Multimodal Therapy of Epithelioid Pleural Mesothelioma

Improved Survival by Changing the Surgical Treatment Approach

Laura V. Klotz; Hans Hoffmann; Rajiv Shah; Florian Eichhorn; Christiane Gruenewald; Elena L. Bulut; Raffaella Griffo; Thomas Muley; Petros Christopoulos; Philip Baum; Peter Huber; Seyer Safi; Marc Kriegsmann; Michael Thomas; Helge Bischoff; Hauke Winter; Martin E. Eichhorn


Transl Lung Cancer Res. 2022;11(11):2230-2242. 

In This Article

Abstract and Introduction


Background: The exact role and type of surgery for malignant pleural mesothelioma (MPM) remains controversial. This study aimed at analyzing a 20-year single center perioperative experience in MPM surgery at our high-volume thoracic surgery center and comparing the overall survival after trimodal extrapleural pneumonectomy (EPP) and extended pleurectomy and decortication combined with hyperthermic intrathoracic chemoperfusion (EPD/HITOC) and adjuvant chemotherapy with that after chemotherapy (CTx) alone.

Methods: Patients with epithelioid MPM treated with neoadjuvant chemotherapy, EPP and adjuvant radiotherapy within a trimodal concept or EPD/HITOC in combination with adjuvant chemotherapy between 2001 and 2018 were included in this retrospective analysis. Surgical cohorts were compared to patients treated with standard chemotherapy.

Results: Overall, 182 patients (69 EPP, 57 EPD/HITOC, 56 CTx) were analyzed. Due to occupational exposure to asbestos for most of the patients, 154 patients (84.6%) were male. The patients in the surgical cohorts were significantly younger than those in the CTx cohort. There was no significant difference between the proportion of patient age and side. The median overall survival of the EPD/HITOC cohort with 38.1 months was significantly longer than that of the EPP and CTx cohorts (24.0 and 15.8 months). Better survival was significantly associated with an ECOG 0 performance status, age below 70 years, and negative lymph node status. In the multivariate analysis, EPD/HITOC was significantly associated with improved overall survival. Perioperative morbidity was lower in the EPD/HITOC group than in the EPP cohort.

Conclusions: EPD/HITOC is feasible and safe for localized epithelioid pleural mesothelioma. Changing the surgical approach to a less radical lung-sparing technique may improve overall survival compared to trimodal EPP.


Malignant pleural mesothelioma (MPM) is a rare and highly lethal cancer mainly associated with exposure to asbestos. Hereditary factors or radiotherapy might be responsible for development of MPM in some cases. Despite extensive research and current advances in systemic therapy, the prognosis is still very poor.[1,2] Because of the laminar tumor growth on visceral and parietal pleural tissue, oncologic complete surgical resection is not feasible. Consequently, multimodal treatment is the standard of care for early-stage MPM, with the aim of improving postoperative local tumor control.[3,4]

Since Sugarbaker and his team reported good outcomes after extrapleural pneumonectomy (EPP) in 1999, it has been performed in several high-volume thoracic surgery centers for early-stage MPM.[5,6] In the 2000s, there was great hope that tumor control could even be further improved by a maximal radical approach flanking surgery using neoadjuvant chemotherapy and adjuvant radiation therapy.[7] We performed trimodal EPP in our institution for MPM for more than a decade.[8] However, this was changed to lung-sparing surgery following increasing evidence of similar survival rates, lower perioperative morbidity, and improved quality of life.[9–11]

After an interim period between 2012 and 2013 in which both surgical concepts were performed, we completely changed our surgical approach. By the end of 2013, we performed only a combination of extended pleurectomy and decortication/hyperthermic intrathoracic chemoperfusion (EPD/HITOC), instead of trimodal EPP. Unlike the former trimodal concept with neoadjuvant chemotherapy followed by EPP and adjuvant radiotherapy, the new therapeutic concept is a combination of upfront cytoreductive surgery and HITOC, followed by four cycles of adjuvant cisplatin/pemetrexed chemotherapy.

The aim of this study was to analyze our 20-year single-institution experience of using multimodal treatment for patients with epithelioid MPM. We compared the period before and after the change of our surgical technique to the lung-sparing approach. Since there are only few studies comparing the results after surgical therapy with the survival of patients treated with palliative chemotherapy in the same institution, the outcomes of the two surgical treatment concepts were compared to the survival of patients treated with the standard of care, chemotherapy. We present this article in accordance with the STROBE reporting checklist (available at