The IASLC Lung Cancer Staging Project: Proposals for the Revision of the M Descriptors in the Forthcoming 9th edition of the TNM Classification of Lung Cancer

Introduction This study analyzed all metastatic categories of the current tumor, node, and metastasis (TNM) classification of non-small cell lung cancer to propose modifications of the M component in the next edition (9th) of the classification. Methods A database of 124,581 patients diagnosed between 2011 and 2019 was established; of these, 14,937 with NSCLC in stage IVA-IVB were available for this analysis. Overall survival was calculated using the Kaplan-Meier method, and prognosis assessed using multivariable-adjusted Cox proportional hazards regression. Results The 8th edition M categories demonstrated good discrimination in the 9th edition dataset. Assessments demonstrated that an increasing number of metastatic lesions was associated with decreasing prognosis; because this appears to be a continuum and adjustment for confounders was not possible, no specific lesion number was deemed appropriate for stage classification. Among tumors involving multiple metastases, decreasing prognosis was seen with an increasing number of organ systems involved. Multiple assessments, including after adjustment for potential confounders, demonstrated that patients with M1c patients who had metastases to a single extrathoracic organ system were prognostically distinct from M1c patients who had involvement of multiple extrathoracic organ systems. Conclusions These data validate the 8th edition M1a and M1b categories, that are recommended to be maintained. We propose the M1c category be divided into M1c1 (involvement of a single extrathoracic organ system) and M1c2 (involvement of multiple extrathoracic organ systems).