Survival by Histologic Subtype of Malignant Pleural Mesothelioma and the Impact of Surgical Resection on Overall Survival

Our plain-English summary of Survival by Histologic Subtype of Malignant Pleural Mesothelioma and the Impact of Surgical Resection on Overall Survival, by V. Verma, C.A. Ahern, C.G. Berlind, et al (Clinical Lung Cancer, 2018).

The study

• Authors: V. Verma, C.A. Ahern, C.G. Berlind, W.D. Lindsay, J. Shabason, S. Sharma, M.J. Culligan, S. Grover, J.S. Friedberg, C.B. Simone
• Journal: Clinical Lung Cancer
• Published: 2018;19(6):e901-e912
• Cited by: 48 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: For the 3 histologic subtypes of malignant pleural mesothelioma (MPM)-epithelioid, sarcomatoid, and biphasic-the magnitude of benefit with surgical management remains underdefined.

Materials And Methods: The National Cancer Data Base was queried for newly diagnosed nonmetastatic MPM with known histology. Patients in each histologic group were dichotomized into those receiving gross macroscopic resection versus lack thereof/no surgery. Kaplan-Meier analysis evaluated overall survival (OS) between cohorts; multivariable Cox proportional hazards modeling assessed factors associated with OS. After propensity matching, survival was evaluated for each histologic subtype with and without surgery.

Results: Overall, 4207 patients (68% epithelioid, 18% sarcomatoid, 13% biphasic) met the study criteria. Before propensity matching, patients with epithelioid disease experienced the highest median OS (14.4 months), followed by biphasic (9.5 months) and sarcomatoid (5.3 months) disease; this also persisted after propensity matching (P < .001). After propensity matching, surgery was associated with significantly improved OS for epithelioid (20.9 vs. 14.7 months, P < .001) and biphasic (14.5 vs. 8.8 months, P = .013) but not sarcomatoid (11.2 vs. 6.5 months, P = .140) disease. On multivariable analysis, factors predictive of poorer OS included advanced age, male gender, uninsured status, urban residence, treatment at community centers, and T4/N2 disease (all P < .05). Chemotherapy and surgery were independently associated with improved OS, as was histology (all P < .001).

Conclusion: This large investigation evaluated surgical practice patterns and survival by histology for MPM and found that histology independently affects survival. Gross macroscopic resection is associated with significantly increased survival in epithelioid and biphasic, but not sarcomatoid, disease. However, the decision to perform surgery should continue to be individualized in light of available randomized data.

Copyright © 2018 Elsevier Inc. All rights reserved.

In plain English

This was a retrospective study using the U.S. National Cancer Database. It covered patients diagnosed from 2004 to 2012 with malignant pleural mesothelioma that had not spread to distant sites and whose tissue type was known. Of 4,207 patients, 2,867 had epithelioid, 773 sarcomatoid and 567 biphasic tumors. The authors compared survival by tissue type, and between patients who did or did not have gross macroscopic resection (extrapleural pneumonectomy or extended pleurectomy/decortication). Before matching, median survival was 14.4 months (95% confidence interval 13.6-14.9) for epithelioid, 9.5 months (8.7-10.3) for biphasic and 5.3 months (4.7-5.9) for sarcomatoid disease. After patients were matched on other characteristics, surgery was associated with longer median survival for epithelioid (20.9 vs 14.7 months) and biphasic disease (14.5 vs 8.8 months). For sarcomatoid disease (11.2 vs 6.5 months) the difference was not statistically significant. The authors called the data hypothesis-generating and concluded that surgery decisions should stay individualized in light of randomized trial data. They noted that a database study cannot fully control for selection bias and lacked data on surgical complications and quality of life.

