Prognostic Impact of Pleural Effusion in Patients with Malignancy: A Systematic Review and Meta-Analysis

Abstract

Background: Pleural effusion is a common complication of tumors, but the exact role of pleural effusion in the prognosis of tumor still remain unclear. We aimed to systematically review the prognostic value of pleural effusion in cancer patients.

Methods: We did a systematic review and meta-analysis with a systematic literature search on five databases, including PubMed, Cochrane Library, Medline (accessed via OVID), Embase and Web of Science covering the time from the database creation to April 2, 2020. We included all cohort studies and case control studies with available overall survival and progression-free survival results for cancer patients with or without pleural effusion. The studies with patients below the age of 18 and study population less than 30 were excluded. We applied the Newcastle-Ottawa Scale to assess the study quality. Mantel-Haenszel method was used to calculate the pooled HR and 95% CI. Heterogeneity and publication bias were examined. Subgroup analysis and sensitivity analysis were performed.

Findings: A total of 12189 studies were identified by the search and 47 studies with 146117 patients were included in the analysis. For overall survival, the pooled data demonstrated that pleural effusion is a poor prognostic factor for tumor patients (HR 1·58, 95% CI 1·43-1·75; I² 94·8%). For subgroup analysis, pleural effusion is a poor prognostic factor for lung cancer patients (HR 1·44, 95% CI 1·35-1·54; I² 60·8%), hematological tumor patient (HR 2·79, 95% CI 1·63-4·77; I² 29·4%) and other kinds of tumor patients (HR 2·08, 95% CI 1·43-3·01; I² 55·1%). Only in malignant pleural mesothelioma patients, pleural effusion is not a prognostic factor (HR 1·72, 95% CI 0·79-3·71; I² 91·9%). Whether or not malignant effusion is clearly diagnosed, the results cannot be affected. For progression-free survival, pleural effusion is a poor prognostic factor for cancer patients (HR 1·61, 95% CI 1·28-2·03; I² 42·9%). We also observed that massive pleural effusion is a poor prognostic factor (HR 1·32, 95% CI 1·13-1·55; I² 58·0%) compared to minimal pleural effusion, but metachronous pleural effusion is not a poor prognostic factor (HR 1·29, 95% CI 0·60-2·76; I² 93·3%) compared to synchronous pleural effusion.

Interpretation: Whether or not malignant effusion is clearly diagnosed, pleural effusion has a poor prognostic value in tumor patients except malignant pleural mesothelioma. It is a prognostic risk factor both in OS and PFS. Massive pleural effusion patients have a worse prognosis than minimal pleural effusion patients. The time of discovery of pleural effusion is not a prognostic factor for tumor patients. However, future evidence of other pleural effusion characteristics such as bilateral pleural effusion or unilateral pleural effusion, bloody pleural effusion or no-bloody pleural effusion is still needed.

Funding Statement: This work was supported by grants from Beijing Municipal Administration of Hospitals’ Mission Plan (No. SML20150301), Beijing Nova program (Z171100001117015), Beijing Talents Foundation (2017000021223ZK38) and “1351 Talents Program” of Beijing Chao-Yang Hospital (WXZXZ-2017-01 and CYXX-2017-35).

Declaration of Interests: We declare no competing interests.