Malignant Pleural Effusion: Therapeutic Options and Strategies

Pleural adhesions and trapped lung also pose specific dilemmas. Pleural adhesions can create loculated fluid pockets, thereby complicating drainage by thoracentesis or TPC and hindering dispersal of pleurodesis agents. Adhesiolysis by medical thoracoscopy or VATS may be useful in these patients to free up the pleural space and improve efficacy of long-term drainage options or facilitate pleurodesis. Intrapleural administration of fibrinolytics, such as streptokinase and urokinase, has also been used for treatment of loculated effusions and may improve drainage of pleural fluid and lung re-expansion.^60-63 However routine use of intrapleural fibrinolytics with pleurodesis has not been shown to be beneficial. In a randomized comparison using intrapleural urokinase prior to pleurodesis for patients with septated malignant pleural effusions, no difference in pleurodesis outcomes were identified.⁶³ As a result, TPC is the preferred palliation approach for patients with trapped lung physiology.^51,59

Combination Strategies

Combinations of different therapeutic interventions are being evaluated as a means for patients to achieve long-term benefits from pleurodesis while minimizing hospitalization time. One strategy using simultaneous treatment with thoracoscopic talc poudrage and insertion of a large-bore chest tube and TPC has been shown to permit early removal of the chest tube and discharge home using the TPC for continued daily pleural drainage. This “rapid pleurodesis” strategy has an 80% to 90% successful pleurodesis rate, permitting removal of the TPC at a median of 7 to 10 days.^64,65 With this approach, median hospitalization length of stay was approximately 2 days. While there was no control arm in these early reports with limited sample sizes, the pleurodesis success rate and length of hospitalization compare favorably to other published studies. A prospective, randomized trial of TPC versus an outpatient regimen of talc slurry via TPC has also shown promise, with successful pleurodesis after 35 days in 43% of those treated with the combination of talc slurry and TPC compared to only 23% in those treated by TPC alone.²⁷

Another novel approach to obtain the benefits of both TPC and pleurodesis strategies is the use of drug-eluting TPC to induce inflammation and promote adhesion of the visceral and parietal pleura. An early report of slow-release silver nitrate (AgNO₃) –coated TPC demonstrated an encouraging 89% spontaneous pleurodesis rate after a median of 4 days in the small subgroup of patients with fully expandable lung.⁶⁶ Device-related adverse events were relatively high at 24.6%, though only one was deemed a serious adverse event. Additional studies of these novel and combination strategies are ongoing at this time.

Costs

While cost of care is not a consideration in the decision-making for individual patients, it is important from a systems-based perspective. Upfront costs for pleurodesis are generally higher due to the facility and hospitalization costs, whereas TPC have ongoing costs for drainage bottles and supplies. In a prospective, randomized trial of TPC versus talc pleurodesis, there was no appreciable difference in overall costs between the 2 approaches.⁶⁷ The cost of TPC was significantly less, however, for patients with a shorter survival of less than 14 weeks.

Readmissions

Subsequent hospitalization requirements beyond just the initial treatment for a MPE remains another significant consideration for this patient population. A prospective, randomized trial comparing TPC to talc pleurodesis demonstrated a reduction in total all-cause hospital stay for TPC, with a median all-cause hospitalization time of 10 days for patients treated with TPC compared to 12 days for the talc pleurodesis group.²⁰ The primary difference in the number of hospitalization days was due to a difference in effusion-related hospital days (median 1 versus 4 days, respectively), which was primarily comprised of the initial hospitalization. In addition, fewer patients treated with TPC required subsequent ipsilateral invasive procedures (4.1% versus 22.5%, respectively). However, it is important to note that the majority of all-cause hospital days were not effusion-related, demonstrating that this population has a high utilization of acute inpatient services for other reasons related to their advanced malignancy. In a study of regional hospitals in the United States, 38.3% of patients admitted for a primary diagnosis of MPE were readmitted within 30 days.⁶⁸ There was remarkably little variability in readmission rates among hospitals, despite differences in factors such as institution size, location, patient distribution, and potential practice differences. This suggests that utilization of palliation strategies for MPE are only one component related to hospitalization in this population. Even at the best performing hospitals, there are significant common drivers for readmission that are not addressed. Therefore, additional effort should be focused on addressing aspects of care beyond just the palliation of MPE that predispose this population to requiring frequent treatment in an acute care setting.