Clinical Practice Guidelines for Pleural Effusion and Bronchoalveolar Lavage Fluid-Based Circulating Tumor DNA Testing in Lung Cancer

Background: Pleural effusion (PE) and bronchoalveolar lavage fluid (BALF) are increasingly investigated as alternative sources of circulating tumor DNA (ctDNA) for lung cancer molecular testing. As specimen-collection sites are close to thoracic tumors, specimens may contain clinically informative concentrations of tumor-derived DNA. However, standardized recommendations for PE/BALF-based ctDNA testing remain limited; practical, consensus-based recommendations for this testing in lung cancer were developed. Methods: The guidelines were developed using a structured multistep process modeled on the recent blood-based ctDNA guidelines. A targeted systematic literature review and evidence appraisal were performed, a national practice survey assessed current implementation barriers in Korea, and draft recommendations were refined through a two-round Delphi consensus involving eight multidisciplinary experts. Results: Twenty-seven studies were included in the qualitative review; 26 directly informed formal evidence grading, whereas one mixed-body-fluid implementation study was retained for contextual reference. The evidence was dominated by PE studies, with substantially fewer BALF-specific investigations. In a national survey of 109 analyzable respondents, 23 (21.1%) reported implementation of PE/BALF-based ctDNA testing. Lack of standardized protocols, reimbursement barriers, and technical complexity were common obstacles. Fifteen recommendations were finalized across three domains: pre-analytical procedures (R1-R4), analytical aspects and validation/quality management (R5-R8), and result interpretation, reporting, and clinical application (R9-R15). All recommendations met consensus-in criteria in round 1; agreement stability was confirmed in round 2. Conclusions: These consensus-based recommendations practically guide the implementation, validation, reporting, and interpretation of PE/BALF-based ctDNA testing in lung cancer, while highlighting the need for further matrix-specific evidence, particularly for BALF.