Semin Respir Crit Care Med 2022; 43(04): 559-569
DOI: 10.1055/s-0042-1748185
Review Article

Management of Malignant Pleural Effusion: Where Are We Now?

Julien Guinde
1   Department of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, North University Hospital, Marseille, France
,
Hervé Dutau
1   Department of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, North University Hospital, Marseille, France
,
Philippe Astoul
1   Department of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, North University Hospital, Marseille, France
2   Aix-Marseille University, Marseille, France
› Author Affiliations

Abstract

Pleural malignancies are among the most common causes of pleural disease and form the basis of our daily pleural practice. There has been significant research and increase in both diagnostic and therapeutic management of malignant pleural diseases in the last decade. Good-quality data have led to a paradigm shift in the management options of pleural malignancies, and indwelling pleural catheter is now recommended and widely used as first-line intervention. Several trials compared different treatment modalities for pleural malignancies and continue to emphasize the need to reduce hospital length of stay and unnecessary pleural intervention, and the importance of patient choice in clinical decision making. This practical review aims to summarize the current knowledge for the management of pleural malignancies, and the understanding of the steps that we still have to climb to optimize management and reduce morbidity.



Publication History

Article published online:
25 May 2022

© 2022. Thieme. All rights reserved.

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  • References

  • 1 Boylan A, Broaddus V. Tumours of the pleura. Murray and Nadel's Textbook of Respiratory Medicine. 4th ed. Philadelphia, PA: Elsevier; 2019
  • 2 Thomas R, Francis R, Davies HE, Lee YCG. Interventional therapies for malignant pleural effusions: the present and the future. Respirology 2014; 19 (06) 809-822
  • 3 Porcel JM, Esquerda A, Vives M, Bielsa S. Etiology of pleural effusions: analysis of more than 3,000 consecutive thoracenteses. Arch Bronconeumol 2014; 50 (05) 161-165
  • 4 Sahn SA. Pleural diseases related to metastatic malignancies. Eur Respir J 1997; 10 (08) 1907-1913
  • 5 Porcel JM, Gasol A, Bielsa S, Civit C, Light RW, Salud A. Clinical features and survival of lung cancer patients with pleural effusions. Respirology 2015; 20 (04) 654-659
  • 6 Clive AO, Kahan BC, Hooper CE. et al. Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score. Thorax 2014; 69 (12) 1098-1104
  • 7 Psallidas I, Kanellakis NI, Gerry S. et al. Development and validation of response markers to predict survival and pleurodesis success in patients with malignant pleural effusion (PROMISE): a multicohort analysis. Lancet Oncol 2018; 19 (07) 930-939
  • 8 Fortin M, Taghizadeh N, Tremblay A. Procedures performed during hospitalizations for malignant pleural effusions: data from the 2012 National Inpatient Sample. Respiration 2018; 95 (04) 228-234
  • 9 Dipper A, Jones HE, Bhatnagar R, Preston NJ, Maskell N, Clive AO. Interventions for the management of malignant pleural effusions: a network meta-analysis. Cochrane Database Syst Rev 2020; 4: CD010529
  • 10 Heffner JE, Klein JS. Recent advances in the diagnosis and management of malignant pleural effusions. Mayo Clin Proc 2008; 83 (02) 235-250
  • 11 Corcoran JP, Tazi-Mezalek R, Maldonado F. et al. State of the art thoracic ultrasound: intervention and therapeutics. Thorax 2017; 72 (09) 840-849
  • 12 Qureshi NR, Rahman NM, Gleeson FV. Thoracic ultrasound in the diagnosis of malignant pleural effusion. Thorax 2009; 64 (02) 139-143
  • 13 Porcel JM, Light RW. Pleural effusions. Dis Mon 2013; 59 (02) 29-57
