Liquid biopsy in BALF is now suitable for clinical practice in patients with suspected NSCLC

Abstract

Introduction

An accurate molecular diagnosis prior to treatment initiation is increasingly important in earlier stage NSCLC where obtaining sufficient tissue to generate molecular data can be challenging. This study evaluates the diagnostic value of cell-free DNA (cfDNA) analysis from bronchoalveolar lavage fluid (BALF) obtained via a proximal bronchial flush in patients suspected of NSCLC. We assess its potential to improve molecular diagnosis and evaluate concordance with pathological diagnosis.

Methods

Patients undergoing endobronchial diagnostics with suspected NSCLC were included. BALF was collected during the procedure for liquid biopsy analyses. Results were compared with molecular diagnoses obtained from tissue samples collected from the primary tumor or suspected lymph nodes, and if neither available from other metastatic sites.

Results

93 BALF samples were analyzed: 77 from patients with a confirmed malignancy, 10 with benign disease and six with unknown diagnoses. In patients with confirmed malignancy, a pathogenic variant was detected in BALF in 75% of cases. BALF analysis reduced the proportion of patients without a molecular diagnosis in tissue prior to treatment by 50%. The median variant allele frequency (VAF) of mutations detected in BALF was 5.0%. In 68 evaluable cases, sensitivity (78%), specificity (67%), PPV (94%), and NPV (32%) were calculated using tissue-based molecular diagnosis as the gold standard.

Conclusion

This study demonstrates that liquid biopsy of BALF, obtained through proximal bronchial lavage, is feasible and ready to be implemented in any lung-focused clinic. BALF presents a valuable, minimal-invasive diagnostic option, with the potential to enhance lung cancer diagnostics and patient management.