Sequential versus massively parallel strategies for molecular characterization of non-small cell lung cancer samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration

Objectives: The advent of massively parallel next-generation sequencing (MP-NGS) offers potential advantages over sequential molecular profiling (SMP) in the management of non-small cell lung cancer (NSCLC). This study compares the two methodologies using samples obtained through endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), focusing on actionable mutation detection, turnaround time (TAT), and clinical outcomes. Methods: A retrospective analysis was conducted on NSCLC patients who underwent EBUS-TBNA and molecular characterization between January 2020 and December 2023. SMP and MP-NGS were compared in terms of actionable mutation detection rates, TAT, and impact on overall survival (OS). Results: Among 106 patients, MP-NGS demonstrated a significantly higher detection rate of actionable mutations compared to SMP (40.9% vs. 22.2%, p=0.042). The median TAT was slightly shorter with SMP than with externally outsourced MP-NGS (17 days vs. 23 days, p=0.076). Patients diagnosed via MP-NGS were more frequently allocated to targeted therapies (44.26% vs. 22.2%, p=0.038), which may have positively influenced overall survival (672 days vs. 138 days, p=0.053). Conclusion: MP-NGS provided superior diagnostic and clinical advantages over SMP in NSCLC, supporting its adoption as a standard diagnostic approach to enhance personalized therapy and improve patient outcomes.