  • 14 Gordon CE, Feller-Kopman D, Balk EM, Smetana GW. Pneumothorax following thoracentesis: a systematic review and meta-analysis. Arch Intern Med 2010; 170 (04) 332-339
  • 15 Mercaldi CJ, Lanes SF. Ultrasound guidance decreases complications and improves the cost of care among patients undergoing thoracentesis and paracentesis. Chest 2013; 143 (02) 532-538
  • 16 Jiang B, Li X-L, Yin Y. et al. Ultrasound elastography: a novel tool for the differential diagnosis of pleural effusion. Eur Respir J 2019; 54 (02) 1802018
  • 17 Dresler CM, Olak J, Herndon II JE. et al; Cooperative Groups Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, North Central Cooperative Oncology Group, Radiation Therapy Oncology Group. Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion. Chest 2005; 127 (03) 909-915
  • 18 Feller-Kopman DJ, Reddy CB, DeCamp MM. et al. Management of malignant pleural effusions. an official ATS/STS/STR clinical practice guideline. Am J Respir Crit Care Med 2018; 198 (07) 839-849
  • 19 Martin GA, Kidd AC, Tsim S. et al. Inter-observer variation in image interpretation and the prognostic importance of non-expansile lung in malignant pleural effusion. Respirology 2019; DOI: 10.1111/resp.13681.
  • 20 Salamonsen MR, Lo AKC, Ng ACT, Bashirzadeh F, Wang WYS, Fielding DIK. Novel use of pleural ultrasound can identify malignant entrapped lung prior to effusion drainage. Chest 2014; 146 (05) 1286-1293
  • 21 Leung AN, Müller NL, Miller RR. CT in differential diagnosis of diffuse pleural disease. AJR Am J Roentgenol 1990; 154 (03) 487-492
  • 22 Porcel JM, Pardina M, Bielsa S, González A, Light RW. Derivation and validation of a CT scan scoring system for discriminating malignant from benign pleural effusions. Chest 2015; 147 (02) 513-519
  • 23 Porcel JM, Hernández P, Martínez-Alonso M, Bielsa S, Salud A. Accuracy of fluorodeoxyglucose-PET imaging for differentiating benign from malignant pleural effusions: a meta-analysis. Chest 2015; 147 (02) 502-512
  • 24 Vandemoortele T, Laroumagne S, Roca E. et al. Positive FDG-PET/CT of the pleura twenty years after talc pleurodesis: three cases of benign talcoma. Respiration 2014; 87 (03) 243-248
  • 25 Davies HE, Davies RJO, Davies CWH. BTS Pleural Disease Guideline Group. Management of pleural infection in adults: British Thoracic Society Pleural Disease Guideline 2010. Thorax 2010; 65 (Suppl. 02) ii41-ii53
  • 26 Swiderek J, Morcos S, Donthireddy V. et al. Prospective study to determine the volume of pleural fluid required to diagnose malignancy. Chest 2010; 137 (01) 68-73
  • 27 Abouzgheib W, Bartter T, Dagher H, Pratter M, Klump W. A prospective study of the volume of pleural fluid required for accurate diagnosis of malignant pleural effusion. Chest 2009; 135 (04) 999-1001
  • 28 Arnold DT, De Fonseka D, Perry S. et al. Investigating unilateral pleural effusions: the role of cytology. Eur Respir J 2018; 52 (05) 1801254
  • 29 Pinelli V, Laroumagne S, Sakr L, Marchetti GP, Tassi GF, Astoul P. Pleural fluid cytological yield and visceral pleural invasion in patients with epithelioid malignant pleural mesothelioma. J Thorac Oncol 2012; 7 (03) 595-598
  • 30 Froudarakis ME, Plojoux J, Kaspi E. et al. Positive pleural cytology is an indicator for visceral pleural invasion in metastatic pleural effusions. Clin Respir J 2017; DOI: 10.1111/crj.12619.
  • 31 Barlesi F, Mazieres J, Merlio J-P. et al; Biomarkers France Contributors. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet 2016; 387 (10026): 1415-1426
  • 32 Carter J, Miller JA, Feller-Kopman D, Ettinger D, Sidransky D, Maleki Z. Molecular profiling of malignant pleural effusion in metastatic non-small-cell lung carcinoma. The effect of preanalytical factors. Ann Am Thorac Soc 2017; 14 (07) 1169-1176
