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.