Management Options for Malignant Pleural Effusions
By Ali I. Musani, MD and Esther L. Langmack, MD
Malignant pleural effusion (MPE) is a common complication of advanced malignancy. It is estimated that between 150,000 and 175,000 patients in the US develop MPE each year. In most cases, MPE signifies incurable disease with a poor prognosis, typically a mean length of survival of six months from the time of diagnosis, with the exception of breast and ovarian cancer, in which survival may be longer. Dyspnea, cough, and chest pain associated with MPE can be devastating to patients already in the final stages of illness.
Conventional tube thoracostomy with chemical pleurodesis is still the most common treatment for MPE, but it is associated with significant discomfort and usually about a week of hospitalization. Current clinical experience and published studies support the selection of a palliative, rather than curative, management strategy for many patients with MPE. Medical thoracoscopy with pleurodesis and tunneled pleural catheters (TPCs) are newer, minimally invasive techniques that can be highly effective in reducing symptoms, hospital days, and treatment costs. Video-assisted thoracic surgery (VATS) with pleurodesis and pleuroperitoneal shunts remain options for selected patients.
Etiology and Pathogenesis
Tumors that metastasize frequently to the mediastinal lymph nodes and lymphatics (e.g. lung, breast, ovary, and lymphoma) are associated with most MPEs. Lung cancer causes approximately 37% of all MPEs. Other malignancies associated with MPE include gastric cancer and cancer of unknown primary.
Most MPEs result from lymphatic obstruction by tumor, which renders the parietal pleura incapable of reabsorbing pleural fluid at a normal rate. Other mechanisms of MPE formation include direct tumor invasion of the pleura, hematogenenous tumor spread to the parietal pleura, and release of cytokines that increase vascular and pleural membrane permeability. The presence of malignant cells in the pleural fluid establishes the diagnosis of MPE.
Selecting a Management Strategy
The first step in the management of MPE is to determine if the patient achieves symptomatic benefit from therapeutic thoracentesis (Figure 1). Up to 50% of patients with MPE do not experience a significant improvement in dyspnea or exercise tolerance with thoracentesis because of comorbid conditions (e.g., COPD), or general debility from the malignancy. In these situations, there is limited utility to repeated thoracentesis, pleurodesis, or placement of a chronic drainage apparatus.
Patients who do experience symptomatic relief after pleural fluid removal fall into three categories: those without trapped lung, those with trapped lung, and those with pleural fluid loculations (Figure 1). Patient symptoms, functional status, caregiver support, life expectancy and tumor type must also be considered when selecting a management strategy (Table 1). For MPE associated with some tumor types (e.g., small cell lung cancer or breast cancer), chemotherapy may be all that is required to reduce the effusion, precluding any further intervention.
For patients who have only a few weeks or months to live, or who are unable or unwilling to undergo invasive procedures or hospitalization, repeated therapeutic thoracentesis might be an option. However, therapeutic thoracentesis is not optimal for the long-term control of MPE, as symptomatic MPE recurs on average 4-5 days after thoracentesis. Symptomatic, recurrent, and recalcitrant (to chemotherapy or radiation therapy) MPEs should be addressed with a definitive, palliative care plan.
Tube Thoracostomy and Pleurodesis
Tube thoracostomy and pleurodesis with a sclerosing agent is indicated for patients who do not have trapped lung or pleural fluid loculations. Standard chest tubes (18-24F) and small-bore catheters (10-12F) have been used successfully. The ideal sclerosing agent has yet to be identified, because no large, head-to-head, randomized clinical trials comparing different agents have been performed. Successful pleurodesis is achieved in 81-93% of patients with MPE, depending on the sclerosing agent used and the clinical study. In a Cochrane review and another systematic review of the literature, talc was the most effective sclerosant for preventing MPE recurrence.
Tube thoracostomy with pleurodesis typically requires an average hospital stay of 5-7 days, although “accelerated” pleurodesis protocols have been reported to be equally effective. Chest pain and fever are the most common complications of tube thoracostomy and pleurodesis.Rare complications include site infection, empyema, arrhythmias, cardiac arrest, and hypotension. Acute respiratory distress syndrome (ARDS) has been reported in 4-8% of patients after administration of small, non-calibrated talc preparations, which are believed to be absorbed into the systemic vasculature, thus causing systemic inflammation. Larger particle (mean particle size 20 microns, with no particles < 10 microns), calibrated talc preparations are now recommended for talc slurry and talc poudrage. When initial pleurodesis for MPE fails, there are several options. Repeated therapeutic thoracentesis would be indicated for a patient with short expected survival. Other options include another attempt at pleurodesis (via tube thoracostomy, medical thoracoscopy, or VATS), pleurectomy, pleuroperitoneal shunting, or placement of a TPC.
