NGS Demonstrates Higher Sensitivity Than PCR for Liquid Biopsy EGFR Mutation Detection in Treatment-Naïve NSCLC
Posted: Tuesday, January 20, 2026
Next-generation sequencing demonstrated higher diagnostic sensitivity than polymerase chain reaction–based assays for detecting epidermal growth factor receptor (EGFR) mutations in liquid biopsies compared with tissue biopsy for treatment-naïve patients with non–small cell lung cancer (NSCLC), according to a systematic review and meta-analysis published in Cancer Diagnosis & Prognosis.
The analysis evaluated the diagnostic performance of circulating tumor DNA (ctDNA) testing using liquid biopsy relative to matched tissue biopsy. Although tissue biopsy remains the reference standard for molecular profiling, liquid biopsy is increasingly used in NSCLC, particularly when tissue is insufficient or unavailable.
Investigators conducted a search of MEDLINE and LILACS to identify studies comparing liquid biopsy and tissue biopsy for EGFR mutation detection in treatment-naïve patients with NSCLC using either polymerase chain reaction–based methods or next-generation sequencing. Diagnostic accuracy metrics were pooled using a random-effects model.
Twelve studies comprising 1,314 patients met the inclusion criteria. Using tissue biopsy as the reference, pooled sensitivity for EGFR mutation detection via liquid biopsy was 69% (95% confidence interval [CI] = 62%–75%) with next-generation sequencing and 56% (95% CI = 46%–65%) with real-time quantitative polymerase chain reaction (RT-qPCR) testing. Specificity was 90% (95% CI = 84%–94%) for next-generation sequencing and 89% (95% CI = 66%–97%) for RT-qPCR.
Next-generation sequencing–based liquid biopsies also demonstrated stronger likelihood ratios, with a positive likelihood ratio of 6.9 and a negative likelihood ratio of 0.34, compared with a positive likelihood ratio of 5.1 and a negative likelihood ratio of 0.49 for RT-qPCR. These findings indicate improved rule-in performance and fewer false-negative results with next-generation sequencing.
“Next-generation sequencing outperforms RT-qPCR in sensitivity and positive likelihood ratio for EGFR mutation detection via liquid biopsy in patients with NSCLC prior to treatment, reinforcing its potential as a diagnostic tool,” the study authors concluded. Rafael Parra-Medina, MD, MSc, PhD, of the Fundación Universitaria de Ciencias de la Salud and the Instituto Nacional de Cancerología in Bogotá, Colombia, is the corresponding author for the published study.
Disclosure: The authors reported no conflicts of interest.
