Extrapleural pneumonectomy (EPP) and pleurectomy/decortication (PD) are the two major surgical options for the treatment of pleural mesothelioma. An EPP is usually described as the complete resection of the pleura, the pericardium, the diaphragm and the entire lung on the affected side. With pleurectomy/decortication the lung is spared, but both the parietal and visceral pleurae are removed, as are the pericardium and the diaphragm if necessary. Both procedures are considered radical surgery, with EPP the more invasive of the two.

There is considerable controversy and debate in the mesothelioma community regarding which of the procedures is the most effective and what the conditions are that should govern the choice of the one over the other. Some previous studies have shown that patients who undergo PD are less likely to experience serious consequences and may have a longer post-surgery median survival, but the conclusions of these previous studies have often been questioned due to small sample size or an inability to directly compare the patient cohorts who completed the procedures.

In an attempt to settle this controversy, doctors from some of the country’s premier mesothelioma treatment centers have recently released the results of a study on the efficacy of EPP vs. PD in a large cohort of patients. The results of the individual treatments were analyzed on a number of different levels and the resulting analysis is the most complete yet offered about the relationship between EPP and PD and the conditions under which each procedure should be used.

Overview of the Study

The authors of the study undertook a retrospective analysis of 663 total patients who underwent an EPP (n=385) or a PD (n=278) between 1990 and 2006 at one of the following cancer centers: Memorial Sloan-Kettering Cancer Center, The National Cancer Institute or the Karmanos Cancer Institute. In looking at the historical records of these patients, their analysis compared not only the overall efficacy of the procedures themselves, but also the effect the various sub-groups had within the two major cohorts: histology, tumor staging, performance status, age, gender, etc., etc.

A number of important differences separate the present study from previous ones that also involved these procedures. In many of the prior studies, the surgical method was written-in to the study design itself and the actual procedure was only a part of the subsequent analysis. The procedures themselves were rarely compared directly and when they were other study factors would often limit the scope of the conclusions that could be drawn from the results. Another major difference between this study and previous ones was that the end points of earlier studies often looked only at time to progression, instead of overall survival, as the present study does. It is for these reasons, as well as others—such as the large sample size—that the authors describe this study as the largest, most comprehensive study yet completed on the use of extrapleural pneumonectomy versus pleurectomy/decortication.

As we said above, this study looked at 663 mesothelioma patients who underwent either EPP or PD during a sixteen-year period. Most patients were older males who presented with Stage II or Stage III disease characterized by the epitheloid histological subtype. However, there were important differences between the two groups. The patient cohort who underwent PD were on average older than the EPP group and more often presented with early stage disease, while the EPP group were more likely to receive some form of multimodal treatment and more often presented with epitheloid mesothelioma than did the PD group. The EPP group was also more likely to demonstrate more adverse post-surgical events than the PD was likely to.

When taken as an entire group, median survival was determined to be 14 months. However, this figure is truly an average and masks some very interesting findings. The over-all five year survival figure for the entire group was 12%. For patients who presented with Stage I disease, median survival rose dramatically to 38 months, while patients with stage II disease demonstrated a median survival of 19 months. Patients who were Stage III at time of presentation had a median survival of 11 months, while those with Stage IV disease averaged 7 months from diagnosis.

Other analyses that showed a significant impact on survivability were epithelial histological subtype, female gender and multi-modal therapy: all of which increased survival times.

A univariate analysis that compared PD to EPP showed that patients who underwent PD were associated with a significantly better median survival than did patients with EPP. However: this conclusion disappears when the analysis takes on a multi-variate methodology by considering the characteristics of the patient’s total presentation. When controlling for tumor stage, no significant differences were found between the PD group and the EPP group. The same is found when tumor stage is replaced by histology or gender. The differences that do exist between these cases are not significant enough to conclude that one procedure is somehow “better” or “more appropriate” than the other one is if presentation-specific elements are not accounted for. In fact, the authors specifically note the importance of taking the patient’s total presentation into account when deciding between the procedures.

In a discussion included at the end of article between the study’s lead author and peer reviewers of the study, Dr. Raja M. Flores, the lead author, and Dr. David Sugarbaker, Chief of the Division of Thoracic Surgery at Brigham and Women’s in Boston, discuss the importance of achieving macroscopic complete resection (MCR), i.e. removal of all visible tumor, to maximize the treatment’s efficacy. The choice of procedure will be made at the time of the thoracotomy, which is the procedure to open the chest cavity for surgery, and should be guided by the extent of tumor present. If the disease is caught in the early stages, P/D might suffice for MCR, but for advanced disease with significant spread and tumor bulk, an EPP is often the only procedure that could potentially achieve MCR, so that is the procedure that should be used.

Dr. Flores specifically states the two procedures are not interchangeable and they should not be seen that way.

Conclusion

The question of EPP vs. PD has long been a controversial debate among mesothelioma physicians. The authors of this study state that decisions on which procedure to use have more often been the result of surgeon bias rather than the application of sound science and one of their goals for the study was to help inform physicians on this question. In this, they have succeeded in providing valuable evidence regarding the efficacy and applicability of both extrapleural pneumonectomy and pleurectomy/decortication for the treatment of pleural mesothelioma. Neither procedure leads to statistically significant differences in overall survival, but each procedure is given a clear domain for use: PD for early stage disease and EPP for later stage disease or disease with a heavy tumor burden.

Even as they call for more studies comparing these two procedures, the authors have succeeded in making an important contribution to the controversy surrounding EPP vs. PD. However, neither procedure represents a truly curative approach to mesothelioma and the authors also call for more study and development of non-surgical treatments, as well as for more effective adjuvant therapy.

Labels: mesothelioma