The NGS and PCR-based Detection of EGFR Mutations in Liquid Biopsy: A Systematic Review and Meta-analysis Compared With Tissue Biopsy in Treatment-naïve Patients With Non-small Cell Lung Cancer

Background/Aim: Liquid biopsy (LB) has demonstrated value in managing non-small cell lung cancer (NSCLC) and is widely used for monitoring disease progression in multiple cancers. While the role of baseline circulating tumor DNA (ctDNA) is not yet fully understood, emerging evidence suggests that LB should be integrated into NSCLC management, as pre-treatment ctDNA levels show a strong prognostic association with clinical outcomes. This systematic review and meta-analysis evaluated the diagnostic accuracy of molecular methods including PCR-based assays and next-generation sequencing (NGS) in detecting epidermal growth factor receptor (EGFR) mutations by comparing LB and tissue biopsy in treatment-naive patients with NSCLC. Materials and Methods: A systematic search of MEDLINE and LILACS identified studies comparing matched LB and tissue biopsy in treatment-naive patients with NSCLC using polymerase chain reaction (PCR) or NGS. Sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated using a random-effects model. Results: Twelve studies with 1,314 patients met the inclusion criteria. Most participants were male (59.5%), had adenocarcinoma (82.2%), and stage IV disease (77%). Pooled sensitivity and specificity for NGS in LB were 69% [95% confidence interval (CI)=0.62-0.75] and 90% (95%CI=0.84-0.94), respectively. Regarding real time quantitative polymerase chain reaction (RT-qPCR) sensitivity was 56% (95%CI=0.46-0.65) and specificity 89% (95%CI=0.66-0.97). NGS yielded a PLR of 6.9 and NLR of 0.34; RT-qPCR had a PLR of 5.1 and NLR of 0.49. Conclusion: NGS outperforms RT-qPCR in sensitivity and PLR for EGFR mutation detection via LB in patients with NSCLC prior to treatment, reinforcing its potential as a diagnostic tool.