Why the MARS2 Trial Does Not Mean the End of All Mesothelioma Surgery

The published report of the MARS2 trial suggested that the addition of extended pleurectomy/decortication to chemotherapy for pleural mesothelioma was harmful. Thus, the report goes on, all disease should be considered as unresectable and no further mesothelioma surgery for survival benefit should be considered. This statement has changed clinical practice in the UK; however, the design of the MARS2 trial has several limitations which should prevent its conclusions being over interpreted. These limitations include the following: the inclusion of too many patients who would fall outside contemporary selection criteria including age, co-morbidity and histology; the unnecessary resection of too much tissue, particularly the diaphragm, and operating on patients too late in the disease process due to less than rigorous staging.

We retrospectively analysed the selection and outcome of data of 79 of the 158 (50%) patients who underwent surgery in the surgical arm of the MARS2 study who were operated by the authors in four of the five trial surgical centres. We revised the clinical staging of these patients by applying the criteria in the forthcoming 9th TNM edition including the measurement of pleural thickness.

Based on reported guidelines, the selection for surgery was reset as stage I or II epithelioid PM. We found that 52 (66%) of these patients (group A) would not have been considered for surgery using contemporary selection criteria for the following reasons: non-epithelioid PM in 5; cT/4 in 35; cT2N1 in 10 and 2 cT2N0 (pN1), which would have been detected on preoperative mediastinal biopsy. Of the 27 (34%) trial patients fulfilling current criteria (group B), 12 were cT1N0, 1 was cT1N1, 6 were cT1N0pN1 and 8 were cT2N0, all with epithelioid PM. The median survival of group B was 32 (1-72) months, which was significantly higher than in group A: 8.5 (1-55) months, p < 0.0005 (Mann-Whitney).

As contemporary selection criteria were not applied in MARS2, its conclusions cannot be universally applied to all those with PM. Together with the favourable postoperative survival in this selected group, we suggest that there is still scope for a further trial of surgery in early-stage epithelioid mesothelioma.