Introduction: Trimodality therapy (TMT), consisting of extrapleural pneumonectomy (EPP), preoperative or postoperative combination chemotherapy, and high-dose hemithoracic radiotherapy, is the only therapy reported to achieve long-term survival in selected patients with malignant pleural mesothelioma (MPM). Thus, TMT was introduced as an option for such patients in Western Australia in 2004. However, TMT has never been compared with non-TMT therapy in the same patient population, thereby introducing a potential for selection bias.
Method: We performed a retrospective review of all patients referred for TMT consisting of EPP, adjuvant chemotherapy, and hemithoracic radiotherapy at a quaternary referral institution. Patient eligibility for referral for TMT was based on patients' tolerability for pneumonectomy, epithelioid subtype, and computed tomography and positron emission tomography scanning indicating operable disease, with the exclusion of extrapleural lymphadenopathy and metastatic disease (clinical stage T1-3N0-1M0). Eligible patients consenting to TMT also underwent a surgical staging procedure (bilateral thoracoscopy, mediastinoscopy, and laparoscopy) to confirm eligibility before EPP.
Results: Thirty-six patients have been referred for TMT since 2004, and there has been a median of 27 months follow-up; of 31 patients having surgical staging, eight were ineligible for EPP and one declined EPP. Of the 22 planned for EPP, 18 underwent EPP and four had unresectable disease at surgery. There was one death in hospital six days post-EPP and another death postdischarge and 28 days post-EPP (30-day mortality 11%); 15 of 16 EPP survivors received adjuvant chemotherapy and 14 completed adjuvant radiotherapy. Pathologic analysis of the 18 resected EPP specimens revealed N2 disease in seven patients (39%) and nonepithelioid subtype in six patients (33%). Local recurrence did not occur among EPP survivors; however, 56% (9 of 16 patients) developed distant recurrence. Median and 1-year survival did not differ between the 18 EPP patients and 18 non-EPP patients (20.4 versus 20.7 months and 76 versus 78%, respectively; p = NS).
Discussion: In this case series, we could not demonstrate a survival benefit for patients in the EPP group compared with that in the non-EPP group. After surgical staging, 26% of patients were ineligible for TMT. Thus, surgical staging is essential before proceeding with EPP. Despite aggressive imaging and surgical staging, 39% of patients will have N2 disease and 18% will have unresectable disease at operation. Although complete locoregional control was achieved with TMT, distant recurrence affected most EPP survivors despite careful patient selection and a high rate of completion of adjuvant therapy. We conclude that TMT for operable epithelioid MPM requires further assessment in randomized controlled trials.