The International Association for the Study of Lung Cancer Staging Project: The Database and Proposal for the Revision of the Staging of Pulmonary Neuroendocrine Carcinoma in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer

Introduction: Pulmonary high-grade neuroendocrine carcinoma (NEC) includes SCLC and large cell NEC (LCNEC). The seventh and eighth editions of the TNM classification for lung cancer confirmed the applicability of this staging system for SCLC. With the proposal of N2 and M1c subcategories for the ninth edition classification, we assessed the applicability to NECs. Methods: The database included NEC cases diagnosed between January 2011 and December 2019. Eligible cases, with valid survival time and eighth edition TNM stage, were classified as pure SCLC, combined SCLC with NSCLC, and LCNEC. Survival was calculated using the Kaplan-Meier method, pairwise differences using a log-rank test, and prognostic groups using a Cox regression analysis. Results: There were 6181 pure and combined SCLC and 697 LCNEC cases available. For SCLC, survival outcome analyses included 4453 cases with clinical stage and 583 with pathologic stage data. The corresponding numbers for LCNEC were 585 and 508. The SCLC data validated the ninth edition classification for lung cancer, including the proposed new subcategories, N2a, single-station ipsilateral mediastinal or subcarinal lymph node involvement, and N2b, involvement of multiple ipsilateral or subcarinal stations. The data also validated the subcategorization of M1c into M1c1 (multiple lesions in a single extrathoracic organ system) and M1c2 (involvement of multiple extrathoracic organ systems). The LCNEC data were insufficient for complete survival analysis, but the available data reported decreasing survival with increasing clinical and pathologic stages. Conclusions: The ninth edition TNM classification applies to patients with NEC and is the appropriate standard for use in clinical practice.