Predictors of long-term survival following radical surgery for malignant pleural mesothelioma

Our plain-English summary of Predictors of long-term survival following radical surgery for malignant pleural mesothelioma, by A. Nakas, D. Waller (European Journal of Cardio-thoracic Surgery, 2014).

The study

• Authors: A. Nakas, D. Waller
• Journal: European Journal of Cardio-thoracic Surgery
• Published: 2014;46(3):380-5; discussion 385
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: The aim of radical surgery for malignant pleural mesothelioma (MPM) is to achieve greater survival than from chemotherapy alone. Although adverse overall prognostic factors have already been determined, our aim was to identify the most important factors affecting long-term survival arbitrarily defined as >24 months.

Methods: We retrospectively reviewed the records of 252 patients (35 females; 193 epithelioid and 59 biphasic; 112 extrapleural pneumonectomy (EPP); 140 extended pleurectomy decortication (EPD)) who survived for at least 90 postoperative days. We tested for factors affecting overall cancer-related mortality and specific clinical factors predicting the 24-month survival.

Results: The overall median survival was 18.2 (SE 1.3, 95% CI 15.8-20.7 months). There was no difference in survival between EPP and EPD (P = 0.92). One hundred and twenty-eight patients received induction, adjuvant or palliative chemotherapy. Seventy-seven (30.6%) patients survived for >24 months. On univariate analysis, age at operation over 60 years (P = 0.044), pT4 stage (P = 0.041), any lymph node metastases (P = 0.002), biphasic cell type (P = 0.00) and no administration of chemotherapy (P = 0.00) were associated with decreased survival. On multivariate analysis, age <60 (P = 0.018, OR = 0.7), epithelioid disease (P = 0.001, OR = 0.56) and negative nodes (P = 0.009, OR = 0.67) were associated with increased survival and no administration of chemotherapy (P = 0.00, OR = 1.9) with decreased survival. Factors predicting survival over 24 months included: age at operation under 60 (P = 0.014), epithelioid histology (P ≤ 0.00), negative nodes (P = 0.002) and chemotherapy (P = 0.022).

Conclusions: These results support a policy of accurate preoperative tissue diagnosis, nodal staging and induction chemotherapy prior to radical surgery for MPM, which can result in long-term survival. Trials investigating the role of surgery should be focused on confirming and refining these selection criteria.

© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

In plain English

This study looked back at 252 patients who had radical surgery for malignant pleural mesothelioma at Glenfield Hospital, Leicester, UK, in 2000–2012 and survived over 90 days afterwards. Sarcomatoid tumours were excluded. 193 had epithelioid and 59 biphasic disease; 112 had extrapleural pneumonectomy and 140 extended pleurectomy decortication. Asbestos exposure was not examined. Median survival from diagnosis was 18.2 months (95% CI 15.8–20.7), and 77 patients (30%) lived more than 2 years. Survival did not differ between the two operations (19.2 vs 16.2 months, P = 0.92) or between men and women. On multivariate analysis, age under 60, epithelioid cell type and cancer-free lymph nodes were associated with longer survival, and not receiving chemotherapy with shorter survival. The chemotherapy group combined treatment before surgery, soon after surgery and later palliative treatment. Median survival was 22.1 months (95% CI 19.1–25.1) for 128 patients given chemotherapy and 12.4 months (95% CI 7.7–14.9) for 102 not given it. The authors concluded the results support accurate tissue diagnosis, lymph node staging and chemotherapy before radical surgery. They noted the study was retrospective and limited to patients fit for surgery.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective review of patients drawn from a prospective departmental mesothelioma database (single surgical centre)
• Who was studied: 252 consecutive patients at Glenfield Hospital, Leicester, UK, who had radical surgery for epithelioid or biphasic malignant pleural mesothelioma over 12 years (2000–2012) and survived more than 90 days after surgery. Sarcomatoid cases and deaths within 90 days were excluded. The group had 217 men and 35 women with a mean age of 59. Of these, 193 had epithelioid and 59 biphasic disease, 112 had extrapleural pneumonectomy and 140 had extended pleurectomy decortication.
• Exposure: Asbestos exposure was not studied. The factors tested for an effect on survival were age, gender, cell type, type of operation, pT stage, pN stage and chemotherapy.
• Main results:
  • Survival was measured from diagnosis of the disease, not from surgery.
  • Overall median survival for all 252 patients was 18.2 months (SE 1.3, 95% CI 15.8–20.7).
  • No survival difference was found between extrapleural pneumonectomy and extended pleurectomy decortication (median 19.2 vs 16.2 months, P = 0.92).
  • No survival difference was found between men and women (P = 0.99).
  • On univariate analysis, epithelioid histology (P = 0.00) and negative lymph nodes (P = 0.002) were associated with increased survival. Age under 60 (P = 0.044) and chemotherapy (P = 0.00) were also associated with increased survival.
  • When pT1, pT2 and pT3 were grouped together, patients with pT4 disease had decreased survival (P = 0.041). Grouping pT1–2 against pT3–4 showed no difference.
  • On multivariate (Cox regression) analysis, age under 60 was associated with increased survival (P = 0.018, OR 0.7, 95% CI 0.51–0.94).
  • On multivariate analysis, epithelioid histology was associated with increased survival (P = 0.001, OR 0.56, 95% CI 0.39–0.79).
  • On multivariate analysis, negative lymph nodes were associated with increased survival (P = 0.009, OR 0.67, 95% CI 0.49–0.9).
  • On multivariate analysis, not receiving chemotherapy was a negative predictor of survival (OR 1.9, 95% CI 1.39–2.54). The authors' discussion calls this figure a hazard ratio.
  • The chemotherapy group merged preoperative (induction), early postoperative (adjuvant) and late (palliative) chemotherapy. This group was compared with patients who received no chemotherapy.
  • Median survival was 22.1 months for the 128 patients who received chemotherapy and 12.4 months for the 102 who did not. Only 128 of the 230 patients with chemotherapy data received it.
  • The 95% CI for median survival in the chemotherapy group (n = 128) was 19.1–25.1 months.
  • The 95% CI for median survival in the no-chemotherapy group (n = 102) was 7.7–14.9 months.
  • 77 patients (30%) survived more than 2 years.
  • Compared with patients who survived less than 2 years, those surviving more than 2 years more often had these features: age under 60 (P = 0.014), epithelioid cell type (P = 0.001), negative nodes (P = 0.002) and receipt of chemotherapy (P = 0.022).
• The authors' conclusion: The authors concluded that the results support accurate preoperative tissue diagnosis, nodal staging and induction chemotherapy before radical surgery for malignant pleural mesothelioma, which can result in long-term survival. They also said that trials of surgery should focus on confirming and refining these selection criteria.
• Limitations the authors state:
  • The study was retrospective.
  • There was selection bias, because only patients fit for radical surgery were included.
  • Provision of chemotherapy varied widely.
  • The predictors identified depend on markers known only after the operation (pT and pN stage) and on chemotherapy.
  • The long-term survival seen might reflect the patients and the variable biology of the disease rather than the surgery. This could only be settled by a randomized trial.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Chemotherapy, Epithelioid, Biphasic Mesothelioma, Extrapleural Pneumonectomy (EPP), Median Survival, Palliative Care, Multivariate Analysis.

Related studies

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• Prognostic Score of Long-Term Survival After Surgery for Malignant Pleural Mesothelioma: A Multicenter Analysis — G. Leuzzi, F. Rea, et al. (2015)
• The new case for cervical mediastinoscopy in selection for radical surgery for malignant pleural mesothelioma — A. Nakas, D. Waller, et al. (2012)
• Treatment factors associated with long-term survival after cytoreductive surgery and regional chemotherapy for patients with malignant peritoneal mesothelioma — H.R. Alexander, D.L. Bartlett, et al. (2013)
• Long-term Survival and Propensity Score Matched Outcomes of Bilateral vs. Unilateral Diaphragm Interventions in Cytoreductive Surgery plus Intra-peritoneal Chemotherapy — B. Singh, G. Singh, et al. (2018)
• How does the timing of chemotherapy affect outcome following radical surgery for malignant pleural mesothelioma? — A.J. Sharkey, K.J. O'Byrne, et al. (2016)

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