Extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma revisited: the Australian experience

A recent study by Yan et al. (2011) conducted at the Royal Prince Alfred Hospital in Sydney, Australia does more than look at the outcomes of the aforementioned treatment for malignant pleural mesothelioma.  This study, involving 540 patients, over 25 years also gives us a primer on the evolving treatment therapies for this condition.  As newer treatment therapies emerged, these therapies were given to eligible patients, starting with extrapleural pneumonectomy itself, in 1994 and extending to include both radiotherapy and chemotherapy. Chemotherapy consisted of a combination of pemtrexed, carboplatin and cisplatin.  While this alters the results significantly it also provides for an interesting introspective on the treatment of malignant pleural mesothelioma.

This study is noteworthy for both this reason, and as a study looking at a larger set of patients than many of the other studies on this topic.

Study Design: consecutive, non-randomized.

Patient population:  540 patients; organized into two groups for statistical analysis.  Group I – 270 patients (consecutive patients from March 1984 to September 1999.)  Group II – consecutive patients September 1999 to Jan 2008.  As the authors noted, due to the rarity of this condition in Australia, it took 25 years to recruit 540 patients for treatment.

Patient characteristics: the vast majority were male (455 patients)  with a mean age of 66 (+/- 11 years).  315 patients with right-sided disease, the remaining 225 with left-sided disease.

Disease subtypes:

235 patients with epithelial subtype, 212 with sarcomoid/ biphasic  (type determined by tissue pathology)

Treatments received:

69 patients had extrapleural pneumonectomy

269 patients received pleurectomy/ decortication

202 patients received pleurodesis

62 patients received post-operative radiotherapy starting 8 to 12 weeks after surgery. This treatment was added in 2002.

65 of the patients received adjunctive chemotherapy

Notably, as mentioned above, there was a distinct difference in the treatment allocation for groups I and II due to changing treatment protocols, and the development of new therapies.  While 22% of patients in group II received EPP, only 5% of patients in group I received the same surgical procedure.

Treatment strategies were also limited by patient factors; namely the patient’s physical condition / functional status as being considered able to withstand the proposed treatment therapy.  As mentioned in a previous post, extrapleural pneumonectomy is an extensive surgical procedure which requires significant patient reserves and pre-existing functional abilities for anticipated recovery.  In frail or debilitated patients, (as defined by criteria set forth by Yan et. al) EPP was not attempted.  Some of these patients received either pleurectomy with decortication.  In patients deemed too fragile to withstand either of these procedures, a talc pleurodesis (either by VATS or tube thoracostomy) was performed as a palliative procedure.  Unsurprisingly, the patients receiving palliative treatment options had shorter median survival periods.

Results:

18 patients died in the perioperative period, including 3 EPP patients.

Median follow-up period for the study was ten months.  At the time of follow-up the majority of patients (433 patients, 80%) had died with a median survival time of nine months for group I (range 0 – 115 months).

In group II, the median survival time was 13 months.  (range 0 – 72 months).

Long term survival by group:

Group   I                                                  Group II

1 year      35%                                                     50 %

2 year     16%                                                     22%

3 year       9 %                                                      12%

5 year        2 %                                                       9 %

These five-year survival rates highlight the importance of continued studies for the advancement of treatment therapies for this condition.

Factors associated with greater survival:

In reviewing their research, the authors were able to identify four independent factors that increased the likelihood of survival in this population. (See original article for discussion in further depth.)

1. Yan et. al found that the epithelial subtype was more favorable for patient survival, and that this subtype was more common in the patients in group II.

2.  The surgeon’s experience (of greater than 100 cases) was positively correlated with greater survival.  Surgeon expertise has been shown to be a factor for better patient outcomes in multiple procedures.

3. Patients who received EPP had improved survival compared to patients who received other treatments.  However, this also reflects a selection bias, since the patients who were eligible for EPP had better pre-operative functional status than patients who received other treatments.

4.  Premetrexed chemotherapy – patients who received this chemotherapy regimen had greater survival.

blog author’s note:

Despite dismal five year survival rates for treatment of malignant pleural mesothelioma by a multitude of treatment methods, extrapleural pneumonectomy (with adjuvant chemotherapy) appears to be the most effective cytoreductive surgery for this condition. ( As noted in related posts, HITHOC is an emerging therapy that combines the principles of both.) We will continue to follow research in these areas for the treatment of malignant pleural mesothelioma and invite the experts to add their comments.

Original article:   Yan, T. (2011). Improving survival rates after surgical management of malignant pleural mesothelioma: an australian institutional experience.  Ann Thorac Cardiovasc Surg 2011; 17: 243-249.  Primary author: Dr. Tristan Yan.