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. 2025 Oct;20(10):1441-1458.
doi: 10.1016/j.jtho.2025.07.002. Epub 2025 Sep 8.

The International Association for the Study of Lung Cancer Staging Project: The Impact of Smoking Status on Lung Cancer Staging in the Ninth Edition of the TNM Classification

Lawson Eng  1 , William K Evans  2 , Megan Eisele  3 , Katherine K Nishimura  3 , Stephanie R Land  4 , Ramon Rami-Porta  5 , Carolyn M Dresler  6 , Hisao Asamura  7 , Joelle T Fathi  8 , Kendra Lechtenberg  9 , Valerie Rusch  10 , Mahdi Sheikh  11 , Murry W Wynes  9 , Keelan Zius  9 , Raymond U Osarogiagbon  12 , Graham W Warren  13 ; Members of the IASLC Staging and Prognostic Factors Group and of the Advisory Boards, and Participating Institutions and the IASLC Tobacco Control and Smoking Cessation Committee
Affiliations

The International Association for the Study of Lung Cancer Staging Project: The Impact of Smoking Status on Lung Cancer Staging in the Ninth Edition of the TNM Classification

Lawson Eng et al. J Thorac Oncol. 2025 Oct.

Abstract

Introduction: Cigarette smoking negatively affects lung cancer prognosis. Incorporating smoking history into stage-stratified survival analyses may improve prognostication.

Methods: Using the International Association for the Study of Lung Cancer ninth edition NSCLC database, we evaluated the association between smoking status at diagnosis and overall survival (OS) using Kaplan-Meier plots and multivariate Cox proportional hazard regression models adjusted for age, region, sex, histologic type, performance status, and TNM stage. Subgroup analyses evaluated within- and between-stage survival according to smoking status. Recursive partitioning analysis evaluated the effect of smoking relative to anatomical staging factors.

Results: Among 48,531 patients, 26%, 41%, and 34% currently, formerly, or never smoked, respectively; 75% had adenocarcinoma and 21%, squamous cell carcinoma. Compared with those who never smoked, those who currently (adjusted hazard ratio [aHR] = 1.39, 95% confidence interval [CI] [1.34-1.46], p < 0.0001) or formerly (aHR = 1.32, 95% CI: 1.27-1.36, p < 0.0001) smoked had worse OS. Current smoking was associated with worse OS (aHR = 1.05, 95% CI: 1.02-1.06] p = 0.005) compared with former smoking. These associations were consistent within each stage. In pair-wise comparisons, those who formerly or currently smoked had similar OS to patients in the next higher stage who never smoked. These associations remained consistent among patients from Asia, patients with adenocarcinoma, and both sexes. In recursive partitioning analysis, among patients with early stage (up to T3N1M0), smoking had greater prognostic impact than N0 versus N1 categories.

Conclusions: Smoking is an important prognostic factor and may be more impactful on prognosis than anatomical staging. Further exploration of combining smoking status with TNM classification for lung cancer is planned in the tenth edition International Association for the Study of Lung Cancer staging project.

Keywords: Lung cancer; Outcomes; Prognosis; Prognostic factors; Smoking; Staging; Tobacco.

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Conflict of interest statement

Disclosure Dr. Eng holds the Hold’em for Life Early Career Professorship in Cancer Research, a University Named Professorship at the University of Toronto. The work of Dr. Rusch is funded in part by the National Institutes of HealthCancer Center Support Grant P30-CA008748. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization. Where authors are identified as employees of the federal government of the United States, the views expressed are those of the author and not of the U.S. government.