High Prevalence of Superficial Metastases Supports Percutaneous Ultrasound-Guided Biopsy for Diagnosis and Molecular Profiling of Advanced Lung Cancer: Results from a Prospective Cohort

Background: Despite therapeutic advances, many patients with metastatic lung cancer still lack access to comprehensive molecular profiling, often due to inadequate biopsy samples. Percutaneous ultrasound-guided needle aspiration biopsy (US-NAB) from both lung and metastatic sites has shown promise in improving diagnostic and molecular profiling accuracy. However, data regarding its real-world utilization, diagnostic performance, and contribution to comprehensive molecular profiling in unselected patients with advanced lung cancer remain limited. Methods: We performed a secondary (post hoc) analysis of prospectively collected data from the Propheta Pro study, a prospective observational cohort of patients with advanced lung cancer. The aim of the present analysis was to assess patterns of invasive sampling procedures, with a particular focus on the prevalence of US-NAB utilization across histologic subtypes. We also assessed the diagnostic yield of US-NAB for cancer diagnosis, comprehensive genomic profiling, and PD-L1 expression. Results: Among the 348 patients enrolled, 123 (35.3%) underwent US-NAB, making it the most frequently utilized sampling technique overall and across individual histologic subtypes. Biopsy of metastatic sites was significantly more common than primary lung tumors (113, 91.9% versus 10, 8.1%; p < 0.001), with superficial metastases being the primary target (110, 89.4%). US-NAB demonstrated high diagnostic yields: 97% for histological diagnosis, 91.1% for comprehensive genomic profiling, and 95.8% for PD-L1 testing. Only two minor, self-limiting complications were observed. Conclusions: US-NAB is a highly effective yet underrecognized diagnostic option for advanced lung cancer, particularly given the high prevalence of accessible superficial metastases. Integrating US-NAB into interventional pulmonology services could enhance diagnostic and molecular profiling yields.