Abstract
Background/Objectives: Lung cancer remains the leading cause of cancer-related mortality worldwide, with a high proportion of cases diagnosed at advanced stages. Accurate mediastinal staging is essential to guide optimal therapeutic decisions. This study aimed to evaluate the diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and to develop a composite clinical-molecular score (EXPoSURE) for risk stratification. Methods: A retrospective study was performed that included 131 patients diagnosed with lung cancer between December 2023 and December 2024 at a regional oncology center in Oltenia, Romania. All patients underwent bronchoscopy and EBUS-TBNA using a standardized protocol. Clinical, pathological, and molecular data were collected to assess diagnostic yield, staging performance, and the association with molecular markers. The EXPoSURE score integrated PD-L1, p63, EGFR status, comorbidities, histological type, and TNM stage. Results: EBUS-TBNA provided a conclusive diagnosis in 91.6% of cases, with a low rebiopsy rate of 8.4% and no requirement for mediastinoscopy. Most patients (68%) were diagnosed at stage IV. PD-L1, p63, and EGFR expression showed no significant correlation with TNM stage, while the EXPoSURE score demonstrated promising stratification capability. Occupational exposure appeared to influence disease severity in some subgroups, although further validation is needed. Conclusions: EBUS-TBNA is a valuable, safe, and effective approach for minimally invasive diagnosis and mediastinal staging of lung cancer. The proposed EXPoSURE composite score may contribute to a multidimensional risk assessment, supporting more tailored management strategies and warranting prospective validation.