Elsevier

Lung Cancer

Volume 71, Issue 1, January 2011, Pages 75-81
Lung Cancer

Survival after trimodality therapy for malignant pleural mesothelioma: Radical Pleurectomy, chemotherapy with Cisplatin/Pemetrexed and radiotherapy

https://doi.org/10.1016/j.lungcan.2009.08.019Get rights and content

Abstract

Introduction

The role of surgery in the management of malignant pleural mesothelioma (MPM) is controversial and there are no established guidelines. We describe the feasibility and long-term outcomes associated with Radical Pleurectomy (RP) as surgical therapy modality in a standardized trimodality therapy concept of MPM.

Methods

From November 2002 to October 2007, 35 out of 102 consecutive patients with MPM were enrolled in our prospective database. They underwent trimodality therapy, including RP followed by 4 cycles of chemotherapy with Cisplatin (75 mg/m2)/Pemetrexed (500 mg/m2) and radiotherapy 4–6 weeks after operation.

Results

Median age was 65 years. Nineteen patients were in advanced stages III and IV (54.3%). Tumor histology was epithelial in 27 patients (77.1%). Macroscopic complete resection could be achieved in 18 patients (51.4%). Surgical morbidity/mortality and trimodality treatment-related mortality were 20.0%, 2.9% and 5.8%, respectively. Thirty-three patients completed the trimodality therapy. Median follow-up was 21.7 months. Overall median survival was 30.0 months. One-, 2-, and 3-year-survival were 69%, 50% and 31%, respectively. Advanced stages III/IV (p = 0.06), macroscopic incomplete resections (p = 0.001), non-epithelial histology (p = 0.55) and nodal metastases (p = 0.19) were associated with poorer survival.

Conclusions

The trimodality therapy concept with RP demonstrates promising results in terms of long-term survival, morbidity and mortality. We propose that a surgical philosophy of limiting the procedure related morbidity while achieving comparable cytoreductive results allows patients to maintain physiological reserve to be eligible for multimodality treatment options in the long-term. The observed and theoretical benefits of this trimodality treatment approach warrant confirmation in larger RCT.

Introduction

Malignant pleural mesothelioma (MPM) is an aggressive and rapidly fatal malignancy of the pleura. Conservative therapy of MPM results in median survival of 7 months after diagnosis [1]. Generally known single-modality therapies alone show disappointing results. Trimodality therapy seems to be the best treatment for malignant pleural mesothelioma [2].

The role of surgical resection in the management of MPM is still controversial. The criteria used to select patients for either Extrapleural Pneumonectomy (EPP) or Pleurectomy/Decortication (P/D) are dependent not only on the cardio-pulmonary status of the patient, tumor stage and intraoperative findings but also reflect the surgeons’ philosophy. There are no established guidelines. Radical Pleurectomy (RP) competes against EPP as surgical therapy modality. Both EPP and RP are cytoreductive treatment options with the aim to remove all gross disease and to achieve macroscopic complete resection [2].

Originally P/D was a palliative option for controlling pleural effusion [3]. But lung-sparing surgery for MPM seems to be an alternative for patients unsuitable or unwilling to undergo EPP in a multimodality therapy concept [4]. In the era of multimodality therapy of MPM RP could have an important role as a surgical philosophy of limiting the procedure related morbidity and mortality and thus allowing patients to achieve maximal benefit from all aspects of a multimodality concept.

Most studies evaluating multimodality therapies for MPM are based on retrospective analyses and their interpretation is difficult because of inhomogeneous patient groups studied. The aim of our prospective study was to analyze the feasibility and describe the long-term outcomes of patients treated with RP as surgical therapy modality in a standardized trimodality therapy concept.

Section snippets

Study design

All consecutive patients with histological diagnosis of MPM were enrolled in our prospective database. All patients were evaluated for trimodality therapy, including surgery with RP followed by four cycles of systemic chemotherapy with Cisplatin (75 mg/m2) and Pemetrexed (500 mg/m2), as well as radiation therapy 4–6 weeks after operation. The primary outcome was survival. The secondary outcomes included morbidity and mortality. The local Ethics Board approved this study. All patients gave written

Patient's characteristics

From November 2002 to October 2007, 35 of 102 consecutive patients with histological diagnosis of MPM met the inclusion criteria and were prospectively enrolled in this study. Most of the excluded patients were treated previously for MPM or were not eligible for multimodality treatments. All 35 patients underwent thoracoscopic evaluation because of unilateral pleural effusion. The mean age was 65.0 ± 8.1 years (range 47–81 years). Twenty-nine patients were male (82.9%). Median pre-surgical forced

Discussion

In this pilot investigation of RP as surgical therapy modality in a standardized trimodality therapy concept including adjuvant Cisplatin/Pemetrexed and radiotherapy, we found promising results in terms of treatment-related morbidity and mortality and long-term survival. Combined with the fact that this less invasive surgical treatment approach was feasible in all stages of MPM this study adds new information regarding the role of surgery in the management of MPM.

EPP is the most aggressive

Conclusions

A trimodality therapy concept with RP as surgical strategy demonstrates promising results in terms of treatment-related morbidity and mortality and long-term survival. This multimodality approach is feasible in all stages of MPM. We propose that a surgical philosophy of limiting the procedure related morbidity while achieving comparable cytoreductive results allows patients to maintain physiological reserve to be eligible for multimodality treatment options in the long-term. We believe that RP

Conflict of interest statement

There is no potential conflict of interest to disclose.

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    Presented in part at the 16th European Conference on General Thoracic Surgery, Bologna, Italy, June 8–11, 2008, and at the European Multidisciplinary Conference in Thoracic Oncology, Lugano, Switzerland 1–3 May, 2009.

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