  • 33 DeMaio A, Clarke JM, Dash R. et al. Yield of malignant pleural effusion for detection of oncogenic driver mutations in lung adenocarcinoma. J Bronchology Interv Pulmonol 2019; 26 (02) 96-101
  • 34 Liu N, Sun R-Z, Du J. et al. Comparison of epidermal growth factor receptor gene mutations identified using pleural effusion and primary tumor tissue samples in non-small cell lung cancer. Appl Immunohistochem Mol Morphol 2018; 26 (04) e44-e51
  • 35 Yang J, Lee O-J, Son S-M. et al. EGFR mutation status in lung adenocarcinoma-associated malignant pleural effusion and efficacy of EGFR tyrosine kinase inhibitors. Cancer Res Treat 2018; 50 (03) 908-916
  • 36 Carbone DP, Reck M, Paz-Ares L. et al; CheckMate 026 Investigators. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med 2017; 376 (25) 2415-2426
  • 37 Reck M, Rodríguez-Abreu D, Robinson AG. et al; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016; 375 (19) 1823-1833
  • 38 Mok TSK, Wu Y-L, Kudaba I. et al; KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet 2019; 393 (10183): 1819-1830
  • 39 Grosu HB, Arriola A, Stewart J. et al. PD-L1 detection in histology specimens and matched pleural fluid cell blocks of patients with NSCLC. Respirology 2019; 24 (12) 1198-1203
  • 40 PD-L1 expression in pleural effusions of pulmonary adenocarcinoma and survival prediction: a controlled study by pleural biopsy | Scientific Reports [Internet]. [cited 2019 Dec 11]. Accessed February 28, 2022 at: https://www.nature.com/articles/s41598-018-29156-5
  • 41 Heymann JJ, Bulman WA, Swinarski D. et al. PD-L1 expression in non-small cell lung carcinoma: comparison among cytology, small biopsy, and surgical resection specimens. Cancer Cytopathol 2017; 125 (12) 896-907
  • 42 Gandhi L, Rodríguez-Abreu D, Gadgeel S. et al; KEYNOTE-189 Investigators. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 2018; 378 (22) 2078-2092
  • 43 Lentz RJ, Shojaee S, Grosu HB. et al. The impact of gravity vs suction-driven therapeutic thoracentesis on pressure-related complications: the GRAVITAS Multicenter Randomized Controlled Trial. Chest 2019; DOI: 10.1016/j.chest.2019.10.025.
  • 44 Psallidas I, Yousuf A, Talwar A. et al. Assessment of patient-reported outcome measures in pleural interventions. BMJ Open Respir Res 2017; 4 (01) e000171
  • 45 Thomas R, Jenkins S, Eastwood PR, Lee YCG, Singh B. Physiology of breathlessness associated with pleural effusions. Curr Opin Pulm Med 2015; 21 (04) 338-345
  • 46 Lentz RJ, Lerner AD, Pannu JK. et al. Routine monitoring with pleural manometry during therapeutic large-volume thoracentesis to prevent pleural-pressure-related complications: a multicentre, single-blind randomised controlled trial. Lancet Respir Med 2019; 7 (05) 447-455
  • 47 Martin GA, Tsim S, Kidd AC. et al. Pre-EDIT: a randomized feasibility trial of elastance-directed intrapleural catheter or talc pleurodesis in malignant pleural effusion. Chest 2019; 156 (06) 1204-1213
  • 48 Martin GA, Tsim S, Kidd AC. et al. Pre-EDIT: protocol for a randomised feasibility trial of elastance-directed intrapleural catheter or talc pleurodesis (EDIT) in malignant pleural effusion. BMJ Open Respir Res 2018; 5 (01) e000293
  • 49 Bibby AC, Dorn P, Psallidas I. et al. ERS/EACTS statement on the management of malignant pleural effusions. Eur Respir J 2018; 52 (01) 1800349
  • 50 Rahman NM, Gleeson FV. Image-guided pleural biopsy. Curr Opin Pulm Med 2008; 14 (04) 331-336
  • 51 Maskell NA, Gleeson FV, Davies RJO. Standard pleural biopsy versus CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. Lancet 2003; 361 (9366): 1326-1330
  • 52 de Fonseka D, Underwood W, Stadon L. et al. Randomised controlled trial to compare the diagnostic yield of positron emission tomography CT (PET-CT) TARGETed pleural biopsy versus CT-guided pleural biopsy in suspected pleural malignancy (TARGET trial). BMJ Open Respir Res 2018; 5 (01) e000270
