Tissue and Plasma NGS Are Complementary for Molecular Profiling in Advanced Non-Small Cell Lung Cancer: Real-World Concordance and Clinical Impact

Background: Comprehensive molecular profiling is increasingly important in advanced non-small cell lung cancer (NSCLC), but the integration of tissue- and plasma-based next-generation sequencing (NGS) and its real-world therapeutic impact remain uncertain. Methods: We conducted a retrospective single-center study of 205 patients with advanced NSCLC treated between January 2016 and January 2019 who underwent routine molecular testing and tissue- and/or plasma-based NGS. Concordance was assessed for clinically relevant genomic alterations, and the impact of NGS on treatment decisions was evaluated. Results: A total of 280 NGS assays were performed. NGS identified potentially actionable genomic alterations in 88 patients (42.9%); in 50 patients (24.4%), potentially actionable genomic alterations were identified by NGS relative to conventional molecular testing. Among 64 patients who underwent both tissue- and plasma-based NGS, overall agreement was 78.1%, with moderate concordance (κ = 0.533). NGS results led to a direct treatment modification in 23 patients (11.2%), including clinical trial enrollment, standard targeted therapy, or compassionate-use treatment. Conclusions: Tissue- and plasma-based NGS provided complementary rather than interchangeable genomic information. The difference between theoretical actionability and actual therapeutic impact highlights the importance of clinical context, timing of testing, and treatment availability when interpreting comprehensive genomic profiling in advanced NSCLC.