Is it Time to Consider Pleurectomy and Decortication as the Only Surgical Treatment for Malignant Pleural Mesothelioma?
Authors: Michael J. Weyant
Journal: Journal of Thoracic Oncology (2012)

Radical extrapleural pneumonectomy (EPP), and pleurectomy and decortication (P/D) have emerged as the two main surgical treatments of malignant pleural mesothelioma (MPM). Until recently, EPP has been considered the gold standard operation with P/D being performed if the patient's physical status or preference dictated it. The operative mortality of EPP is reported to be as high as 18% in some series that has generated interest in studying the P/D procedure more intensively because of lesser complications and possibly better survival rates reported. Flores et al.1Flores RM Pass HI Seshan VE et al.Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients.J Thorac Cardiovasc Surg. 2008; 135: 620-626Abstract Full Text Full Text PDF PubMed Scopus (471) Google Scholar reported on a series of 663 patients who underwent either EPP or P/D as part of their treatment for MPM . This is the largest series to date examining the outcomes of P/D as a modality of treatment for MPM. Their results demonstrate that there may be circumstances, such as in stage-I disease where an R0 resection is attained, in which P/D is a superior, less-morbid therapy. Likewise there may be a benefit to EPP in patients who have more extensive disease (stage II). This data suggests that the main therapeutic utility of any surgical therapy for MPM is in the possibility of attaining a complete macroscopic resection.1Flores RM Pass HI Seshan VE et al.Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients.J Thorac Cardiovasc Surg. 2008; 135: 620-626Abstract Full Text Full Text PDF PubMed Scopus (471) Google Scholar, 2Flores RM Surgical options in malignant pleural mesothelioma: extrapleural pneumonectomy or pleurectomy/decortication.Semin Thorac Cardiovasc Surg. 2009; 21: 149-153Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar The Mesothelioma and Radical Surgery (MARS) trial recently published the results of a trial randomizing 50 patients to the best therapy possible with or without EPP.3Treasure T Lang-Lazdunski L Waller D MARS trialists et al.Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study.Lancet Oncol. 2011; 12: 763-772Abstract Full Text Full Text PDF PubMed Scopus (527) Google Scholar The findings concluded by the authors suggest that because of the high morbidity of EPP it should be abandoned in the setting of trimodal therapy. The study was met with criticism on several grounds, namely the excessively high surgical mortality rate and the small sample size prohibiting significant power analysis.4Rusch VW The Mars trial: resolution of the surgical controversies in mesothelioma?.J Thorac Oncol. 2009; 4: 1189-1191Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar,5Weder W Stahel RA Baas P et al.The MARS feasibility trial: conclusions not supported by data.Lancet Oncol. 2011; 12: 1093-1094Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar Given these recently published studies it is no wonder that there is currently a significant amount of controversy surrounding treatment recommendations for MPM. The current study by Lang-Lazdunski et al.6Lang-Lazdunski L Bille A Belcher E et al.Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine followed by adjuvant chemotherapy in patients with malignant pleural mesothelioma.J Thorac Oncol. 2011; 6: 1746-1752Crossref PubMed Scopus (37) Google Scholar analyzes their significant experience in using both EPP and P/D to treat MPM. The study has the advantage of a single surgeon at a single institution performing all of the procedures as well as a large number of procedures over a relatively short (7-year) period. The reported surgical mortality is excellent at 4.5% for EPP and nil for the P/D group. The authors wisely point out that the technique of P/D is not standard everywhere. Two aspects of the P/D arm are unusual in the present study compared with those in studies at other centers, namely the hyperthermic providone/iodine lavage and the prophylactic low-dose radiation treatment postoperatively. The authors state that in all of the parameters evaluated patients undergoing P/D have a significantly improved survival rate. This includes stratification by preoperative stage and histology. The authors' conclusion that further studies randomizing patients with MPM should use P/D as the standard surgical procedure aligns with the suggestion from the MARS trial that EPP be abandoned. The study has several flaws that the authors recognized as well but the leap in transition of treatment away from EPP or any surgical therapy in the treatment of MPM should be made more cautiously. Although the authors do list the global reasons stating why a patient may be excluded from EPP they do not analyze further the real trends in the decision making regarding the decision to pursue EPP versus P/D. For example, it would be helpful to know if the main reasons were related to physical status or patient preference. In addition, even though the demographic features are consistent with the two groups there has to be a more common reason why patients are steered toward P/D. If it is because of performance status or lung function, illustrating this data would only strengthen the argument for P/D as these patients would have survived longer than their more healthy functional counterparts undergoing EPP. In addition, the conclusion that patients survive longer on a stage-for-stage basis is unfounded given the extremely small sample size once the study groups are broken down into stage designations. The results of these prior studies that suggest there is a stage difference in the outcome of treatment speaks to the biology of the disease. Flores et al.1Flores RM Pass HI Seshan VE et al.Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients.J Thorac Cardiovasc Surg. 2008; 135: 620-626Abstract Full Text Full Text PDF PubMed Scopus (471) Google Scholar suggest that there may be a benefit to performing different procedures for different stages of the disease. This makes sense given that the progression of disease from a pleural disease with no lung invasion (T1) to a disease where the only physical way to remove all macroscopic tumor is to perform some kind of lung resection (T2 and T3) suggests that different methods of local control may play a role at each stage of the disease. Both this trial and the MARS trial suffer from the fact that this notion is not recognized. It is helpful to examine the results of both this trial and the MARS trial concurrently as they both illustrate the difficulty in studying and providing recommendations for relatively rare diseases. MPM is not a heterogeneous disease, and as in other cancers it may not be wise to apply blanket statements recommending the treatment of the disease in any particular manner. In conclusion, the results of the current study by Lang-Lazdunski et al. provide additional data that should lead us to consider P/D in all trials of treatment for MPM. It is too early based on this data to completely abandon EPP altogether as there may be patient subsets where the potential reward outweighs the risk of the procedure.