Association for Academic Surgery
Impact of mesothelioma histologic subtype on outcomes in the Surveillance, Epidemiology, and End Results database

https://doi.org/10.1016/j.jss.2015.01.043Get rights and content

Abstract

Background

This study was conducted to determine how malignant pleural mesothelioma (MPM) histology was associated with the use of surgery and survival.

Methods

Overall survival of patients with stage I–III epithelioid, sarcomatoid, and biphasic MPM in the Surveillance, Epidemiology, and End Results database from 2004–2010 was evaluated using multivariate Cox proportional hazards models.

Results

Of 1183 patients who met inclusion criteria, histologic subtype was epithelioid in 811 patients (69%), biphasic in 148 patients (12%), and sarcomatoid in 224 patients (19%). Median survival was 14 mo in the epithelioid group, 10 mo in the biphasic group, and 4 mo in the sarcomatoid group (P < 0.01). Cancer-directed surgery was used more often in patients with epithelioid (37%, 299/811) and biphasic (44%, 65/148) histologies as compared with patients with sarcomatoid histology (26%, 58/224; P < 0.01). Among patients who underwent surgery, median survival was 19 mo in the epithelioid group, 12 mo in the biphasic group, and 4 mo in the sarcomatoid group (P < 0.01). In multivariate analysis, surgery was associated with improved survival in the epithelioid group (hazard ratio [HR] 0.72; P < 0.01) but not in biphasic (HR 0.73; P = 0.19) or sarcomatoid (HR 0.79; P = 0.18) groups.

Conclusions

Cancer-directed surgery is associated with significantly improved survival for MPM patients with epithelioid histology, but patients with sarcomatoid and biphasic histologies have poor prognoses that may not be favored by operative treatment. The specific histology should be identified before treatment, so that surgery can be offered to patients with epithelioid histology, as these patients are most likely to benefit.

Introduction

Malignant pleural mesothelioma (MPM) is a rare but aggressive and often fatal malignancy [1]. Most patients present with advanced disease, and the median overall survival is approximately 1 y [1]. The recommended treatment for mesothelioma is dependent on both stage and histology. Previous studies have found epithelioid MPM to portend a better prognosis than sarcomatoid or biphasic histologic subtypes [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12]. Therefore, it is recommended that patients with medically operable clinical stage I–III epithelioid or mixed histology disease undergo multimodality therapy including surgery [1]. Current National Comprehensive Cancer Network (NCCN) guidelines [13] recommend chemotherapy alone for all patients who have sarcomatoid histology, as well as for medically inoperable or clinical stage IV patients.

Despite these guidelines, the relative benefit of surgery for mesothelioma compared with nonsurgical therapy has not been well quantified, and different opinions exist with regards to benefit of surgery when applied alone or in conjunction with chemotherapy [14], [15], [16], [17]. Furthermore, there is a lack of data to establish the relative efficacy of extrapleural pneumonectomy (EPP) compared with pleurectomy and decortication (P/D), leading to further controversy [15], [18], [19], [20], [21], [22]. A randomized feasibility study did not find that EPP improved outcomes compared with chemotherapy alone for patients with mesothelioma [23], [24], [25]. In addition, several studies have shown that a small but significant number of patients with nonepithelioid MPM undergo surgery as the initial cancer-directed therapy [2], [8], [10], [11], [14]. This study was undertaken to improve the level of evidence available to clinicians who are considering offering surgery to patients with mesothelioma using a population-based database to better quantify the survival benefits of surgery. Specifically, the purpose of this study was to assess outcomes of patients who did or did not receive cancer-directed surgery for epithelioid, sarcomatoid, and biphasic subtypes of MPM stratified by stage using population-based data from the United States National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program database that has captured a geographically diverse cohort of patients diagnosed with MPM.

Section snippets

Methods

We reviewed the SEER database from 2004–2010 for patients with stage I–III MPM by International Classification of Diseases for Oncology, 3rd Edition morphology codes 9050–9053 and 9055. Cases before 2004 were not included for analysis because specific American Joint Committee on Cancer's TNM staging (sixth edition) [26] information was not recorded in the SEER database until 2004. Only patients whose histologic subtype was known were included in the study. For this study, we used the more

Results

Of 4935 patients with MPM identified in the SEER database between 2004 and 2010, 1183 patients met study criteria (Fig. 1). The majority of patients were white, male, and aged ≥70 y, with a right-sided disease (Table 1). A total of 69% of patients had epithelioid histology (n = 811), whereas 19% had sarcomatoid histology (n = 244) and 12% had biphasic histology (n = 148).

A total of 422 patients received cancer-directed surgery (36%). Percentage of patients receiving surgery during the study

Discussion

MPM is an aggressive tumor associated with poor outcomes, yet the best treatment options remain controversial, in particular with regards to the role of surgery in treatment of this disease. In this population-based study, surgery was associated with improved survival in the epithelioid group but not in biphasic or sarcomatoid groups. Specifically, median survival for patients with epithelioid subtype MPM was 19 mo with surgery and 14 mo for patients who did not undergo surgery (P < 0.01). For

Conclusions

In summary, cancer-directed surgery is associated with improved survival for MPM patients with epithelioid histology. Although operative treatment is recommended for patients with biphasic histology per NCCN guidelines [1], surgery was not associated with improved survival in this cohort of patients. As expected, outcomes of patients with sarcomatoid histology were not improved by operative treatment. Although guidelines do not recommend surgery for sarcomatoid patients, over 25% of patients

Acknowledgment

This work was supported by the NIH funded Cardiothoracic Surgery Trials Network (M.G.H. and M.F.B.), 5U01HL088952-05, Medical Scientist Training Program NSRA T32GM007171 (R.R.M.), and the American College of Surgeons Resident Research Scholarship (C.-F.J.Y.). The authors thank Roberto Sanchez Lagunes Jr and Shannon Adams for their assistance on this project.

Authors' contributions: R.R.M. and C.J.Y. contributed equally to this work in study design, data analysis and interpretation, writing, and

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