The cancer ratio plus in the differential diagnosis of pleural effusions: a scoping review of current evidence

Abstract

Introduction: Differentiating between malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE) remains challenging in clinical practice. The cancer ratio plus (CR+), a potential diagnostic tool calculated as serum lactate dehydrogenase/(pleural adenosine deaminase x pleural lymphocyte percentage) has emerged to address this diagnostic challenge. This scoping review maps the available evidence on its diagnostic performance. Materials and methods: We conducted a systematic search of PubMed, Scopus, and Web of Science databases from inception to April 2025. Eligible studies assessed the accuracy of CR+ in distinguishing MPE from TPE. Data on study design, cut-off values, sensitivity, specificity, area under the curve (AUC), and likelihood ratios were extracted and synthesized narratively. Results: Six studies comprising 881 patients were included. Reported cut-off values varied widely (5.7 - 41.0), as did sensitivity (74.3 - 97.6%) and specificity (36.6 - 94.1%). Most studies, however, reported good discriminatory power with AUC values generally above 0.80. The highest diagnostic accuracy was observed in one study, which reported a sensitivity of 97.6%, a specificity of 94.1%, and an AUC of 0.86. Differences in cut-off thresholds, study populations, local tuberculosis epidemiology, and laboratory methodology (particularly lymphocyte quantification) likely contributed to this heterogeneity. Conclusions: The CR+ appears promising as a non-invasive tool using routine parameters for differentiating MPE from TPE, but diagnostic performance varies across settings. The heterogeneity in optimal cut-off values highlights the need for local validation before clinical adoption. Future research should standardize methodology and assess its impact on decision-making and patient outcomes.