Malignant pleural effusions (MPEs) cause considerable morbidity for patients afflicted with cancer. Metastatic breast, lung, and ovarian cancers account for the majority of cases. An estimated 150,000 new patients are diagnosed annually with dyspnea secondary to MPE.^1,2 Initial malignant diagnosis can be established in 50% to 60% of patients by means of a therapeutic thoracentesis.^1,2 However, the malignant effusions often recur, and patients require long-term palliation. The ideal therapy permits expedient, low-cost management of the pleural effusion with minimal morbidity because many of these patients have terminal disease. Operative management includes drainage through the use of video-assisted thoracic surgery (VATS) techniques combined with sclerosis, as well as operative placement of indwelling drainage catheters.^2–4 The operative techniques are described in Chapter 120. Nonoperative management of MPEs, the focus of this chapter, includes systemic chemotherapy and several methods of mechanical drainage, which may be combined with pleural sclerosing agents.

Lung cancer is the leading cause of MPE and accounts for as many as 40% of cases, followed by metastatic breast (25%), ovarian (5%), and gastric cancers (5%). Another 10% of patients have lymphoma-induced effusions, leaving 10% without identifiable primary malignancy.^2,5 Metastatic pleural spread is a complex mechanism that requires a series of mutational events leading to the sequential expression and coordination of numerous growth factors and cell surface adhesion molecules.⁶

Pleural seeding either by direct tumor extension or by hematogenous or lymphangitic spread initiates a series of pathophysiologic events that cause the development of effusions. These mechanisms include (1) the production of angiogenic growth factors that cause increased vascular permeability, including vascular endothelial growth factor, among others, (2) lymphatic obstruction, which perturbs the normal absorption cycle of 2 to 3 L of pleural fluid daily, (3) direct production of fluid by the tumor, which often occurs with ovarian malignancies, and rarely, (4) tumor invasion and blockage of venous structures, which results in venous hypertension and the ensuing alternating Starling’s forces that culminate in the effusion.²

All or some of these mechanisms contribute to the effusion, which first causes fatigue and lack of interest in activities followed by dyspnea, the principal and most disturbing symptom. The dyspnea tends to be progressive, if untreated, and eventually leads to symptoms at rest, underscoring the need for palliative treatment. The severity or degree of symptoms is related to the underlying cardiopulmonary function, the size of the effusion, or the rate of accumulation. Large effusions compress the lung and alter chest wall compliance, which together cause shortness of breath not only by altering the breathing mechanics, that is, decreasing the forced expiratory volume in 1 second (FEV₁ ) and tidal volume, but also by stimulating neurologic reflexes that lead to a subjective and uncomfortable sense of shortness of breath.²

The development of MPE portends a dismal prognosis because it is a sign of advanced disease. After diagnosis, patients with MPE experience a median survival of only 4 to 6 months. Only 10% to 15% of patients survive beyond a year. Patients with lung and gastrointestinal malignancies have a worse survival rate than those who have breast or hematologic malignancies.²

The treatment of MPE remains an important and at times difficult therapeutic challenge. The primary goal of therapy is to treat patients palliatively by relieving their dyspnea. Careful consideration of multiple factors should determine the optimal therapy. These include performance status, extent of disease, patient comfort and desires, and anatomic factors such as the degree of lung entrapment.

Systemic Therapy

Chemotherapy and Radiation Therapy

Small pleural effusions usually can be treated by malignancy-specific chemotherapy and localized radiation therapy to the primary lung lesion when the effusion is negative for malignancy, especially for those with small-cell lung and breast carcinomas.² However, neither of these treatments is effective for moderate to large effusions, and treatment should proceed to local therapies based on symptomatic management. For a detailed discussion of chemotherapy and radiation therapy for lung cancer, see Chapters 88 and 90.

Local Therapy

Thoracentesis

All patients with pleural effusions should undergo therapeutic thoracentesis, if not for the initial diagnosis, then to determine the contribution of the effusion to the patient’s dyspneic symptoms. Radiologic assessment with chest x-ray or chest CT scan after thoracentesis can be helpful in determining the extent of the disease and the degree of lung entrapment. If symptoms improve after therapeutic thoracentesis, one is afforded additional time to contemplate a more permanent solution. Failure of symptom improvement should lead to a prompt search for alternative etiologies, such as pulmonary embolus, lymphangitic carcinomatosis, or trapped lung.^2,7

Thoracentesis is performed by catheter-directed aspiration of the pleural space. Large effusions usually do not need image guidance. However, ultrasound-guided catheter aspiration is useful for small to moderate pleural effusions to prevent complications such as pneumothorax or hemothorax, as well as to optimize fluid removal. Several commercial kits are available. The procedure entails the use of a commercial catheter-over-needle system. The catheter is placed through the skin, over a rib (to avoid the intercostal neurovascular bundle), and into the chest (Fig. 119-1). Placement is confirmed by fluid aspiration. Fluid is aspirated manually with a syringe or drawn into a vacuum suction container. Local anesthesia of the chest wall and parietal pleura usually is adequate for pain control in the awake patient.

Complications of these procedures include, as mentioned, pneumothorax from lung puncture or hemothorax from either intercostal vessel injury or injury to other intrathoracic vascular structures, liver, or splenic puncture, which is notably rare. Other complications include reexpansion pulmonary edema, which can occur after large-volume thoracentesis. The exact volume of pleural fluid one can withdraw without developing this condition is unknown, but 2 L is typically the limit for patients with trapped lung or a fixed mediastinum, in whom the pleural pressure increases more dramatically with suction.^2,7 The precise mechanism is unknown, and supportive measures with supplemental oxygen and occasionally diuretics usually will suffice. At times, especially in the elderly or medically compromised patient, the pulmonary edema is so severe that intubation and ventilatory management are required for several days.⁸

Patients with recurrent effusions after thoracentesis can be managed in several ways. Repeat thoracentesis is an option for patients with extremely poor life expectancy (<1 to 2 months) who are either unwilling to undergo further intervention or for whom the anticipated need for fluid removal does not exceed two or three additional treatments. For patients whose symptoms improve with initial thoracentesis, the treatment decision turns on whether the lung expanded after thoracentesis or remained trapped. If the lung expanded fully, the patient may undergo pleurodesis with a chemical sclerosant such as talc, doxycycline, or bleomycin, among many other agents.² This option is valid for patients who are medically fit enough to tolerate the inflammatory response that ensues after pleural installation, especially with talc. Talc pleurodesis has been associated with acute respiratory distress syndrome and death and hence must be used with extreme caution in the elderly or medically compromised patient with poor cardiac and pulmonary function.² Patients with trapped lung resulting from a long-standing or fibropurulent effusion with fibrin peel formation on the lung surface are not candidates for pleurodesis. Pleural apposition is not possible in this setting, and therefore, the pleural space cannot be obliterated with sclerosing agents. These patients should be managed with a long-term indwelling pleural catheter and possibly decortication if the malignancy is of sufficiently low grade and expected survival sufficiently long to warrant this approach. The treatment algorithm in Table 119-1 was created with the foregoing principles in mind.