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

Our plain-English summary of 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, by V.W. Rusch, K. Chansky, H.L. Kindler, et al (Journal of Thoracic Oncology, 2016).

The study

• Authors: V.W. Rusch, K. Chansky, H.L. Kindler, A.K. Nowak, H.I. Pass, D.C. Rice, L. Shemanski, F. Galateau-Sallé, B.C. McCaughan, T. Nakano, E. Ruffini, J.P. van Meerbeeck, M. Yoshimura, IASLC Staging and Prognostic Factors Committee, advisory boards, and participating institutions
• Journal: Journal of Thoracic Oncology
• Published: 2016;11(12):2112-2119
• Cited by: 150 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: The M component and TNM stage groupings for malignant pleural mesothelioma (MPM) have been empirical. The International Association for the Study of Lung Cancer developed a multinational database to propose evidence-based revisions for the eighth edition of the TNM classification of MPM.

Methods: Data from 29 centers were submitted either electronically or by transfer of existing institutional databases. The M component as it currently stands was validated by confirming sufficient discrimination (by Kaplan-Meier analysis) with respect to overall survival (OS) between the clinical M0 (cM0) and cM1 categories. Candidate stage groups were developed by using a recursive partitioning and amalgamation algorithm applied to all cM0 cases.

Results: Of 3519 submitted cases, 2414 were analyzable and 84 were cM1 cases. Median OS for cM1 cases was 9.7 months versus 13.4 months (p = 0.0013) for the locally advanced (T4 or N3) cM0 cases, supporting inclusion of only cM1 in the stage IV group. Exploratory analyses suggest a possible difference in OS for single- versus multiple-site cM1 cases. A recursive partitioning and amalgamation-generated survival tree on the OS outcomes restricted to cM0 cases with the newly proposed (eighth edition) T and N components indicates that optimal stage groupings for the eighth edition will be as follows: stage IA (T1N0), stage IB (T2-3N0), stage II (T1-2N1), stage IIIA (T3N1), stage IIIB (T1-3N2 or any T4), and stage IV (any M1).

Conclusions: This first evidence-based revision of the TNM classification for MPM leads to substantial changes in the T and N components and the stage groupings.

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

In plain English

This international, multi-institutional cohort study of malignant pleural mesothelioma tested whether the existing metastasis (M) categories separated patients by survival, and proposed revised stage groups for the eighth TNM edition. Data came from 29 centers on 4 continents, for diagnoses from January 1995 to June 30, 2013. Of 3,519 submitted cases, 2,414 were analyzable. The article did not examine asbestos exposure. Median overall survival was 9.7 months for the 84 patients with clinically staged distant spread (M1). It was 13.4 months for clinically staged T4 or N3 cases without distant spread (proposed stage IIIB); the hazard ratio comparing the groups was 1.64 (p = 0.0013). The authors said this supported placing only M1 in stage IV. Survival appeared better with only a single metastatic lesion. Using a statistical tree method, the authors proposed six stages, IA (T1N0) to IV (any M1). The authors concluded that this first evidence-based revision leads to substantial changes. Because M1 cases were few, analyses of metastatic sites and lesion numbers were exploratory; the authors called these findings hypothesis-generating. They noted that some stage differences were small or differed between clinical and pathological staging.

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, multi-institutional cohort study (analysis of the IASLC mesothelioma staging database); the existing M component was validated against survival, and revised stage groupings were proposed
• Who was studied: Patients with newly diagnosed, cytologically or histologically confirmed malignant pleural mesothelioma from 29 centers on 4 continents, diagnosed between January 1995 and June 30, 2013; 3,519 cases submitted, 2,414 analyzable, 84 with clinical M1 disease
• Exposure: Not studied. The article analyzes tumor stage (T, N and M categories) and survival. It does not report asbestos or fiber exposure.
• Main results:
  • Of 3,519 submitted cases, 2,414 were analyzable and 84 were clinical M1 cases
  • The existing M component was validated by confirming that survival differed sufficiently between the clinical M0 and M1 groups
  • Median overall survival was 9.7 months for clinical M1 cases, compared with 13.4 months for the proposed 8th edition stage IIIB (T4 or N3, M0); the hazard ratio of 1.64 (p = 0.0013) compares the M1 group with that stage IIIB group
  • The authors said the significant difference (HR 1.64, p = 0.0013) supported including only M1 cases in stage IV
  • In an exploratory analysis of M1 cases, prognosis appeared better when there was only a single metastatic lesion
  • Among T4 cases, survival did not differ statistically between those without and with lymph node involvement: 14.9 months for T4N0 versus 13.9 months for T4N+ (p = 0.94)
  • Under the 7th edition, stages IB and II had similar prognoses and were not significantly different
  • By best stage, proposed 8th edition stages IIIA and IIIB were similar in prognosis, with no separation before 12 months
  • Recommended 8th edition stage groupings: T1N0M0 stage IA; T2-3N0M0 stage IB; T1-2N1M0 stage II; T3N1M0 stage IIIA; T1-3N2M0 and T4 any N M0 stage IIIB; any T any N M1 stage IV
• The authors' conclusion: The authors concluded that this first evidence-based revision of the TNM classification for malignant pleural mesothelioma leads to substantial changes in the T and N components and the stage groupings.
• Limitations the authors state:
  • Analyses of metastasis sites and numbers of metastatic sites and lesions were limited to exploratory survival estimates because there were few M1 cases
  • The authors described the M1 findings on single versus multiple metastases as hypothesis-generating
  • In some comparisons, survival differences between stages were small, or were significant for clinical but not pathological stage (or the reverse)
  • More data, including more patients treated non-surgically, are needed to confirm the results
  • Future data may lead to expansion or consolidation of the proposed stage groupings

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, Mesothelioma Staging, M Descriptor, Stage Grouping, TNM Classification, Mesothelioma, Pleural Mesothelioma, Lung Cancer.

Related studies

• The IASLC Mesothelioma Staging Project: Proposals for Revisions of the N Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma — D. Rice, 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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