An extrapleural pneumonectomy (EPP) is one of the major surgical options available for patients with mesothelioma. It is a radical surgery and is characterized by the complete resection of the affected lung and pleura, as well the removal of parts of the diaphragm and pericardium. Due to the extent of the surgery involved, it has long been associated with high mortality and high morbidity figures, but modern techniques have greatly reduced the incidences of these complications, especially the mortality figures. An EPP is often the only way of achieving what many mesothelioma doctors feel is the most important endpoint of surgery: macroscopically complete resection (MCR)–where all signs of visible tumor tissue have been removed from the patient. For people who are diagnosed in the mid-to-late stages of pleural mesothelioma—which is the majority of presentations—an EPP is generally their best option to prolong life.

However, even as the procedure has become more efficient and less prone to complications, there are still a number of people who will experience serious side effects from it. Because of this, an active community of mesothelioma researchers are trying to identify the clinical conditions that are most likely to have a role in the development of complications. A team of researchers from Ontario, Canada have recently added to this literature on risk factors with an analysis of their experience performing extrapleural pneumonectomies for patients with malignant pleural mesothelioma.

Overview of the Study

The authors undertook a retrospective analysis of the surgical results of all 62 patients with mesothelioma who underwent an EPP at the Toronto General Hospital between 1993 and 2007. The average age of the patient was 58 years-old, with more men than women represented in the sample population. The majority of patients presented with left-side malignancy and epithelial subtype, respectively, and the most common disease stage at time of procedure was Stage III.

In their analysis of the risk factors involved with the procedure, the authors grouped individual complications into thematic composites and focused their analysis around the following questions: induction chemotherapy-yes or no, greater or less than 60 years of age, male vs. female, early stage vs. late stage, side of surgery and greater or less than 4 units of red blood cell (RBC) transfusions during surgery. They also looked at the overall incidences of complications vs. those who did not suffer any complications at all.

Results

Of the 62 patients enrolled, 22 (35%) suffered a major complication and 4(6.5%) died postoperatively (defined within the study as death within 30 days of surgery or during the same hospital stay). Each of the four patients who died presented with a right-side malignancy, so the adjusted mortality factor was 14% for right-side presentation (4 of 28) and 0% for left-side presentation. In fact, with 54% of the patients experiencing some form of major complication, surgery for a right-side malignancy was statistically much more likely to have a post-operative complication than was surgery for a left-side malignancy, where only 21% of patients experienced serious side effects. Another statistically significant factor in the development of complications was advanced age, with patients older than 60 more likely to suffer a major side effect than were those younger 56.

One of the major questions the authors were interested in answering was what—if any—factor induction chemotherapy had on one’s risk for developing complications. Previous studies had suggested such a link, but had not definitively answered the question either way. Of the 62 patients who were studied in this cohort, 44 underwent induction chemotherapy with cisplatin before EPP. Pemetrexed or vinorelbine were the other main agents administered, although a few patients instead received gemcitabine or adriamycin. The authors found that these patients were much more likely to have lower hemoglobin levels than were patients who didn’t undergo chemotherapy, and, therefore, were more likely to require more RBC transfusions during surgery. For all patients, the median units of RBC transfusion were 4, while the median units for induction chemotherapy patients were 5.8. The authors concluded that induction chemotherapy itself was not a risk factor for complication, but requiring greater than 4 units of RBC was a major factor.

In terms of overall survival, the patient cohort demonstrated a three-year figure of 27% and a five-year figure of 23%. There was not a statistically significant difference in these survival figures between right and left EPP at 23% and 30% (even if the right EPP was more likely to lead to a postoperative complication), although there was significant difference between patients who received more than four blood transfusions and those who did not, with the former group having a three-year figure of 14% and the latter 36%.

Conclusion

An EPP is a necessary procedure for many patients with pleural mesothelioma. Therefore, learning more about the conditions most likely to cause serious side effects is a deeply important research program. While the complication rate of the procedure is still high, the authors have confirmed the results of a number of other studies which showed that mortality can be well-controlled. In this study here, only four patients were considered to have died postoperatively. The authors generally ruled out stage and gender as major risk factors, as well as induction chemotherapy itself, but they did identify right-side EPP and RBC transfusions of greater than four units as major factors. The authors specifically noted that those who received at least five RBC units saw an eightfold increase in the odds of death following surgery. They state theirs is the first analysis of RBC transfusion units for EPP and call for much more study on its surgical effects. Assuming these results will be replicated by other researchers, this study represents an important advancement in our knowledge of extraplerual pneumonectomy and our treatment of mesothelioma patients. If surgeons continue to increase the effectiveness and tolerability of EPP, the lives of thousands of patients would be improved.

Labels: mesothelioma