9 Original Article Page 1 of 9 The role of extrapleural pneumonectomy for malignant pleural mesothelioma: reviewing 20-years of experience Raphael S. Werner, Olivia Lauk, Isabelle Opitz Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland Contributions: (I) Conception and design: All authors; (II) Administrative support: RS Werner, O Lauk; (III) Provision of study materials or patients: All authors; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Isabelle Opitz, MD, FEBTS. Department of Thoracic Surgery, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland. Email: [email protected]. Background: For patients with malignant pleural mesothelioma (MPM), a multimodality treatment concept including neoadjuvant chemotherapy and radical surgery offers improved overall survival. While the lung-sparing extended pleurectomy and decortication (EPD) has become the preferential surgical approach, the more aggressive extrapleural pneumonectomy (EPP) remains reserved for a selected group of patients. Based on our experience from the past two decades, we aim to discuss and assess today’s role of EPP. Methods: Out of 523 MPM patients intended to be treated by induction chemotherapy followed by macroscopic complete resection between January 1999 and December 2019, we identified 151 consecutive patients who underwent EPP at our center. All patients were treated within a multimodality concept including neoadjuvant chemotherapy with platinum-based agents plus gemcitabine or pemetrexed. Clinical data were collected in an online database and analyzed retrospectively. Results: Of all patients, 57.6% were of IMIG stage IA or IB (n=87), 39.0% of all patients IMIG stage IIIA or IIIB (n=59). Mean tumor volume after induction chemotherapy was 294.6±315.0 cm3. Most patients were operated in the first decade between 1999 and 2009 [112 patients (74.2%)]. The overall 30- and 90-day mortality was 4.6% and 10.6%, respectively. The median overall survival was 18.5 months. Major postoperative morbidity was assessed as a composite outcome and occurred in 38.4% of all patients. Conclusions: Although EPD became the procedure of first choice, EPP is a reasonable approach in selected patients with high tumor burden and extensive involvement of the lung parenchyma, where parenchyma-sparing resection is technically not feasible or functionally not rational. All patients should be preoperatively assessed and informed about the eventuality of EPP, depending on intraoperative findings. Keywords: Extrapleural pneumonectomy (EPP); malignant pleural mesothelioma (MPM); surgical treatment; multimodality treatment; macroscopic complete resection Received: 06 April 2020; Accepted: 14 May 2020; Published: 10 October 2020. doi: 10.21037/shc-20-64 View this article at: http://dx.doi.org/10.21037/shc-20-64 Introduction problem in third world countries in the next decades (1). In an adequately selected group of patients with resectable Malignant pleural mesothelioma (MPM) is a very aggressive malignancy with a poor prognosis, requiring disease, a multimodality approach including neoadjuvant a complex treatment. Despite the fact that asbestos, the chemotherapy with platinum and anti-folate doublet, main etiologic factor, has been banned in most industrial followed by surgical resection is part of the most recent countries for several decades, its global incidence is still guidelines (2-5). Due to the tumor’s anatomical restraint increasing and MPM is expected to become a significant with proximity to the heart and the big vessels, the chest © Shanghai Chest. All rights reserved. Shanghai Chest 2020;4:40 | http://dx.doi.org/10.21037/shc-20-64 Page 2 of 9 Shanghai Chest, 2020 wall and the diaphragm, extensive resection is often not Hospital Zurich between January 1999 and December possible and microscopic tumor will eventually be left 2019, we identified 151 patients who underwent EPP. In behind. The aim of a radical surgical treatment is therefore all patients included in this study, the diagnosis of MPM to achieve macroscopic complete resection (MCR) (4,6). had been histopathologically confirmed and a clinical T1–3 MCR can be obtained by both extrapleural pneumonectomy N0–2 M0 stage was present. A predicted postoperative (EPP) or extended pleurectomy and decortication (EPD). forced expiratory volume in 1 second (FEV1) >1 L or >40% While EPP includes an en-bloc resection of the parietal based on the preoperative spirometry was required for EPP. pleura, the lung, the pericardium and the ipsilateral Perfusion was assessed routinely by ventilation/perfusion diaphragm, EPD forms a lung-sparing approach where (V/Q) scan. In all cases, surgery was performed within