Does radical surgery with or without radiotherapy improve the length and health-related quality of life in people with localised malignant mesothelioma, compared with chemotherapy and supportive care only?
Malignant pleural mesothelioma (that is, primary pleural cancer) is a difficult tumour to treat. Chemotherapy is usually given first to people who are fit enough to have it. It is not clear whether radical surgery and radiotherapy help people to live longer or improve their overall health-related quality of life.
We searched published medical articles to find research papers that looked at combined treatment strategies with surgery for treating people with primary pleural cancer. We looked for randomised clinical trials (where people were allocated at random to one of two or more treatments groups) and used information from those we found to form our conclusions. We found evidence up to 21 March 2017.
The review authors found two small randomised clinical trials, in which a total of 104 people with pleural mesothelioma were randomised. One trial compared the addition of surgery and radiotherapy to chemotherapy with chemotherapy alone. The other trial compared the addition of radiotherapy to chemotherapy and surgery with chemotherapy and surgery alone. These two small trials suggested that there is no added value for either radiotherapy or combined radiotherapy and surgery. We could not combine the data from the trials as we had intended, because the two trials were too different. We rated the quality of evidence as moderate for survival and low quality for all the other outcomes studied. The review authors identified three ongoing randomised clinical trials, the results of which have not been published yet.
Quality of evidence and conclusions
We only found two relevant trials. Both were small, which made the results uncertain. It is not clear whether giving a combination of surgery and radical radiotherapy after chemotherapy is better than giving chemotherapy alone. Radical radiotherapy does not seem to improve the results of surgery alone.
The overall strength of the evidence gathered in this review is low and there is a lack of available evidence to support the use of radical multimodality therapy in routine clinical practice (particularly as one trial suggests greater harm). Given the added cost of multimodality treatment and the possible increase in risk of adverse effects, the lack of evidence of their effectiveness probably means that these interventions should currently be limited to clinical trials alone.
Malignant pleural mesothelioma is an almost always fatal tumour, for which palliative platinum-based chemotherapy is currently the standard treatment. Multimodal therapeutic strategies incorporating surgery, radiation therapy or photodynamic therapy and chemotherapy have been recommended for selected patients but there is no consensus about their effectiveness.
To assess the benefits and harms of radical multimodal treatment options (including radical surgery ± radical radiotherapy ± photodynamic therapy ± systemic therapy) compared to each other or to palliative treatments, for people with malignant pleural mesothelioma.
We reviewed data from the Cochrane Lung Cancer group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase. We also checked reference lists of primary original studies, review articles and relevant conference proceedings manually for further related articles up to 21 March 2017.
We included parallel-group randomised controlled trials of multimodal therapy for people with malignant pleural mesothelioma (stages I, II or III) that measured at least one of the following endpoints: overall survival, health-related health-related quality of life, adverse events or progression-free survival. We considered studies regardless of language or publication status.
Two review authors independently extracted relevant information on participant characteristics, interventions, study outcomes, and data on the outcomes for this review, as well as information on the design and methodology of the studies. Two review authors assessed the risk of bias in the included trials using pre-defined 'Risk of bias' domains. We assessed the methodological quality using GRADE.
We conducted this review in accordance with the published Cochrane protocol. Two randomised clinical trials with 104 participants fulfilled our inclusion criteria. Both trials were at high risk of bias (for outcomes other than overall survival), and we rated the evidence as moderate quality for overall survival and low quality for all other outcomes. One trial compared combined extrapleural pneumonectomy (EPP) plus neoadjuvant platinum-based chemotherapy plus postoperative high-dose hemithoracic radiotherapy with combined EPP plus platinum-based chemotherapy. The other trial compared EPP plus postoperative hemithoracic radiotherapy with standard (non-radical) therapy alone following platinum-based chemotherapy (patients in the standard therapy arm received continued oncological management according to local policy, which could include further chemotherapy or palliative radiotherapy).
For the first trial, median overall survival calculated from registration was 20.8 months (95% confidence interval (CI) 14.4 to 27.8) in the no-radiotherapy group and 19.3 months (95% CI 11.5 to 21.8) in the radiotherapy group. For the second trial, median overall survival was 14.4 months (95% CI 5.3 to 18.7) for patients allocated to EPP and 19.5 months (95% CI 13.4 to time not yet reached) for patients randomised to standard non-radical therapy. In the second trial, 12 serious adverse events were reported during the study period: ten in the EPP group and two in the non-radical therapy group. Overall health-related quality of life scores were not different between the two arms in either study. We could not perform a meta-analysis of the two included trials due to clinical heterogeneity. We also identified three ongoing trials evaluating the topic of our review.