Targeted bronchial washing fluid–based sequencing for detection of actionable genomic alterations in early-stage non–small cell lung cancer: A comparative analysis with plasma and surgical tissue.

Abstract

e20056 Background: In early-stage non–small cell lung cancer (NSCLC), plasma-based liquid biopsy has limited sensitivity due to low circulating tumor DNA shedding. This study evaluated the performance of targeted bronchial washing fluid (TBWF) as a tumor-proximal source for genomic profiling. Methods: This prospective observational study enrolled patients with clinical stage I–IIIA NSCLC undergoing diagnostic bronchoscopy followed by curative-intent surgical resection. Next-generation sequencing (NGS) was performed on TBWF, plasma, and matched surgical tissue specimens. The primary outcome was the detection rate of actionable genomic alterations (GAs) across specimen types. Secondary outcomes included concordance, co-occurring GAs, and procedural safety. Results: Among 52 patients with successful triplet NGS results, at least one actionable GA was identified in 79%. TBWF-based NGS detected actionable GAs in 69.2%, comparable to surgical tissue (71.2%; P = 0.830) and significantly higher than plasma (6%; P < .001). Concordance between TBWF and tissue was 83%, whereas concordance involving plasma was markedly lower. Across stages I–III, TBWF maintained detection rates comparable to tissue, while plasma showed marked stage dependence. Co-occurring GAs were detected more frequently in tissue (69%) than TBWF (44%). Targeted bronchial washing was safe, with only mild self-limited bleeding reported (17%). Conclusions: TBWF-based NGS provides reliable detection of actionable GAs in early-stage NSCLC, showing performance comparable to surgical tissue and clearly superior to plasma. TBWF may complement genomic profiling, particularly when preoperative tissue is limited.