The IASLC Mesothelioma Staging Project: Proposals for Revisions of the N Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma

Our plain-English summary of The IASLC Mesothelioma Staging Project: Proposals for Revisions of the N Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma, by D. Rice, K. Chansky, A. Nowak, et al (Journal of Thoracic Oncology, 2016).

The study

• Authors: D. Rice, K. Chansky, A. Nowak, H. Pass, H. Kindler, L. Shemanski, I. Opitz, S. Call, S. Hasegawa, K. Kernstine, C. Atinkaya, F. Rea, P. Nafteux, V.W. Rusch, Mesothelioma Domain of the IASLC Staging and Prognostic Factors Committee, advisory boards and participating institutions
• Journal: Journal of Thoracic Oncology
• Published: 2016;11(12):2100-2111
• Cited by: 100 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Nodal categories for malignant pleural mesothelioma are derived from the lung cancer staging system and have not been adequately validated. The International Association for the Study of Lung Cancer developed a multinational database to generate evidence-based recommendations to inform the eighth edition of the TNM classification of malignant pleural mesothelioma.

Methods: Data from 29 centers were entered prospectively (n = 1566) or by transfer of retrospective data (n = 1953). Survival according to the seventh edition N categories was evaluated using Kaplan-Meier survival curves and Cox proportional hazards regression analysis. Survival was measured from the date of diagnosis.

Results: There were 2432 analyzable cases: 1603 had clinical (c) staging, 1614 had pathologic (p) staging, and 785 had both. For clinically staged tumors there was no separation in Kaplan-Meier curves between cN0, cN1 or cN2 (cN1 versus cN0 hazard ratio [HR] = 1.06, p = 0.77 and cN2 versus cN1 HR = 1.04, p = 0.85). For pathologically staged tumors, patients with pN1 or pN2 tumors had worse survival than those with pN0 tumors (HR = 1.51, p < 0.0001) but no survival difference was noted between those with pN1 and pN2 tumors (HR = 0.99, p = 0.99). Patients with both pN1 and pN2 nodal involvement had poorer survival than those with pN2 tumors only (HR = 1.60, p = 0.007) or pN0 tumors (HR = 1.62, p < 0.0001).

Conclusions: A recommendation to collapse both clinical and pN1 and pN2 categories into a single N category comprising ipsilateral, intrathoracic nodal metastases (N1) will be made for the eighth edition staging system. Nodes previously categorized as N3 will be reclassified as N2.

Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

In plain English

This study used an international database built by the International Association for the Study of Lung Cancer. It examined how lymph node involvement relates to survival in malignant pleural mesothelioma, to inform the 8th edition of TNM staging. Of 3,519 cases submitted by 29 centers, 2,432 could be analyzed. The article does not discuss asbestos exposure. Among 1,322 clinically staged patients, median survival was 19 months for cN0, 17.6 months for cN1 and 16.2 months for cN2. cN1 did not differ significantly from cN0 or cN2. Among 851 patients with nodes checked at surgery, median survival was 24.0 months without node involvement, 16.9 months for pN1 and 17.4 months for pN2. pN1 and pN2 did not differ significantly. The 117 patients with both N1 and N2 involvement had worse survival than pN0 or N2-only patients. In 572 patients with both clinical and surgical staging, agreement was only slight (kappa 0.16, 95% CI 0.09 to 0.22). Node sampling was not standardized across centers. The authors recommended merging N1 and N2 into one N1 category and reclassifying N3 as N2.

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: International multicenter database analysis (survival analysis) of cases entered prospectively or transferred from retrospective records
• Who was studied: Patients with malignant pleural mesothelioma from 29 centers in Europe (48%), North America (33%), Asia (10%) and Australia (9%). Cases came from as early as 1995 but were mostly diagnosed between 2000 and 2013. Of 3,519 cases collected, 2,432 were analyzable: 1,603 with clinical staging, 1,614 with pathological staging and 785 with both. 1,322 patients were in the clinical N analysis and 851 in the pathological N analysis.
• Exposure: No asbestos or other exposure was studied. The factor analyzed was lymph node involvement, using the 7th edition TNM N categories (N0 to N3).
• Main results:
  • Clinically staged patients: median survival was 19 months for cN0, 17.6 months for cN1 and 16.2 months for cN2.
  • Clinically staged patients: survival for cN1 did not differ significantly from cN0 (HR = 1.15, p = .49) or from cN2 (HR = 1.06, p = .78).
  • Clinically staged patients: cN1 and cN2 combined, compared with cN0 after adjusting for region and sex, had median overall survival of 17.1 vs. 19.0 months (HR 1.18, p=.04).
  • Pathologically staged patients (851): median survival was 24.0 months for pN0, 16.9 months for pN1 (HR 1.51, p=0.006) and 17.4 months for pN2 (HR 1.56, p<0.001).
  • Pathologically staged patients: no significant survival difference was found between pN1 and pN2 (p=0.84). pN1 and pN2 combined had worse survival than pN0 (HR 1.55, p<0.0001).
  • Patients with both N1 and N2 metastases (n=117) had significantly worse survival than pN0 patients (HR 1.63, p<0.0001) and than pN2-only patients (HR 1.60, p=0.0007).
  • No significant survival difference was found between single-station and multistation pN1 or pN2 metastases (HR 1.11, p=0.44), or between pN2-only and pN1-only tumors (HR=0.83, p=0.28).
  • Among 572 patients with both clinical and pathologic N stage data, agreement between clinical and pathological staging was only slight (Kappa 0.16, 95% CI 0.09 to 0.22).
  • Exploratory analysis in 472 patients: the risk of nodal metastases was 14% with maximal tumor thickness less than 5.1 mm and 38% with thickness greater than 5.1 mm (p<0.0001).
• The authors' conclusion: The authors concluded that the current N1 and N2 categories were not associated with different survival. They recommended classifying any ipsilateral intrathoracic node metastasis as N1, and reclassifying ipsilateral supraclavicular or contralateral nodes (previously N3) as N2, in the 8th edition.
• Limitations the authors state:
  • The method and extent of nodal sampling during surgery were not standardized and varied across institutions.
  • N1 nodes may have been undersampled, so some N1 tumors may have been staged as N0.
  • Patient numbers were small for analyses by number of involved nodes, lymph node ratio and nodal distribution.
  • The tumor thickness findings were exploratory and need validation in larger numbers.
  • Few clinically staged patients had PET imaging or mediastinoscopy.
  • The 7 patients with pN3 disease were excluded from survival analyses because of small numbers.

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: IASLC, Staging, TNM Staging, Pleural Mesothelioma, Lung Cancer, Kaplan-Meier Curve, Hazard Ratio, Intrathoracic.

Related studies

• The IASLC Mesothelioma Staging Project: Proposals for the M Descriptors and for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Mesothelioma — V.W. Rusch, K. Chansky, et al. (2016)
• The IASLC Mesothelioma Staging Project: Improving Staging of a Rare Disease Through International Participation — H. Pass, D. Giroux, et al. (2016)
• Eighth Edition Staging of Thoracic Malignancies: Implications for the Reporting Pathologist — A.G. Nicholson, M.S. Tsao, et al. (2018)
• Poor Prognostic Factors in Patients with Malignant Pleural Mesothelioma Classified as Pathological Stage IB According to the Eighth Edition TNM Classification — T. Takuwa, M. Hashimoto, et al. (2018)
• Supplementary prognostic variables for pleural mesothelioma: a report from the IASLC staging committee — H.I. Pass, D. Giroux, et al. (2014)
• Peritoneal mesothelioma proposal for a staging system — G. Sebbag, P.H. Sugarbaker (2001)

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