a only parietal and visceral pleura, the pericardium and the multimodality approach following three or four cycles of ipsilateral diaphragm are resected. An isolated pleurectomy neoadjuvant chemotherapy with platinum-based agents and and decortication (PD) can be evaluated in selected gemcitabine or pemetrexed. The combination of cisplatin patients with no macroscopic or histological signs of tumor and pemetrexed was used as a standard after improved infiltration into the pericardium or diaphragm. survival rates had been shown in a randomized phase III trial While EPP had already been established for treatment in 2003 (16). In order to identify patients who will benefit refractory tuberculosis in 1949 (7), EPP for MPM was only from a multimodality approach, a multimodality prognostic introduced in a series of 29 patients by Butchart et al. in score (MMPS) was established at our institution and has 1976 (8). While in these patients, in-hospital mortality was been shown to serve as an independent prognosticator as high as 31%, the safety of this procedure significantly for overall survival (OS) (17). In patients with an MMPS improved over the following decades with short-term of 3 or 4 after neoadjuvant chemotherapy, the OS is not mortality ranging between 2.2% and 8.0% in recent prolonged by subsequent radical surgery. The MMPS was reports (3,9-12). The technique of EPP has been described therefore routinely assessed before surgical resection since in previous articles and is largely consistent, including its establishment in 2015. An approval of the local ethics an extended lateral thoracotomy, extrapleural dissection committee was obtained for the retrospective analysis of the of the tumor, as well as resection and reconstruction mesothelioma data base (StV 29-2009, EK-ZH 2012-0094). of the pericardium and the diaphragm (10). Increasing evidence from a number of retrospective cohort studies Study endpoints has demonstrated similar overall survival in EPP and EPD. Since EPP has been shown to be associated with a We aimed to assess perioperative mortality (in-hospital higher short-term mortality and morbidity, most centers mortality, 30-day mortality, 90-day mortality), postoperative have established EPD as a standard of care (3,12-14). The major morbidity and OS in our patient cohort. Major spared lung parenchyma and ideally preserved functional morbidity was defined as a composite outcome combining reserve after EPD results in improved quality of life and postoperative hemorrhage requiring surgery, a failure of the better tolerance towards further treatment (15). However, diaphragmatic or pericardial patch and/or diaphragmatic also in EPD the management of prolonged air leak and hernia, chylothorax, pleural empyema, bronchopleural postoperative infections of the pleural cavity remain a fistula (BPF), acute respiratory distress syndrome (ARDS) challenge. and pulmonary embolism. For baseline characteristics of In this present article we aim to assess and discuss today’s our cohort we collected data on gender, age, body mass role of EPP after induction chemotherapy followed by index (BMI), preoperative lung function [FEV1, forced MCR, based on our own 20-year experience. We present the vital capacity exhaled (FVCex), diffusion capacity of carbon following article in accordance with the STROBE reporting monoxide (DLCO)], smoking status, exposure to asbestos, checklist (available at http://dx.doi.org/10.21037/shc-20-64). MPM histology, the MMPS and neoadjuvant chemotherapy. The response to induction chemotherapy was evaluated by the modified response evaluation criteria in solid tumors Methods (RECIST) and assessed using a dedicated reading workstation Out of 523 patients with the diagnosis of MPM who (Impax 5.2, AGFA, Bonn, Germany). The PET-CT scans underwent surgical resection within a multimodality concept before and after chemotherapy were linked at the identical at the Department of Thoracic Surgery of the University anatomical position and tumor thickness was measured © Shanghai Chest. All rights reserved. Shanghai Chest 2020;4:40 | http://dx.doi.org/10.21037/shc-20-64 Shanghai Chest, 2020 Page 3 of 9 at three different levels in two distinct positions (18). variables. Missing data (as well as loss to follow-up) was MPM staging data are based on the TNM 8th edition [2016]. addressed by available case analysis. The 1-, 2-, and 3-year Mean tumor volume pre and post chemotherapy were survival rates, as well as median OS were assessed by assessed based on the staging positron emission computed Kaplan-Meier curves. Statistical analysis was performed in tomography (PET-CT). During the reported 20 years, the IBM SPSS