Medical thoracoscopy, also known as pleuroscopy, can be used to both diagnose and treat malignant and nonmalignant pleural effusions. It has a high diagnostic and therapeutic yield and can be performed with the patient under conscious sedation, without mechanical ventilation, making it appropriate for a relatively sick patient population. The pleuroscope, which resembles a flexible bronchoscope, is introduced through an 11-mm trocar inserted into the pleural space. Pleural fluid is evacuated through the pleuroscope, the pleural surfaces are visually inspected for tumor, and biopsies of the parietal pleura can be taken with instruments inserted through the pleuroscope’s working channel. Pleurodesis can then be performed, typically by talc poudrage, through the pleuroscope.
Talc poudrage performed during medical thoracoscopy has a mean pleurodesis success rate of greater than 80-90% in published studies. When compared to bedside tube thoracostomy with talc slurry, thoracoscopic talc poudrage was associated with fewer recurrences of MPE in a systematic review (RR, 0.21; 95% CI 0.05-0.93). In one study, the most common complications were pneumothorax (8.3%), followed by subcutaneous emphysema (5.3%), fever (3.6%), and pain (1.2%). Death, severe sepsis, pulmonary embolism, or hypercapnic coma occurred in 0.6% of patients.
Video-Assisted Thoracic Surgery
In contrast to medical thoracoscopy, VATS requires a higher level of surgical expertise, general anesthesia, and single-lung mechanical ventilation. It is contraindicated for patients who cannot tolerate single-lung ventilation and who have complex pleural adhesions or airway abnormalities that preclude intubation with a double-lumen endotracheal tube. Its main advantage over medical thoracoscopy is superior access to the pleural space, which provides the opportunity for adhesiolysis, mechanical pleurodesis (by abrasion of the pleura), and biopsy of the lung, visceral and/or parietal pleura. At the end of the procedure, a sclerosing agent can be insufflated into the pleural cavity. VATS with talc poudrage has a high rate of success (> 90%) on the first attempt and achieves long-term control of MPE.
Pleuroperitoneal shunts transfer pleural fluid from the pleural space into the peritoneal cavity when manually pumped. Pleuroperitoneal shunts may be considered for patients with trapped lung who are not candidates for decortication. This technique may be particularly suited to patients with refractory chylothorax, because it allows recirculation of chyle. Shunts are also an option for treating MPEs that have failed chemical pleurodesis. Palliation with pleuroperitoneal shunting was achieved in 80-90% of properly selected patients in two small case series.
The use of pleuropertioneal shunts for managing MPE has gradually fallen out of favor, largely because of difficulties with shunt failure. Shunt failure is most commonly related to clotting of the catheter. The mean duration of shunt patency ranges from 2.5 to 26 months in published studies. Shunt infections and the need for manual operation also limit use in patients with MPE.
Tunneled Pleural Catheters
Over the last decade, TPCs (Figure 2) have become a popular, minimally invasive approach for management of MPE. Tunneled pleural catheters can be placed using conscious sedation, in an outpatient setting, using a modified Seldinger technique. A valve at the proximal end of the catheter prevents fluid and air from traveling through the catheter until the drainage line and vacuum bottle are attached. A polyester cuff on the catheter induces granulation in the subcutaneous tunnel, which helps to secure it in place and prevent infection.
Drainage is typically performed every other day. It takes about 15 minutes and can be done by the patient, a family member, or visiting nurse. When pleural fluid output drops to less than 50 ml on three consecutive occasions, and the absence of pleural fluid is confirmed radiographically, pleurodesis is assumed and the catheter is removed.
In a randomized study comparing a TPC with conventional tube thoracostomy and pleurodesis with doxycycline, spontaneous pleurodesis developed in 46% of TPC patients after a median of 29 days (range 8-223 days), versus 54% of chemical pleurodesis patients. Similar improvements were observed in procedure-related pain, dyspnea relief, and quality of life between groups. Patients treated with TPCs required significantly (p < 0.001) fewer hospital days for the procedure (median 1 day vs. 6.5 days for chemical pleurodesis). Median survival was similar for both groups (87 days for TPC, 90 days for chemical pleurodesis). In a retrospective study, hospital charges for TPC outpatients were significantly lower than for inpatients treated with tube thoracostomy and pleurodesis (mean $3,339 ± 1,753 vs. $7,830 ± 4,497, p = 0.001).
The rate of complications associated with TPCs compares favorably with that observed with other management options. In a retrospective analysis of 250 TPC insertions for MPE, the most common complications were symptomatic pleural fluid loculation (8.4%), unsuccessful insertion (4.0%), and asymptomatic pleural fluid loculation (4.0%). The most severe complication was empyema (3.0%), which was observed at a rate comparable to that seen with thoracoscopic talc poudrage in other series.17,26 Pneumothorax occurred in 2.4% of TPC patients. Rare (< 2%) complications included cellulitis, recurrent fluid, catheter dislodgement, bleeding, pain necessitating catheter removal, and tumor seeding the insertion site.
Management options for MPE have expanded significantly over the last decade, especially with the growing use of minimally invasive techniques. It is now possible to provide individualized, effective palliation for MPE while minimizing patient discomfort and hospitalization time. Studies are underway to evaluate the safety and efficacy of new sclerosing agents, as well as intrapleural chemotherapy and gene therapy delivered via TPC. These advances may yield additional treatment options for MPE in the future.
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