Introduction: In 1996, the International Association for the Study of Lung Cancer (IASLC) launched a worldwide TNM staging project to inform the next edition (seventh) of the TNM lung cancer staging system. In this article, we describe the methods and validation approaches used and discuss the internal and external validity of the recommended changes.
Methods: The International Staging Committee agreed on a number of general principles that guided the decision-making process. Internal validity was addressed by visually assessing the consistency of Kaplan-Meier curves across database types, geographic regions and addressing external validity, by assessing the similarity of curves generated using the population-based Surveillance Epidemiology and End Results cancer registry data to those generated using the project database. Cox proportional hazards regression was used to calculate hazard ratios between the proposed stage groupings with adjustment for cell type, sex, age, and region.
Results: Calls for data by the International Staging Committee resulted in the creation of an international database containing information on more than 100,000 cases. The present work is based on analyses of the 67,725 cases of non-small cell lung cancer. Validation checks were robust, demonstrating that the suggested staging changes are stable within the data sources used and externally. For example, suggested changes based on tumor size were well supported, with statistically significant hazard ratios ranging from 1.14 to 1.51 between adjacent pairs in the Surveillance Epidemiology and End Results data.
Conclusions: Lung cancer stage definitions have never been subjected to such an intense validation process. We do accept, however, that this work is limited in ways that can only be addressed by a prospective database, which we intend to develop. In the meantime, we think that this new system will greatly improve the usefulness of TNM lung staging across all of its purposes.