptor (EGFR) mutations are the most common carcinogenic driver mutations in non-small-cell lung cancer (NSCLC) patients, while invasive tissue biopsy has certain inherent defects. PubMed, Ovid Medline, Embase, and the Cochrane Library were systematically searched on January 4, 2020, using the keywords "liquid biopsy," "EGFR," and "NSCLC." The pooled sensitivity and specificity of EGFR mutations in paired tissue and blood were calculated. The accuracy was assessed by receiver operating characteristic curve. The meta-regression of the subgroup was performed to analyze the heterogeneity. Hazard ratio (HR) and 95% confidence interval (CI) were combined for evaluating the impact of EGFR mutation in tissue and liquid blood biopsy. A total of 40 studies with 5,995 patients were involved in the study. The pooled sensitivity was 68% (95% CI = 60-75%), and the specificity was 98% (95% CI = 95-99%). The diagnostic odds ratio was 88 (95% CI = 40-195), and the area under the curve was 0.91 (95% CI = 0.88-0.93). In the meta-regression, the sensitivity and specificity remain lower in the Asian studies than non-Asian studies (sensitivity: 66% vs. 73%, P  = 0.04; specificity: 96% vs. 97%, P  = 0.03, respectively). The EGFR mutation was associated with a better progression-free survival than wild type in both tissue (HR = 0.54, 95% CI = 0.34-0.85, P  = 0.007) and blood (HR = 0.81, 95% CI = 0.71-0.92, P  = 0.001) detection. Peripheral blood liquid biopsy had a better specificity for detecting EGFR mutation in NSCLC patients, while tissue biopsy still needs to be undertaken for negative blood biopsy patients due to its lower sensitivity.