Pleural effusions associated with worse survival in non-small-cell lung cancer

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1. Pleural effusions were associated with worse survival in non-small-cell lung cancer (NSCLC), particularly when they arose in early stage disease.

Evidence rating level: 2 (Good)

Study Rundown: Malignant pleural effusion containing malignant cells helps to define metastatic staging of lung cancer; however, diagnostic thoracentesis and pleural biopsy are not recommended for minimal effusions of <10mm thickness. Therefore, minimal pleural effusions are not currently included in the staging of small-cell or non-small-cell lung cancer. The purpose of this study was to evaluate the relationship between minimal effusion and survival. Upon survival analysis of a large retrospective cohort, the authors found that a minimal pleural effusion was significantly associated with shorter survival time, particularly in early stage disease.

This study benefits from the large population enrolled and consideration of many potential prognostic variables. However, due to the retrospective nature of this study, many other potentially significant variables such as environmental factors could not be controlled for. Furthermore, all patients were enrolled from a single site, and the natural course of the pleural effusions in these patients was not closely followed.

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Relevant reading: The IASLC lung cancer stating project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumors

In-Depth [retrospective cohort study]: This study included a cohort of 2061 patients diagnosed with stage I to IV NSCLC at a single university hospital. Patients who underwent non-contrast chest CT scans or who did not undergo brain imaging or whole-body bone scans were excluded. They were then sorted into three groups based on chest CT scans: no pleural effusion, minimal pleural effusion (<10mm thick), and malignant pleural effusion. No pleural fluid evaluation was done in the minimal pleural effusion group. Survival analysis was then performed, prognostic variables including patient demographics, weight loss prior to diagnosis, hematology studies, stage migration, tumor-related variables, and treatment-related variables. There were a total of 1397 patients without pleural effusion, 272 with minimal pleural effusion, and 392 with malignant pleural effusion. The authors found that minimal pleural effusion was significantly associated with shorter survival time compared to patients without pleural effusion (7.7 versus 17.7 months, P < 0.001), even after adjustment for other prognostic variables (HR 1.4, 95% CI 1.21-1.62). Minimal pleural effusion had a higher prognostic impact in early versus advanced stage disease (P_interaction = 0.001). After analyzing the probable mechanisms of minimal effusion, pleural invasion or attachment as the cause was seen in 87.8% of patients and independently predicted worse survival (P = 0.03).

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