The Association Between Pleural Fluid Exposure and Survival in Pleural Mesothelioma


      Most patients with malignant pleural mesothelioma (MPM) seek treatment with malignant pleural effusion (MPE). In vitro evidence suggests that MPE may not be a simple bystander of malignancy, but rather potentially has biological properties that improve cancer cell survival and promote cancer progression. If this is the case, MPE management may need to shift from current symptomatic strategies to aggressive fluid removal to impact survival.

      Research Question

      Is there an association between pleural fluid exposure and survival in MPM?

      Study Design and Methods

      Data from 761 patients who received a diagnosis of MPM between 2008 and 2018 were collected from patient medical records in three UK pleural units. Data included factors previously identified as influencing prognosis in MPM. Medical imaging was reviewed for presence, size, and duration of pleural effusion. Time-dependent covariate analysis of pleural fluid exposure and survival (model included weight loss, serum albumin, hemoglobin, MPM subtype, performance status, chemotherapy, and age) and multivariate Cox regression analysis of pleurodesis and survival were conducted.


      Median overall survival was 278 days (interquartile range, 127-505 days; 95% CI, 253-301 days). Pleural fluid exposure duration showed no association with survival (hazard ratio, 1.0; 95% CI, 1.0-1.0). Median survival was 473, 378, and 258 days with complete, partial, and no pleurodesis (P = .008).


      Pleurodesis success seems to be associated with improved survival; however, it is unclear whether duration of MPM exposure to pleural fluid is associated with survival within the limitations of this retrospective study. Future prospective studies are required to assess this potentially important mechanism.