  • 53 Diacon AH, Schuurmans MM, Theron J, Schubert PT, Wright CA, Bolliger CT. Safety and yield of ultrasound-assisted transthoracic biopsy performed by pulmonologists. Respiration 2004; 71 (05) 519-522
  • 54 Chang DB, Yang PC, Luh KT, Kuo SH, Yu CJ. Ultrasound-guided pleural biopsy with Tru-Cut needle. Chest 1991; 100 (05) 1328-1333
  • 55 Harris RJ, Kavuru MS, Rice TW, Kirby TJ. The diagnostic and therapeutic utility of thoracoscopy: a review. Chest 1995; 108 (03) 828-841
  • 56 Rahman NM, Ali NJ, Brown G. et al; British Thoracic Society Pleural Disease Guideline Group. Local anaesthetic thoracoscopy: British Thoracic Society Pleural Disease Guideline 2010. Thorax 2010; 65 (Suppl. 02) ii54-ii60
  • 57 Menzies R, Charbonneau M. Thoracoscopy for the diagnosis of pleural disease. Ann Intern Med 1991; 114 (04) 271-276
  • 58 Boutin C, Rey F. Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Part 1: Diagnosis. Cancer 1993; 72 (02) 389-393
  • 59 Froudarakis ME, Anevlavis S, Marquette C-H, Astoul P. Medical thoracoscopy implementation after a European Respiratory Society Course Held from 2003 to 2016: a survey. Respiration 2021; 100 (06) 523-529
  • 60 Bendixen M, Jørgensen OD, Kronborg C, Andersen C, Licht PB. Postoperative pain and quality of life after lobectomy via video-assisted thoracoscopic surgery or anterolateral thoracotomy for early stage lung cancer: a randomised controlled trial. Lancet Oncol 2016; 17 (06) 836-844
  • 61 Corcoran JP, Psallidas I, Hallifax RJ, Talwar A, Sykes A, Rahman NM. Ultrasound-guided pneumothorax induction prior to local anaesthetic thoracoscopy. Thorax 2015; 70 (09) 906-908
  • 62 Bedawi EO, Talwar A, Hassan M. et al. Intercostal vessel screening prior to pleural interventions by the respiratory physician: a prospective study of real world practice. Eur Respir J 2020; 55 (04) 1902245
  • 63 Thiam K, Guinde J, Laroumagne S. et al. Lateral decubitus chest radiography or chest ultrasound to predict pleural adhesions before medical thoracoscopy: a prospective study. J Thorac Dis 2019; 11 (10) 4292-4297
  • 64 Dhooria S, Singh N, Aggarwal AN, Gupta D, Agarwal R. A randomized trial comparing the diagnostic yield of rigid and semirigid thoracoscopy in undiagnosed pleural effusions. Respir Care 2014; 59 (05) 756-764
  • 65 Thomas R, Karunarathne S, Jennings B. et al. Pleuroscopic cryoprobe biopsies of the pleura: a feasibility and safety study. Respirology 2015; 20 (02) 327-332
  • 66 Quek JC, Tan QL, Allen JC, Anantham D. Malignant pleural effusion survival prognostication in an Asian population. Respirology 2020; 25 (12) 1283-1291
  • 67 Abisheganaden J, Verma A, Dagaonkar RS, Light RW. An observational study evaluating the performance of LENT score in the selected population of malignant pleural effusion from lung adenocarcinoma in Singapore. Respiration 2018; 96 (04) 308-313
  • 68 Chollet B, Guinde J, Laroumagne S, Dutau H, Astoul P. Does the LENT score risk-stratify patients with malignant pleural mesothelioma? An observational study. Thorac Cancer 2021; 12 (11) 1752-1756
  • 69 Brims FJH, Meniawy TM, Duffus I. et al. A novel clinical prediction model for prognosis in malignant pleural mesothelioma using decision tree analysis. J Thorac Oncol 2016; 11 (04) 573-582
  • 70 Rodriguez-Panadero F, Montes-Worboys A. Mechanisms of pleurodesis. Respiration 2012; 83 (02) 91-98
  • 71 Clive AO, Jones HE, Bhatnagar R, Preston NJ, Maskell N. Interventions for the management of malignant pleural effusions: a network meta-analysis. Cochrane Database Syst Rev 2016; (05) CD010529
  • 72 Rahman NM, Pepperell J, Rehal S. et al. Effect of opioids vs NSAIDs and larger vs smaller chest tube size on pain control and pleurodesis efficacy among patients with malignant pleural effusion: the TIME1 Randomized Clinical Trial. JAMA 2015; 314 (24) 2641-2653
