Extrapleural pneumonectomy for malignant pleural mesothelioma: outcomes of treatment and prognostic factors

Our plain-English summary of Extrapleural pneumonectomy for malignant pleural mesothelioma: outcomes of treatment and prognostic factors, by T.D. Yan, M. Boyer, M.M. Tin, et al (The Journal of Thoracic and Cardiovascular Surgery, 2009).

The study

• Authors: T.D. Yan, M. Boyer, M.M. Tin, D. Wong, C. Kennedy, J. McLean, P.G. Bannon, B.C. McCaughan
• Journal: The Journal of Thoracic and Cardiovascular Surgery
• Published: 2009;138(3):619-24
• Cited by: 61 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: This study aimed to evaluate the perioperative and long-term outcomes associated with extrapleural pneumonectomy for patients with malignant pleural mesothelioma.

Methods: From October 1994 to April 2008, 70 patients were selected for extrapleural pneumonectomy. Univariate analysis was performed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis with entering and removing limits of P less than .10 and P greater than .05, respectively, was used. The prognostic factors included age, gender, side of disease, asbestos exposure, histology, positron emission tomography, date of surgery, neoadjuvant chemotherapy, completeness of cytoreduction, lymph node involvement, perioperative morbidity, adjuvant radiotherapy, and pemetrexed-based chemotherapy.

Results: The mean age of patients was 55 years (standard deviation = 10). Fifty-eight patients had epithelial tumors. Six patients received neoadjuvant chemotherapy, 28 patients received adjuvant radiotherapy, and 16 patients received postoperative pemetrexed-based chemotherapy. Forty-four patients had no lymph node involvement. The perioperative morbidity and mortality were 37% and 5.7%, respectively. Complications included hemothorax (n = 7), atrial fibrillation (n = 6), empyema (n = 4), bronchopulmonary fistula (n = 3), right-sided heart failure (n = 2), pneumonia (n = 1), constrictive pericarditis (n = 1), acute pulmonary edema (n = 1), small bowel herniation (n = 1), and disseminated intravascular coagulopathy (n = 1). The median survival was 20 months, with a 3-year survival of 30%. Asbestos exposure, negative lymph node involvement, and receipt of adjuvant radiation or postoperative pemetrexed-based chemotherapy were associated with improved survival on both univariate and multivariate analyses.

Conclusion: The present study supports the use of extrapleural pneumonectomy-based multimodal therapy in carefully selected patients with malignant pleural mesothelioma.

In plain English

This study looked back at 70 patients with malignant pleural mesothelioma who had extrapleural pneumonectomy at the Royal Prince Alfred Hospital in Sydney, Australia, between October 1994 and April 2008. This operation removes the lung, pleura, diaphragm and pericardium on one side in one piece. These 70 were 16% of 424 mesothelioma patients treated by the same surgical team. Twenty-six patients (37%) had one or more complications around the time of surgery, and four (5.7%) died perioperatively. Median survival was 20 months. Thirty percent were alive at 3 years and 15% at 5 years. Forty-eight patients (69%) reported prior asbestos exposure; the article did not describe fiber types or jobs. Four factors were each associated with longer survival in both univariate and multivariate analyses: prior asbestos exposure, no lymph node involvement, radiotherapy after surgery, and pemetrexed-based chemotherapy after surgery. The authors concluded that the results support this surgery in carefully selected patients. They noted that the data were not randomized, so selection bias, unknown confounders and changes in care over time may explain the better survival seen with added treatments.

