Malignant Pleural Effusion

Pleural effusion caused by cancer cells in the pleura (proven by cytology or biopsy). It is the cause of about one third to one half of exudative effusions in adults.

• Primary tumours: lung (about 35 to 40%, mostly adenocarcinoma), breast (about 15 to 25%), lymphoma (about 10%), ovarian, gastric, colorectal, renal, prostate and genitourinary tumours, mesothelioma (asbestos exposure; effusion in 90%), melanoma, and unknown primary (about 7 to 15%). In sub-Saharan Africa, Kaposi sarcoma with HIV and lymphoma are important causes.
• Mechanism: pleural metastases and tumour obstruction of lymphatic drainage, raised vascular permeability from tumour derived VEGF, mediastinal node obstruction and low oncotic pressure.
• Prognosis: median survival about 3 to 12 months (shortest in lung cancer and with low pleural pH and glucose, high LDH and poor performance status; longer in breast, ovarian cancer and lymphoma, which respond to systemic treatment).

• Progressive breathlessness (the commonest symptom), dry cough, chest pain or heaviness, weight loss, fatigue; some are asymptomatic.
• Signs: stony dullness, absent breath sounds and vocal resonance over the effusion, tracheal and mediastinal shift away from a large effusion (no shift suggests a fixed mediastinum, trapped lung, mesothelioma or bronchial obstruction), signs of the primary cancer.
• Differential diagnosis: tuberculous effusion, parapneumonic effusion, paramalignant effusion (pulmonary embolism, superior vena cava obstruction, post-obstructive pneumonia, radiation pleuritis, drug induced effusion from dasatinib, methotrexate and amiodarone), heart failure, nephrotic syndrome, hypoalbuminaemia, cirrhosis with hydrothorax, hypothyroidism, rheumatoid and lupus pleuritis, and chylothorax.
• Complications: respiratory failure, trapped lung after drainage, loculation, infection of drain or catheter, tract metastases, and re-expansion pulmonary oedema.

• Chest X-ray (opacity with meniscus; a massive effusion with shift). Thoracic ultrasound for fluid, septation, pleural nodularity and pleural thickening; contrast CT chest and abdomen for pleural nodularity, primary and nodes.
• Diagnostic pleural aspiration of at least 50 to 60 mL: protein, LDH, glucose, pH, cell count (lymphocyte predominance), adenosine deaminase, Xpert MTB/RIF, culture, and cytology with cell block and immunohistochemistry. Cytology is positive in about 60% on the first sample, rising by about 27% with a second and 5% with a third; negative cytology does not exclude cancer. Fluid is bloody in about half.
• Pleural tissue when cytology is negative and suspicion remains: ultrasound guided or CT-guided core pleural biopsy (sensitivity about 85 to 95% when pleura is thickened), or medical thoracoscopy (sensitivity 92 to 95%, with talc pleurodesis in the same procedure).
• Tumour markers in fluid have no reliable diagnostic role. Test for driver mutations (EGFR, ALK, ROS1) and PD-L1 on cell block or biopsy for lung adenocarcinoma; receptor status for breast cancer; flow cytometry for lymphoma.
• Blood tests: full blood count, creatinine, liver function, albumin, LDH, HIV test, coagulation (before biopsy or catheter).
• Assess performance status and prognosis, and estimate symptom benefit of drainage with a therapeutic thoracentesis before a definitive procedure.

• Asymptomatic effusion: observe and treat the cancer.
• Symptomatic effusion: therapeutic thoracentesis, removing up to 1.5 L at once (stop for cough, chest pain, dyspnoea, or at a pleural pressure of minus 20 cmH2O when manometry is used) to avoid re-expansion pulmonary oedema; check for relief of breathlessness and lung re-expansion on X-ray (non-expandable lung means pleurodesis will fail).
• Systemic therapy (effusion may respond): chemotherapy for chemosensitive tumours (lymphoma, small cell carcinoma, breast and ovarian cancer, germ cell tumours); targeted therapy for lung adenocarcinoma with mutations (osimertinib 80 mg daily for EGFR mutation); immunotherapy for suitable tumours. Treatment is directed by oncology.
• Recurrent effusion needing repeated drainage within 1 month, in a patient with expected survival greater than 1 month:
  • Indwelling pleural catheter (tunnelled 15.5 French) placed under local anaesthesia as a day case: drain 150 to 1000 mL every 1 to 2 days at first (daily for the first 2 weeks), then as symptoms need. Spontaneous pleurodesis occurs in about 40 to 50% (at a median of about 6 weeks), after which the catheter is removed when drainage is less than 50 mL on 3 consecutive drainings. It is preferred for trapped or partly expanded lung, patients who want to stay at home, or after failed pleurodesis. Complications: pleural infection (about 5%, treated with systemic antibiotics, with the catheter kept in place), catheter blockage (alteplase 2 mg in 20 mL saline instilled for 1 hour), loculation, tract metastasis (mesothelioma), pain, and chylothorax. Combined catheter with talc 4 g or 2 g instilled via the catheter raises pleurodesis to about 40 to 50% at 35 days.
  • Talc pleurodesis (for expandable lung): through a chest drain as slurry (4 to 5 g in 50 to 100 mL saline) or at medical thoracoscopy as poudrage (4 to 5 g, success about 80 to 90%), once lung is fully expanded and drainage is less than 150 mL/day. Premedicate with intrapleural lidocaine 3 mg/kg (maximum 250 mg) and give analgesia (ibuprofen 400 mg three times daily or morphine 2.5 to 5 mg); small bore drains (10 to 14 French) are as effective as large bore; clamp for 1 hour, then reopen and remove the drain 24 to 48 hours later when drainage is less than 150 mL/day. Fever and pain are common; acute respiratory distress is rare and linked to large talc doses with small particle size.
  • Pleurodesis agents with limited evidence or availability: bleomycin 60 units, doxycycline 500 mg in 50 mL saline, povidone iodine 2%.
  • Pleurectomy and decortication for fit patients with mesothelioma or trapped lung (evidence is limited, mortality about 5 to 10%); pleuroperitoneal shunt for non-expandable lung (evidence is limited).
  • Prophylactic radiotherapy to drain tracts in mesothelioma is not routinely recommended.
• Symptom palliation: oxygen for hypoxaemia, morphine 2.5 to 5 mg orally every 4 hours (or modified release 5 to 10 mg twice daily) for breathlessness, a handheld fan, benzodiazepines for anxiety (lorazepam 0.5 mg sublingually), dexamethasone 4 to 8 mg daily for appetite and pain, and palliative care involvement.
• Special groups:
  • HIV and Kaposi sarcoma: start antiretroviral therapy; liposomal doxorubicin 20 mg/m2 every 3 weeks or paclitaxel for pleural Kaposi sarcoma.
  • Lymphoma: systemic chemotherapy (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 with a maximum of 2 mg on day 1, and prednisolone 100 mg daily for 5 days, repeated every 21 days for 6 cycles) usually clears the effusion.
  • Pregnancy: rare; therapeutic drainage and multidisciplinary oncology planning.
  • Frail patients: repeated thoracentesis or a catheter for comfort rather than surgery.
• Red flags: rapid reaccumulation, hypoxaemia, tracheal shift with severe distress, catheter infection (fever, erythema, purulent drainage), chest wall tumour nodules at drain sites.
• Follow up: review at 1 to 2 weeks after a procedure, catheter care by community nurses, chest X-ray after pleurodesis, and oncology follow up by tumour type.