  • 73 Janssen JP, Collier G, Astoul P. et al. Safety of pleurodesis with talc poudrage in malignant pleural effusion: a prospective cohort study. Lancet 2007; 369 (9572): 1535-1539
  • 74 Bhatnagar R, Piotrowska HEG, Laskawiec-Szkonter M. et al. Effect of thoracoscopic talc poudrage vs talc slurry via chest tube on pleurodesis failure rate among patients with malignant pleural effusions: a randomized clinical trial. JAMA 2020; 323 (01) 60-69
  • 75 Fysh ETH, Tremblay A, Feller-Kopman D. et al. Clinical outcomes of indwelling pleural catheter-related pleural infections: an international multicenter study. Chest 2013; 144 (05) 1597-1602
  • 76 Tremblay A, Michaud G. Single-center experience with 250 tunnelled pleural catheter insertions for malignant pleural effusion. Chest 2006; 129 (02) 362-368
  • 77 Putnam Jr JB, Light RW, Rodriguez RM. et al. A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis in the management of malignant pleural effusions. Cancer 1999; 86 (10) 1992-1999
  • 78 Thomas R, Fysh ETH, Smith NA. 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 (19) 1903-1912
  • 79 Warren WH, Kim AW, Liptay MJ. Identification of clinical factors predicting Pleurx catheter removal in patients treated for malignant pleural effusion. Eur J Cardiothorac Surg 2008; 33 (01) 89-94
  • 80 Fitzgerald DB, Muruganandan S, Tsim S. et al. Intrapleural fibrinolytics and deoxyribonuclease for treatment of indwelling pleural catheter-related pleural infection: a multi-center observational study. Respiration 2021; 100 (05) 452-460
  • 81 Van Meter MEM, McKee KY, Kohlwes RJ. Efficacy and safety of tunneled pleural catheters in adults with malignant pleural effusions: a systematic review. J Gen Intern Med 2011; 26 (01) 70-76
  • 82 Wahidi MM, Reddy C, Yarmus L. et al. Randomized trial of pleural fluid drainage frequency in patients with malignant pleural effusions. the ASAP trial. Am J Respir Crit Care Med 2017; 195 (08) 1050-1057
  • 83 Muruganandan S, Azzopardi M, Fitzgerald DB. et al. Aggressive versus symptom-guided drainage of malignant pleural effusion via indwelling pleural catheters (AMPLE-2): an open-label randomised trial. Lancet Respir Med 2018; 6 (09) 671-680
  • 84 Davies HE, Mishra EK, Kahan BC. et al. Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA 2012; 307 (22) 2383-2389
  • 85 Olfert JAP, Penz ED, Manns BJ. et al. Cost-effectiveness of indwelling pleural catheter compared with talc in malignant pleural effusion. Respirology 2017; 22 (04) 764-770
  • 86 Reddy C, Ernst A, Lamb C, Feller-Kopman D. Rapid pleurodesis for malignant pleural effusions: a pilot study. Chest 2011; 139 (06) 1419-1423
  • 87 Boujaoude Z, Bartter T, Abboud M, Pratter M, Abouzgheib W. Pleuroscopic pleurodesis combined with tunneled pleural catheter for management of malignant pleural effusion: a prospective observational study. J Bronchology Interv Pulmonol 2015; 22 (03) 237-243
  • 88 Bhatnagar R, Keenan EK, Morley AJ. et al. Outpatient talc administration by indwelling pleural catheter for malignant effusion. N Engl J Med 2018; 378 (14) 1313-1322
  • 89 Ahmed L, Ip H, Rao D, Patel N, Noorzad F. Talc pleurodesis through indwelling pleural catheters for malignant pleural effusions: retrospective case series of a novel clinical pathway. Chest 2014; 146 (06) e190-e194
  • 90 Tremblay A, Kearney CT, Hanks C. et al. Local and systemic effects of a silver nitrate coated indwelling pleural catheter in an animal model of pleurodesis. Exp Lung Res 2017; 43 (9-10): 388-394
  • 91 Bhatnagar R, Zahan-Evans N, Kearney C. et al. A novel drug-eluting indwelling pleural catheter for the management of malignant effusions. Am J Respir Crit Care Med 2018; 197 (01) 136-138