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: Observational cohort study of surgical patients, using data recorded in a prospective electronic database at one hospital
• Who was studied: 70 patients with malignant pleural mesothelioma selected for extrapleural pneumonectomy, out of 424 patients with a tissue diagnosis of the disease treated by one thoracic surgical team at the Royal Prince Alfred Hospital, Sydney, Australia, between October 1994 and April 2008. Mean age was 55 years, and 55 patients (79%) were male. 58 patients (83%) had epithelial tumors and 12 (17%) had biphasic or sarcomatoid tumors.
• Exposure: The study examined surgical treatment (extrapleural pneumonectomy), with or without chemotherapy or radiotherapy. Prior asbestos exposure, as reported by patients, was one of 13 factors tested for links with survival. 48 patients (69%) reported prior asbestos exposure. No fiber types, products, jobs or doses were described.
• Main results:
  • Twenty-six of the 70 patients (37%) had one or more perioperative complications. The most common were hemothorax (7), atrial fibrillation (6) and empyema (4).
  • Four of the 70 patients (5.7%) died perioperatively, each from a different cause.
  • For all 70 patients, median survival was 20 months (range 0 to 104 months). Survival was 62% at 1 year, 41% at 2 years, 30% at 3 years and 15% at 5 years. Twenty-six patients (37%) were alive at last follow-up.
  • Prior asbestos exposure was associated with improved overall survival on univariate analysis (P = .002) and multivariate analysis (P = .021). In Table 1, median survival was 28 months for patients with prior exposure versus 12 months for those without, and 3-year survival was 43% versus 10%.
  • Absence of lymph node involvement was associated with improved survival on univariate analysis (P = .020) and multivariate analysis (P = .033). In Table 1, median survival was 24 months with no lymph node involvement (44 patients), 19 months with 1 lymph node station involved (19 patients), and 7 months with more than 1 station involved (7 patients).
  • Adjuvant radiotherapy was associated with improved survival on univariate analysis (P = .001) and multivariate analysis (P = .047). In Table 1, median survival was 90 months for the 28 patients who had radiotherapy versus 14 months for the 42 who did not.
  • Postoperative pemetrexed combined with cisplatin or carboplatin was associated with improved survival on univariate analysis (P = .010) and multivariate analysis (P = .019). In Table 1, median survival was 60 months for the 16 patients who received it versus 14 months for the 54 who did not.
  • Nine factors were not statistically significant predictors of overall survival in this series: age, gender, side of disease, tumor subtype (P = .069), PET scan (P = .062), date of surgery, neoadjuvant chemotherapy, complete macroscopic cytoreduction and perioperative morbidity.
  • In subgroup analysis, patients with skip lymph node metastases (N2 nodes involved but N1 nodes spared) had better survival than patients in other N2 categories (median 21 vs 7 months, P = .015). Their survival was not significantly different from that of patients with N1 disease (P = .468).
• The authors' conclusion: The authors concluded that the results support the use of extrapleural pneumonectomy in carefully selected patients with malignant pleural mesothelioma. They called the information on adjuvant therapy preliminary and said it should be explored in prospective clinical trials.
• Limitations the authors state:
  • The data were nonrandomized, so unknown confounders may have influenced the outcome.
  • Selection bias and timing may account for the apparent improved survival with adjuvant radiotherapy and combination chemotherapy. Adjuvant therapy was used only after 2002, when surgical technique or case selection may also have improved.
  • Lead-time bias may explain better survival compared with historic controls, because patients may have had surgery earlier in the course of their disease.
  • When interrelated factors are entered together into a multivariate analysis, the true significance of each factor is difficult to assess.
  • The skip-metastasis finding rests on small numbers and on subjective lymph node evaluation by different pathologists, and some patients may have been staged inaccurately.
  • The small number of patients with sarcomatoid and biphasic tumors may partly explain why no survival difference by tumor subtype was found.

Topics

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

Medical terms in this study, explained in our Lexicon: Extrapleural Pneumonectomy (EPP), Pleural Mesothelioma, Multivariate Analysis, Asbestos Exposure, Histology, Neoadjuvant Chemotherapy, Cytoreductive Surgery, Pemetrexed (Alimta).

Related studies

• Summary of prognostic factors and patient selection for extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma — C. Cao, T.D. Yan, et al. (2011)
• PI3K/mTOR signaling in mesothelioma patients treated with induction chemotherapy followed by extrapleural pneumonectomy — B.K. Bitanihirwe, M. Meerang, et al. (2014)
• Staging of patients after extrapleural pneumonectomy for malignant pleural mesothelioma--institutional review and current update — C. Cao, S.K. Krog Andvik, et al. (2011)
• Low calretinin expression and high neutrophil-to-lymphocyte ratio are poor prognostic factors in patients with malignant mesothelioma undergoing extrapleural pneumonectomy — S.C. Kao, S. Klebe, et al. (2011)
• Hemithoracic radiation therapy after extrapleural pneumonectomy for malignant pleural mesothelioma: Toxicity and outcomes at an Australian institution — A. Bece, M.M. Tin, et al. (2015)
• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)

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