Dr. Cameron Comments on the U.K. Mesothelioma and Radical Surgery Trial (MARS)

LOS ANGELES.  This well-designed seminal study from Tom Treasure and his colleagues in England, while small, provides compelling and incontrovertible evidence that supports our long-held position at the Pacific Meso Center that the use of radical lung-removing surgery, ie., EPP, is completely unsupported by medical data. 

Tom Treasure compares the EPP to the barbaric and now nearly extinct practice of radical mastectomy for breast cancer.  We have been using the same analogy for years to drive the point home that surgery, if any, ought to be targeted and rational. This most recent trial is even more proof that no one suffering from the ravages of mesothelioma should be subjected to the further indignation of a radical, debilitating and useless operation based on "selected" data. 

Although this study definitively demonstrates that EPP should be placed into the realm of a historical archive of operations no longer performed, it does not address the potential benefit of lung-sparing approaches which have a much lower debilitating effect on patients. This approach remains a potentially viable option, particularly when combined with a "chronic disease" approach utilizing "maintenance" therapies to prevent disease regrowth following surgical removal.

December 7, 2010

--Robert Cameron, MD  
Director of the UCLA Mesothelioma Program

Principal results of the feasibility phase of the Mesothelioma and Radical Surgery trial (MARS-feasibility)

Tom Treasure 1,Judith Bliss 2,Carol Tan 3,James Entwisle 4,David Waller4,Mary O'Brien 5,Gill Coombes 2,Mark Webster-Smith 2,Lucy Kilburn2,Michael Snee 6,Gill Thomas 7,Liz Darlison 4,Loic Lang-Lazdunski8,Julian Peto 9
University College London, London, United Kingdom 1,The Institute of Cancer Research, Sutton, United Kingdom 2,St George's Hospital, London, United Kingdom 3,Glenfield Hospital, Leicester, United Kingdom 4,Royal Marsden NHS Foundation Trust, London, United Kingdom 5,St James's Hospital, Leeds, United Kingdom 6,Leicester Royal Infirmary, Leicester, United Kingdom 7,Guy's Hospital, London, United Kingdom 8,London School of Hygiene and Tropical Medicine, London, United Kingdom 9

Background

Extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) was reported over 30 years ago (Butchart et al. Thorax 1976;31(1)), but its effect on survival has never been tested in an RCT.  The MARS trial was designed to establish if EPP, as part of tri-modality treatment, offered any survival or quality of life (QoL) advantage. To determine feasibility and acceptability a feasibility study of 50 patients was instigated (MARS-feasibility).

Method

Patients with histologically confirmed resectable MPM were eligible. Registered patients had neoadjuvant chemotherapy followed by restaging.  Patients remaining eligible were randomised to EPP followed by radical radiotherapy or to No EPP.  Endpoints were the proportion of patients subsequently randomised, completion of allocated treatment; peri-operative mortality, survival and QoL (EORTC).

Results

Screening logs were received for 257 patients: 108/257 (42.0%) were approached for MARS-feasibility and 68/108 (63.0%) were registered.  44 patients were registered without screening logs, thus 112 were registered in total. Of these, 50/112 (44.6%) patients were randomised (EPP=24, No EPP=26) between 2006 and 2009.  16/24 (66.7%) EPP patients completed surgery; 8/24 (33.3%) remained fit enough to receive radical radiotherapy. Two No-EPP patients chose to receive EPP off study. 30 deaths had occurred at the time of analysis (EPP=17, No EPP=13).   Four were peri-operative deaths (EPP=3, No EPP=1).  12-month survival rates were EPP=52.2% (95%CI:30.5-70.0), No EPP=73.1% (95%CI:51.7-86.2). A Cox model for survival adjusted for gender, histological subtype, stage and age gave a hazard ratio of 2.75 (95%CI:1.21-6.26; p=0.02) in favour of No EPP.  Global QL was lower for EPP, with the nadir 6 weeks after randomisation.  Median QL score did not return to baseline levels.  

Conclusion

MARS-feasibility suggests that timely accrual to the larger study to assess efficacy of EPP would be unachievable without international collaboration.  Despite small numbers, MARS-feasibility provides no evidence that EPP is beneficial for these patients.

(see http://www.ncri.org.uk/ncriconference/2010abstracts/abstracts/LB74.htm)  

Note: This report should be regarded as preliminary as it ihas not yet fully peer reviewed but it is strongly against EPP and data on which that is based will not change. (Dec 5, 2010).