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 analysis of a national cancer registry database (National Cancer Database), with Kaplan-Meier survival analysis, multivariable Cox regression and propensity score matching
• Who was studied: 4,207 patients in the U.S. National Cancer Database diagnosed 2004-2012 with newly diagnosed malignant pleural mesothelioma of known histology. Patients with distant metastasis (M1) and palliative-care patients were excluded. There were 2,867 (68%) epithelioid, 773 (18%) sarcomatoid and 567 (13%) biphasic cases. The database draws only on Commission on Cancer-accredited facilities.
• Exposure: Not an asbestos exposure study. The factors studied were tumor histologic subtype and receipt of gross macroscopic resection (extrapleural pneumonectomy or extended pleurectomy/decortication), compared with non-definitive surgery or no surgery.
• Main results:
  • Before matching, median overall survival was 14.4 months (95% CI 13.6-14.9) for epithelioid, 9.5 months (95% CI 8.7-10.3) for biphasic and 5.3 months (95% CI 4.7-5.9) for sarcomatoid disease.
  • After propensity matching, the survival differences by histology persisted: median 16.5 months for epithelioid, 11.0 for biphasic and 7.6 for sarcomatoid disease (p less than 0.001).
  • Before matching, surgery was associated with longer median survival in all three types: epithelioid 20.9 vs 12.7 months, sarcomatoid 8.0 vs 4.9 months, biphasic 12.9 vs 7.9 months (all p less than 0.001).
  • In propensity-matched patients, gross macroscopic resection was associated with higher median survival in epithelioid (20.9 vs 14.7 months, p less than 0.001) and biphasic (14.5 vs 8.8 months, p=0.013) disease. The difference in sarcomatoid disease (11.2 vs 6.5 months, p=0.140) was not statistically significant.
  • In the multivariable model of the pre-matched cohort, biphasic (HR 1.79, 95% CI 1.47-2.18) and sarcomatoid (HR 2.01, 95% CI 1.62-2.50) histology were independently associated with higher mortality compared with epithelioid. Chemotherapy and surgery were associated with improved survival.
  • Factors independently associated with poorer survival were advanced age, male gender, urban residence, uninsured status, treatment at a community center, higher comorbidity index, and T4 or N2 disease.
  • In node-positive patients, surgery was associated with improved survival for epithelioid and biphasic disease. It was not associated with improved survival for sarcomatoid disease (7.1 vs 5.6 months, p=0.420), where sample sizes were low.
• The authors' conclusion: The authors concluded that histology was independently associated with overall survival. They found that surgery, although underutilized, was associated with improved survival in epithelioid and biphasic but not sarcomatoid patients. They called the data hypothesis-generating and said surgery decisions should remain individualized in light of randomized data.
• Limitations the authors state:
  • As a retrospective database study, it cannot fully control for selection biases in who received treatment.
  • There was no information on surgical complications or quality of life.
  • The findings depend on the database's histology coding. The database does not record the proportion of sarcomatoid component in biphasic tumors, or whether histology came from a biopsy or a surgical specimen.
  • Grouping non-definitive surgery with no surgery is inherently biased in terms of confounding factors.
  • Only accredited facilities contribute data, so the findings may not represent the whole U.S. population.
  • Immortal time bias and lead-time bias cannot be fully controlled.
  • The database lacks variables such as pulmonary function tests and salvage therapies. It also lacks endpoints such as cancer-specific survival.
  • The nodal subgroup analysis should be interpreted cautiously because of selection bias and small sample sizes, particularly for sarcomatoid and node-positive patients.

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: Histological Subtype, Pleural Mesothelioma, Surgical Resection, Overall Survival, Epithelioid, Sarcomatoid, Biphasic Mesothelioma, Histology.

Related studies

• Treatment of malignant pleural mesothelioma with chemotherapy preceding versus after surgical resection — V. Verma, C.A. Ahern, et al. (2019)
• Accuracy of pleural biopsy for the diagnosis of histologic subtype of malignant pleural mesothelioma: Necropsy-based study of 134 cases — P.G. Barbieri, D. Consonni, et al. (2022)
• CRS/HIPEC with Major Organ Resection in Peritoneal Mesothelioma Does not Impact Major Complications or Overall Survival: A Retrospective Cohort Study of the US HIPEC Collaborative — D. Roife, B.D. Powers, et al. (2020)
• Impact of Detecting Occult Pathologic Nodal Disease During Resection for Malignant Pleural Mesothelioma — V. Verma, R.E. Wegner, et al. (2020)
• Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection — D.J. Sugarbaker, R.R. Gill, et al. (2013)
• Therapeutic outcome according to histologic subtype in 121 patients with malignant pleural mesothelioma — G.L. Ceresoli, L.D. Locati, et al. (2001)

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