Challenging a dogma; AJCC 8th staging system is not sufficient to predict outcomes of patients with malignant pleural mesothelioma

Our plain-English summary of Challenging a dogma; AJCC 8th staging system is not sufficient to predict outcomes of patients with malignant pleural mesothelioma, by O. Abdel-Rahman (Lung Cancer, 2017).

The study

• Author: O. Abdel-Rahman
• Journal: Lung Cancer
• Published: 2017;113:128-133
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: The 8th edition of malignant pleural mesothelioma (MPM) American Joint Committee on Cancer (AJCC) staging system has been published. The current analysis aims to evaluate its performance in a population-based setting among patients recorded within the surveillance, epidemiology and end results (SEER) database.

Methods: SEER database (2004-2013) has been accessed through SEER*Stat program and AJCC 8th edition stage groups were reconstructed. Survival analyses (overall and cancer-specific) were conducted according to 6th and 8th editions through Kaplan-Meier analysis. Cox-regression multivariate model was also utilized for pair wise comparisons between different prognostic groups for overall and cancer-specific survival.

Results: A total of 5382 patients with MPM were identified in the period from 2004 to 2013. According to the 6th edition, significant pair wise P values for overall survival included: IA vs. III (P=0.027); IA vs. IV: P<0.0001; IB vs. IV: P<0.0001; II vs. III: P<0.0001; II vs. IV: P<0.0001; III vs. IV: P<0.0001). According to the 8th edition, significant pair wise P values for overall survival included: all stages vs. IV: P<0.0001; IA vs. II: P=0.046; IA vs. IIIA: P=0.022; IA vs. IIIB: P <0.0001; IB vs. II: P<0.0001; IB vs. IIIB: P<0.0001; II vs. IIIA: P<0.0001; IIIA vs. IIIB: P<0.0001). C-index for 6th edition was 0.539 (SE: 0.008; 95% CI: 0.524-0.555); while C-index for 8th edition was 0.540 (SE: 0.008; 95% CI: 0.525-0.556). Based on the above findings, a simplified staging system was proposed and overall and cancer-specific survivals were evaluated according to the simplified system. For overall and cancer-specific survival assessment, P values for all pair wise comparisons among different stages were significant (<0.01).

Conclusion: The prognostic performance of both the 6th and 8th AJCC editions is unsatisfactory; there is a need for a more practical and prognostically relevant staging system for MPM.

Copyright © 2017 Elsevier B.V. All rights reserved.

In plain English

This study used the SEER cancer registry to test how well the AJCC 6th and 8th edition staging systems predicted survival in malignant pleural mesothelioma. It did not study asbestos exposure. It covered 5382 patients diagnosed from 2004 to 2013. The C-index, a measure of how well a system separates patients by survival, was 0.539 (95% CI 0.524 to 0.555) for the 6th edition and 0.540 (95% CI 0.525 to 0.556) for the 8th. Stage IIIA patients (8th edition, only 200) seemed to do better than those in earlier stages. The author then proposed a simpler three-group system: low, intermediate and high disease burden. All comparisons between its groups were statistically significant. After adjustment, compared with the low-burden group, the high-burden group's hazard ratio was 1.515 (95% CI 1.408 to 1.630) for death from any cause and 1.574 (95% CI 1.442 to 1.718) for death from mesothelioma. The author concluded both AJCC editions performed unsatisfactorily and a more practical staging system is needed. The author noted missing chemotherapy and performance status data, and that most patients were staged clinically.

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 population-based analysis of a cancer registry database (SEER), comparing staging systems with survival analyses (Kaplan-Meier, log-rank and adjusted Cox regression)
• Who was studied: 5382 patients with malignant pleural mesothelioma recorded in the SEER-18 registry, diagnosed 2004 to 2013; 79.1% male, 62.5% older than 70 years, 77.7% staged clinically
• Exposure: No asbestos or other exposure was studied. The study compared cancer staging systems: AJCC 6th edition, AJCC 8th edition, and a proposed simplified system.
• Main results:
  • In all patients, the C-index was 0.539 (SE 0.008; 95% CI 0.524 to 0.555) for the 6th edition and 0.540 (SE 0.008; 95% CI 0.525 to 0.556) for the 8th edition
  • The author described a modest improvement in prognostic performance for the 8th edition compared with older AJCC editions
  • Patients in 8th edition stage IIIA (200 patients) seemed to have a better prognosis than patients in earlier stages
  • Among patients without metastases, separation by stage was similarly poor whether staging was clinical or pathological, and whether histology was epithelioid or sarcomatoid
  • For the proposed simplified system (low burden: 8th edition stages IA, IB and II; intermediate: IIIA and IIIB; high: IV), all pairwise comparisons for overall and cancer-specific survival were significant (P less than 0.01). This held for epithelioid but not sarcomatoid histology.
  • In the adjusted model for overall survival (death from any cause), the high-burden group had a hazard ratio of 1.515 (95% CI 1.408 to 1.630) compared with the low-burden group
  • In the adjusted model for cancer-specific survival (death from mesothelioma), the high-burden group had a hazard ratio of 1.574 (95% CI 1.442 to 1.718) compared with the low-burden group
  • In the adjusted model for overall survival, the intermediate-burden group had a hazard ratio of 1.191 (95% CI 1.106 to 1.283) compared with the low-burden group
  • At the study cutoff, 3171 of 5382 patients (58.9%) had died of mesothelioma
• The authors' conclusion: The author concluded that the prognostic performance of both the 6th and 8th AJCC editions is unsatisfactory and that a more practical and prognostically relevant staging system for malignant pleural mesothelioma is needed
• Limitations the authors state:
  • SEER did not record systemic therapy or patients' functional status
  • There were no details of the type of surgery among patients treated with surgery
  • Precise tumor size information was missing for most patients (77%)
  • There was no information about molecular prognostic markers
  • Most patients were staged clinically from imaging rather than surgically, unlike the IASLC surgical database, and clinical and pathological staging correlate only modestly
  • Stage IIIA had a small sample size, which may have hindered assessment of its outcomes
  • Practicality remains an issue even with the proposed simplified system

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: AJCC, Staging, Pleural Mesothelioma, Epidemiology, SEER, Overall Survival.

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• A proposed new international TNM staging system for malignant pleural mesothelioma from the International Mesothelioma Interest Group — V.W. Rusch (1996)
• Evaluation of the clinical TNM staging system for malignant pleural mesothelioma: an assessment in 88 patients — L. Tammilehto, L. Kivisaari, et al. (1995)
• Supplementary prognostic variables for pleural mesothelioma: a report from the IASLC staging committee — H.I. Pass, D. Giroux, et al. (2014)
• MiR-score: a novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma — M.B. Kirschner, Y.Y. Cheng, et al. (2015)
• Peritoneal mesothelioma proposal for a staging system — G. Sebbag, P.H. Sugarbaker (2001)

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