Abstract
Background/Objectives: Malignant pleural effusions (MPEs) pose a significant challenge in clinical practice and exert a considerable socio-economic burden on the healthcare system, affecting approximately 1 million individuals annually. These effusions are a leading cause of debilitating dyspnea and a diminished quality of life among cancer patients, with distant metastasis to the pleural layers occurring in about 20% of cases during treatment. Methods: A cross-sectional, observational case-control study was conducted on 151 Bulgarian patients with a hydrothorax. The control group included 72 patients with benign diseases, confirmed via biopsy, with 38 having inflammatory and 34 non-inflammatory pleural effusions. The other 79 patients had malignant pleural involvement. These groups are representative of the main types of pleural pathology. Results: The study found that all of the tumor markers, except for PIVKA-II (Protein induced by vitamin K absence-II), showed statistically significant differences between the malignant and non-malignant patient groups, with CAE (carcinoembryonic antigen) and CA19-9 showing the most notable differences. The Receiver Operating Characteristic (ROC) analysis revealed that CA72-4 had the best ability to distinguish between the two groups, while PIVKA was the weakest, with optimal cut-off values for all of the relevant tumor markers being derived using the Youden index. Conclusions: In conclusion, our study highlights the transformative potential of pleural fluid tumor markers as precise and minimally invasive resources for distinguishing malignant from non-malignant pleural effusions. These findings pave the way for improved diagnostic accuracy and personalized clinical management, addressing a critical gap in the care of patients with pleural pathologies.