Written by Joyce Smith, BS. Study shows that extra-pleural pneumonectomy does not increase survival and quality of life for mesothelioma patients and may actually do more harm than good.
This study was done to evaluate the effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant mesotheliomas (1). Called the Mesothelioma and Radical Surgery (MARS) feasibility study, it compared the clinical outcomes of patients with confirmed mesothelioma who had been randomly assigned to undergo surgery or no surgery.
At the beginning of the study, a power calculation, on the basis of the difference claimed for effectiveness of EPP (1) and natural history data (2), suggested that 670 patients would be needed to identify any statistical differences between EPP and no EPP with overall survival as the primary outcome. Because of the anticipated difficulty in recruiting patients, the researchers did the following initial feasibility study with the objective of randomizing 50 patients within one year to EPP or no EPP to assess patient acceptability and to gauge the potential recruitment rate that could be expected in a larger trial. Randomization took longer than would be feasible to recruit sufficient numbers to a definitive trial (3).
Included in this multicenter, randomized, controlled study were patients 18 years or older who had confirmed mesothelioma and were considered well enough to undergo presurgical chemotherapy, surgery and post-operative radiotherapy commonly referred to as trimodal therapy (4). In the preregistration phase of this study all patients were required to undergo induction platinum –based chemotherapy followed by clinical review.
Between October 1, 2005 and November 3, 2008, 112 patients were registered (out of 246 patients screened). Of these, only 50 met the study criteria and were randomly assigned to receive extra pleural pneumonectomy (EPP) (n=24) or no extrapleural pneumonectomy (no EPP) (n=26). Patients were not selected for randomization mainly because of disease progression (33 patients), inoperability (5 patients), and patient choice (19 patients). For this analysis, all treatment data was included up to November 23, 2009 and outcome data to April 19, 2010.
Results on the survival and quality of life outcomes 2 years after recruitment was complete:
| Group | 12-month Progression-free Survival | Median Progression-free Survival | Median Survival |
|---|---|---|---|
| EPP | 34·8% (95% CI 16·6–53·7 | 7·6 months (5·0–13·4) | 14·4 months (5·3-18·7) |
| No EPP | 42·3% (23·5–60·0) | 9·0 months (7·2–14·7) | 19·5 months (13·4 months to time not yet reached) for the no EPP group. |
Note: The hazard ratio [HR] for overall survival in the EPP versus the no EPP group was 1·90 (95% CI 0·92–3·93; exact p=0·082) which is not statistically significant, and after adjustment for sex, histological subtype, stage, and age at randomization the HR was 2·75 (1·21–6·26; p=0·016).
Quality of Life Assessment Evaluation:
- Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires.
- Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses.
The authors concluded the following:
- There was no survival advantage for the EPP surgery group compared with the no EPP group.
- Patients allocated to the no EPP group had a better outcome than those allocated to EPP.
- The quality of life analyses reported “no significant differences between the two groups”
The authors found no evidence of benefit from EPP (within the trimodal therapy) over chemotherapy alone for survival or quality of life and felt that because of the high death rate associated with EPP in this trial and in other non-randomized studies, a larger study is not feasible. They concluded that the data gleaned from this study, even though limited, suggests that radical surgery in the form of EPP involving chemotherapy, surgery, and postop radiotherapy, provides no benefit to patients and in fact, might even harm them.
The authors added that, based on the MARS results, a further study is being developed that excludes EPP as the recommended surgery. They suggest that, when comparing EPP to a more recent surgical option called lung-sparing total pleurectomy and decortication with EPP, the latter may offer better patient survival.
Source: Treasure, Tom, Loic Lang-Lazdunski, David Waller, Judith M. Bliss, Carol Tan, James Entwisle, Michael Snee 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.” The lancet oncology 12, no. 8 (2011): 763-772.
Posted July 20, 2015.
Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.
References:
- Tan C, Swift S, Gilham C, et al. Survival in surgically diagnosed patients with malignant mesothelioma in current practice. Thorax 2002; 57iii: 36.
- Treasure T, Waller D, Tan C, et al. The Mesothelioma and Radical Surgery randomized controlled trial: the MARS feasibility study. J Thorac Oncol 2009; 4: 1254–58.
- British Thoracic Society; Society of Cardiothoracic Surgeons of Great Britain and Ireland Working Party. BTS guidelines: guidelines on the selection of patients with lung cancer for surgery. Thorax 2001; 56: 89–108.