      Graphical Abstract

      Key Words


      ECOG PS (Eastern Cooperative Oncology Group performance status), HR (hazard ratio), MPE (malignant pleural effusion), MPM (malignant pleural mesothelioma)
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        • Royal College of Physicians
        National mesothelioma audit report 2018 (audit period 2014-16).
        (Published June 21, 2018. Royal College of Physicians website)
        • Woolhouse I.
        • Bishop L.
        • Darlison L.
        • et al.
        British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma.
        Thorax. 2018; 73: i1-i30
        • Feller-Kopman D.J.
        • Reddy C.B.
        • DeCamp M.M.
        • et al.
        Management of malignant pleural effusions. An official ATS/STS/STR Clinical Practice Guideline.
        Am J Respir Crit Care Med. 2018; 198: 839-849
        • Cheah H.M.
        • Lansley S.M.
        • Varano Della Vergiliana J.F.
        • et al.
        Malignant pleural fluid from mesothelioma has potent biological activities.
        Respirology. 2017; 22: 192-199
        • Stathopoulos G.T.
        • Kollintza A.
        • Moschos C.
        • et al.
        Tumor necrosis factor-α promotes malignant pleural effusion.
        Cancer Res. 2007; 67: 9825-9834
        • Zebrowski B.K.
        • Yano S.
        • Liu W.
        • et al.
        Vascular endothelial growth factor levels and induction of permeability in malignant pleural effusions.
        Clin Cancer Res. 1999; 5: 3364-3368
        • Brims F.J.H.
        • Meniawy T.M.
        • Duffus I.
        • et al.
        A novel clinical prediction model for prognosis in malignant pleural mesothelioma using decision tree analysis.
        J Thorac Oncol. 2016; 11: 573-582
        • van Meerbeeck J.P.
        • Gaafar R.
        • Manegold C.
        • et al.
        Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada.
        J Clin Oncol. 2005; 23: 6881-6889
        • Vogelzang N.J.
        • Rusthoven J.J.
        • Symanowski J.
        • et al.
        Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.
        J Clin Oncol. 2003; 21: 2636-2644
        • Marinaccio A.
        • Nesti M.
        • Regional Operational Centers
        Analysis of survival of mesothelioma cases in the Italian register (ReNaM).
        Eur J Cancer. 2003; 39: 1290-1295
        • Milano M.T.
        • Zhang H.
        Malignant pleural mesothelioma: a population-based study of survival.
        J Thorac Oncol. 2010; 5: 1841-1848
        • Montanaro F.
        • Rosato R.
        • Gangemi M.
        • et al.
        Survival of pleural malignant mesothelioma in Italy: a population-based study.
        Int J Cancer. 2009; 124: 201-207
        • Musk A.W.
        • Olsen N.
        • Alfonso H.
        • et al.
        Predicting survival in malignant mesothelioma.
        Eur Respir J. 2011; 38: 1420-1424
        • Neumann V.
        • Rütten A.
        • Scharmach M.
        • Müller K.-M.
        • Fischer M.
        Factors influencing long-term survival in mesothelioma patients—results of the German mesothelioma register.
        Int Arch Occup Environ Health. 2004; 77: 191-199
        • Nojiri S.
        • Gemba K.
        • Aoe K.
        • et al.
        Survival and prognostic factors in malignant pleural mesothelioma: a retrospective study of 314 patients in the west part of Japan.
        Jpn J Clin Oncol. 2011; 41: 32-39
        • van der Bij S.
        • Koffijberg H.
        • Burgers J.A.
        • et al.
        Prognosis and prognostic factors of patients with mesothelioma: a population-based study.
        Br J Cancer. 2012; 107: 161-164
        • Light R.W.
        • Rogers J.T.
        • Cheng D.
        • Rodriguez R.M.
        Large pleural effusions occurring after coronary artery bypass grafting. Cardiovascular Surgery Associates, PC.
        Ann Intern Med. 1999; 130: 891-896
        • Cartaxo A.M.
        • Vargas F.S.
        • Salge J.M.
        • et al.
        Improvements in the 6-min walk test and spirometry following thoracentesis for symptomatic pleural effusions.
        Chest. 2011; 139: 1424-1429
        • Livingston M.H.
        • Mahant S.
        • Ratjen F.
        • et al.
        Intrapleural dornase and tissue plasminogen activator in pediatric empyema (DTPA): a study protocol for a randomized controlled trial.
        Trials. 2017; 18: 293
        • Misra H.
        • Dikensoy O.
        • Rodriguez R.M.
        • et al.
        Prevalence of pleural effusions post orthotopic heart transplantation.
        Respirology. 2007; 12: 887-890
        • Thomas R.
        • Fysh E.T.H.
        • Smith N.A.
        • et al.
        Effect of an indwelling pleural catheter vs talc pleurodesis on hospitalization days in patients with malignant pleural effusion: the AMPLE randomized clinical trial.
        JAMA. 2017; 318: 1903-1912
        • Fisher L.D.
        • Lin D.Y.
        Time-dependent covariates in the Cox proportional-hazards regression model.
        Annu Rev Public Health. 1999; 20: 145-157
        • Bibby A.C.
        • Halford P.
        • De Fonseka D.
        • Morley A.J.
        • Smith S.
        • Maskell N.A.
        The prevalence and clinical relevance of nonexpandable lung in malignant pleural mesothelioma. A prospective, single-center cohort study of 229 patients.
        Annals ATS. 2019; 16: 1273-1279
        • Martínez-Moragón E.
        • Aparicio J.
        • Sanchis J.
        • Menéndez R.
        • Cruz Rogado M.
        • Sanchis F.
        Malignant pleural effusion: prognostic factors for survival and response to chemical pleurodesis in a series of 120 cases.
        Respiration. 1998; 65: 108-113
        • Amin Z.
        • Iskandar S.D.
        • Sibli
        Prognostic factors of 30-day survival of patients with malignant pleural effusion.
        Indian J Palliat Care. 2017; 23: 321-324
        • Hassan M.
        • Mercer R.M.
        • Maskell N.A.
        • et al.
        Survival in patients with malignant pleural effusion undergoing talc pleurodesis.
        Lung Cancer. 2019; 137: 14-18
        • Korsic M.
        • Badovinac S.
        • Cucevic B.
        • Janevski Z.
        Talc pleurodesis improves survival of patients with malignant pleural effusions: case-control study.
        Wien Klin Wochenschr. 2015; 127: 963-969
        • Nasreen N.
        • Mohammed K.A.
        • Dowling P.A.
        • Ward M.J.
        • Galffy G.
        • Antony V.B.
        Talc induces apoptosis in human malignant mesothelioma cells in vitro.
        Am J Respir Crit Care Med. 2000; 161: 595-600
        • Lee P.
        • Sun L.
        • Lim C.K.
        • Aw S.E.
        • Colt H.G.
        Selective apoptosis of lung cancer cells with talc.
        Eur Respir J. 2010; 35: 450-452
        • Nasreen N.
        • Najmunnisa N.
        • Mohammed K.A.
        • et al.
        Talc mediates angiostasis in malignant pleural effusions via endostatin induction.
        Eur Respir J. 2007; 29: 761-769