The Use of "Cancer Ratio" in Differentiating Malignant and Tuberculous Pleural Effusions: Protocol for a Prospective Observational Study.

Background: Differentiating between tuberculosis and malignancy as the cause of an exudative lymphocyte predominant pleural effusion is difficult due to similarities in the cellular and biochemical characteristics of the pleural fluid in both conditions. Microbiological tests in tubercular pleural effusions have a poor diagnostic yield, and the long turnaround time for results prevents an early diagnosis. The diagnosis of malignant pleural effusion (MPE) is hampered by a variable yield of pleural fluid cytology and closed pleural biopsy and the fact that thoracoscopy may not be readily available or feasible in each patient. A key gap in the existing knowledge is the performance of the serum lactate dehydrogenase to pleural adenosine deaminase ratio (ie, "cancer ratio"; CR) in differentiating between tuberculous and MPE in a high tuberculosis prevalence country like India, although its use has been well established in Western literature. The CR may find a practical application in the community health care settings in low-income countries without ready access to biopsy.

Objective: This study aimed to evaluate the CR as a test to differentiate tubercular and malignant etiology in patients with an exudative lymphocyte predominant pleural effusion. Secondary objectives to be assessed include a comparison of CR to pleural fluid carcinoembryonic antigen in MPE and the association of histologic type of lung carcinoma to the CR positivity.

Methods: This hospital-based, prospective, observational study will include patients admitted with pleural effusion whose pleural fluid reports indicate a lymphocyte-predominant exudate. The ability of the CR to discriminate between tuberculous and MPE will be evaluated as a primary objective of this study. The performance of CR and pleural fluid carcinoembryonic antigen in the diagnosis of MPE will be compared using the receiver operating characteristics and area under the curve for both tests as a secondary objective. The association between a positive CR and histologic type of lung cancer will be analyzed as well.

Results: Data collection began in June 2022. As of March 24, 2024, we have recruited 22 patients. Outcomes of the study are expected at the end of 2024.

Conclusions: The results of this study will provide an objective basis for the use of CR in differentiating between tuberculosis and malignancy as the cause of an exudative lymphocyte predominant pleural effusion.

International Registered Report Identifier (irrid): DERR1-10.2196/56592.