Mesothelioma Update

By Mark Block, MD; and Alice M. Boylan, MD

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Pleurectomy/Decortication and Extrapleural Pneumonectomy

The goal of surgery with therapeutic intent is to remove all gross disease. EPP involves en bloc removal of the lung along with surrounding parietal pleura, pericardium, and diaphragm. P/D preserves the underlying lung while removing all gross disease from all pleural surfaces. These are technically challenging procedures that are generally undertaken only at centers with extensive experience and expertise. EPP adheres to the oncologic principle of en bloc complete resection. In contrast, P/D is a less morbid procedure that debulks tumor, potentially delaying disease progression and enhancing the response to subsequent therapy. Although the therapeutic benefit of these procedures is controversial, both provide effective palliation. P/D relieves dyspnea by restoring lung expansion, and relieves pain by removing tumor that invades the chest wall. EPP relieves pain through the same mechanism, and may improve dyspnea by removing a nonfunctional lung that creates a right-to-left shunt and hypoxia.

Both P/D and EPP are accomplished through an extended posterolateral thoracotomy. Previous talc pleurodesis is not a contraindication to either procedure. The sixth rib is removed and the parietal pleural is bluntly dissected away from the chest wall, extending up to the apex of the chest, down to the diaphragm, and over to the pericardium medially. A second, more inferior intercostal incision is usually needed to facilitate dissection at the level of the diaphragm. The diaphragm is dissected off the underlying peritoneum and removed with the specimen. With P/D, once the pericardium is encountered medially, the dissection plane is continued onto the surface of the lung, excising the visceral pleura. In contrast, with EPP, the hilar structures are divided intrapericardially, and the lung is removed en bloc with the pleura. With both procedures, a synthetic patch (Gore-Tex; WL Gore & Associates; Newark, DE) is used to reconstruct the diaphragm. After a right pneumonectomy, reconstruction of the pericardium is also required to prevent cardiac herniation into the right chest. Both EPP and P/D involve prolonged operative times and may generate significant blood loss. One important advantage of EPP over P/D is that, with removal of the lung, postoperative radiation therapy can be delivered in much higher doses.

Preoperative evaluation of patients considered for surgery includes a thorough assessment of tumor stage, cardiac function, and pulmonary function. Because both P/D and EPP are intended to remove all gross tumor, it is essential to confirm that tumor is confined to the hemithorax. Chest CT is the essential first step. MRI is preferred by some centers for assessment of transdiaphragmatic extension of tumor, and others request fluorodeoxyglucose positron emission tomography to identify mediastinal or extrathoracic metastatic disease. Recent experience indicating that mediastinal lymph node involvement is a poor prognostic sign, especially for patients with the sarcomatoid type of mesothelioma, has led the group at the Brigham and Women’s Hospital to recommend cervical mediastinoscopy as an essential part of the staging evaluation.¹⁶ In addition, because mesothelioma may recur intraperitoneally, that group performs laparoscopy prior to opening the chest. Because both P/D and EPP are extensive procedures that place stress on the heart, echocardiography should be performed to insure that cardiac function is normal. For those patients considered for EPP, adequate pulmonary function must also be assured. Generally, a predicted postoperative FEV₁ of 1.2 L is acceptable. Often, the measured values reflect diminished function of the affected lung, and a lung perfusion scan can provide a more accurate estimate of the effect of pneumonectomy.

EPP has been approached with trepidation because the early experience was marked by an unacceptably high mortality rate of 30%. However, advances in surgical, anesthetic, and critical care techniques have dramatically lowered this figure, and experienced centers now report mortality rates of < 4%.¹⁶ This is no different from the mortality rate for a standard pneumonectomy. The most common postoperative complication is atrial fibrillation, occurring in approximately 30% of patients.

Results of P/D and EPP. The therapeutic benefit of P/D and EPP remains controversial. There are no prospective comparisons of these two procedures, or of surgery vs medical management or supportive care. Without such studies, it is difficult to conclude that surgery imparts a survival benefit. In addition, all surgical series must be interpreted with acknowledgment of inherent selection bias for patients with earlier-stage disease and better performance status.

Despite these caveats, several large series suggest that P/D and EPP may provide a survival advantage for selected patients. In 1997, Pass and colleagues¹⁷ reported on results with 78 patients from the National Cancer Institute. Thirty-nine patients underwent P/D and 39 underwent EPP. Median survival times were 14.5 and 9.4 months, respectively, after P/D and EPP. A year earlier, Rusch and Venkatraman¹⁸ also found that P/D was associated with a longer median survival than EPP. In this series, 50 patients underwent P/D and 51 underwent EPP; median survival was 18 and 10 months, respectively. However, in a follow-up report in 1999, with an additional 130 patients, the same investigators found that there was no difference in median survival between EPP and P/D.¹⁹ In general, failure after P/D is local, while failure after EPP is extrathoracic. These results are consistent with the oncologic principles of the procedures, and underscore the difficulty in surgically eradicating mesothelioma.

Sugarbaker and colleagues¹⁶ at the Brigham and Women’s Hospital have pursued an organized program of EPP followed by chemotherapy and high-dose radiation therapy. Of the patients who survived surgery (176 of 183), median survival was 19 months and 2-year survival was 38%. Five-year survival was 15%. However, patients with an epithelial cell type, clean margins after resection, and negative lymph nodes had a 2-year survival rate of 68% and 5-year survival rate of 46%. These results are encouraging, but may reflect a significant component of selection bias. In their series, Sugarbaker and colleagues¹⁶ found that only 23% of patients undergoing surgery had involved mediastinal nodes. In contrast, Rusch and Ventrakaman¹⁹ reported an incidence of 57%, and Pass and colleagues¹⁷ found lymph node metastases in 79% of their patients.

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