A large-scale retrospective study of 936 analytical records from 747 non-small cell lung cancer (NSCLC) patients demonstrates that droplet digital PCR (ddPCR) shows exceptionally high concordance with next-generation sequencing (NGS) for detecting EGFR mutations across diverse clinical specimen types, including fresh tumor tissue, formalin-fixed paraffin-embedded (FFPE) tissue, plasma-derived cell-free DNA (cfDNA), and pleural effusion supernatant. The overall positive percent agreement (PPA) between ddPCR and NGS was 98.82% (925/936; exact 95% CI, 97.91%–99.41%). Variant allele frequencies (VAFs) measured by the two methods were strongly correlated (Pearson's r = 0.975). The study also validated that pre-capture NGS libraries can serve as reliable surrogate templates for ddPCR when original DNA input is limited, offering a practical solution for low-input clinical scenarios. These findings position ddPCR as a robust complement to NGS for rapid, sensitive, and cost-effective EGFR mutation testing in precision oncology workflows.
