Choice of Surgical Treatment for Mesothelioma Remains Complex

Surgery for malignant pleural mesothelioma remains a complicated and controversial issue. Thus far, the benefits of surgery vs. nonsurgical treatment have yet to be demonstrated.

Complete resection with surgery alone (R0) appears theoretically unattainable since it is impossible to eradicate residual microscopic disease, regardless of the surgical method used. Hence, most surgical treatment today is coupled to various adjuvant treatments, primarily a trimodality mode with radiotherapy and chemotherapy, according to Dr. Raja M. Flores, professor and chief of thoracic surgery, Mount Sinai School of Medicine, New York.

A “curative” surgical procedure remains an elusive goal, and thus the focus of lung surgery for malignant pleural mesothelioma (MPM) has shifted to R1 surgical resection for cytoreduction in the hope of prolonging life, relieving symptoms, and enhancing the effectiveness of adjuvant therapies. This approach has often meant a shift from the more radical extrapleural pneumonectomy (EPP), when possible, to the more lung-sparing pleurectomy/decortication (PD) procedure, according to Dr. Flores (Sem. Thorac. Cardiovasc. Surg. 2009;21:149-53).

EPP involves a radical en bloc resection of the lung, pleura, diaphragm, and pericardium. PD involves resection of the parietal and visceral pleurae, pericardium, and – when necessary – the diaphragm, but it spares the entire lung. Both operations are technically complex and require extensive surgical expertise.

The operative mortality rate of EPP in the literature ranges from 4% to 15%, vs. and 1% to 5% for PD. In addition, PD has lower morbidity than does EPP. But the two techniques are not interchangeable, according to Dr. Flores. The choice of surgical technique depends on multiple factors, and the decision is often made at the time of surgery because the preoperative imaging may have underestimated the amount of disease present.

Staging is critical in determining the appropriate procedure, and the merits of each surgical approach have been debated in several recent clinical and registry trials examining individual mortality and morbidity of these procedures at different stages, coupled with the use of a variety of adjuvant therapies. However, many decisions are based on surgical conjecture and bias rather than scientific data.

Evidence indicates that PD provides a survival advantage for patients with stage I MPM, which may be accounted for by “lower mortality, lower postoperative adverse events, and greater lung capacity when relapse occurs,” according to Dr. Flores. However, he explained, most patients with mesothelioma will present at a stage that requires EPP to eradicate all gross disease. PD can provide an R1 resection in early-stage disease, but as the tumor enlarges and invades the lung, fissures, and costophrenic sulcus, a PD is suboptimal regardless of resection of the pericardium and diaphragm.

There is, however, a critical balance between optimal cytoreduction and morbidity that varies across stages for these two procedures. For stage II disease, there is a “trend toward improved survival for EPP, despite an inherently higher tumor stage than PD,” Dr. Flores said.

Stage III disease proved more complex, with similar survival data seen for both EPP and PD. Ultimately, “one should focus on obtaining a complete macroscopic resection based on the extent of tumor” for this stage of disease, choosing the best procedure accordingly, he advised.

For more advanced (stage IV) disease characterized by diffuse chest wall invasion and extensions through the diaphragm to the underlying peritoneum, the situation is much different.

“The tumor may be amenable to EPP, but there will be gross residual tumor left behind in the hemithorax. Because one of the most likely sites of recurrence is the contralateral pleura, the patient is better served by preserving lung function,” Dr. Flores explained.

In stage IV disease, PD trended toward better survival, presumably because “when disease spreads to the contralateral lung, PD or debulked patients will be less symptomatic and better functionally able to tolerate systemic therapy because of their greater pulmonary reserve,” he said.

“The goal is to remove all gross tumor while preserving as much of the lung as possible. Every patient and clinical situation is unique; therefore, treatment is difficult to generalize. Find an experienced mesothelioma surgeon you trust and leave it in their hands,” Dr. Flores said in an interview.

Ultimately, the situation remains complex. Dr. Heyman Luckraz of the New Cross Hospital, Wolverhampton, United Kingdom, and his colleagues recently reported results with 139 patients. EPP was chosen for clinically fit patients with stage I disease, while patients with advanced disease or who were unfit for EPP underwent PD. “EPP may only have a limited role in diffuse MPM, particularly as neither operative procedure is curative. Ultimately, the place of EPP will only be determined by randomized trial in comparison to PD in stage I disease with both groups receiving adjuvant therapy,” the investigators concluded (Eur. J. Cardio-Thorac. Surg. 2010;37:552-6).

Whether such trials will ever be performed is an open question. Despite the recent Mesothelioma and Radical Surgery (MARS) trial, which demonstrated the possibility of randomizing patients to surgical vs. nonsurgical treatment, there will likely never be a randomized clinical trial powered enough to completely solve the puzzle, according to Dr. Tom Treasure of the University College of London (Eur. J. Cardio-Thorac. Surg. 2010;37:509-10).

Efforts continue to develop surgical alternatives with less mortality and morbidity than those of the standard EPP and PD procedures. For example, Dr. M.D. Kluger and colleagues at Columbia University, New York, reported the phase I and II results of a recent clinical trial on a two-stage operative cytoreduction procedure coupled with intraperitoneal chemotherapy (Eur. J. Surg. Oncol. 2010;doi:10.1016/j.ejso.2010.07.001). They found that their protocol offered median survival comparable to that of one-stage protocols; rates of morbidity, mortality, visceral resections were relatively low and length of stay was relatively short despite the need for two operations.

Ultimately, surgery might be totally immaterial in some cases. In two recent papers, the type of surgery was not found to be predictive of survival. The poor prognosis of sarcomatoid MPM was independent of the extent of surgery, unlike other cell types (Ann. Thorac. Surg. 2010;89:907-11), and the combination of several immunohistochemical markers was found to be the only valid prognostic indicator of survival, including type of surgery.

source: european journal of cardio thoiracic surgery