Abstract
Lung cancer remains the leading cause of cancer mortality worldwide, with most cases diagnosed at advanced stages. Conventional tissue biopsy is invasive, and low-dose CT (LDCT) screening-although effective-faces practical and logistical limitations. Liquid biopsy has emerged as a minimally invasive approach to capture tumor-derived material, including circulating tumor DNA (ctDNA), cells, and extracellular vesicles (EVs). Among EVs, exosomes and their microRNA (miRNA) cargo offer a stable, disease-specific signal. Airway-proximal fluids such as bronchial aspirate and bronchoalveolar lavage fluid (BALF) are in direct contact with the tumor microenvironment and may contain higher concentrations of tumor-derived exosomal miRNAs compared with blood. This review synthesizes the limited but promising evidence for exosomal miRNAs in bronchial aspirate and BALF as diagnostic and prognostic biomarkers in lung cancer, examines methodological and standardization challenges, and discusses potential integration into clinical workflows, with particular emphasis on Romania's lung cancer epidemiology and healthcare context. While only two primary studies in the last five years have explored BALF exosomal miRNAs, these data justify further multicenter investigations aligned with MISEV2023 guidelines. Integrating airway-proximal exosomal miRNA analysis into bronchoscopy procedures could enhance diagnostic precision in resource-limited health systems and support the transition towards personalized thoracic oncology.