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Background: With the popularization of lung cancer screening, more early-stage lung cancers are being detected. This study aims to compare three types of N classifications, including location-based N classification (pathologic nodal classification [pN]), the number of lymph node stations (nS)-based N classification (nS classification), and the combined approach proposed by the International Association for the Study of Lung Cancer (IASLC) which incorporates both pN and nS classification to determine if the nS classification is more appropriate for early-stage lung cancer. Methods: We retrospectively reviewed the clinical data of lung cancer patients treated at the Cancer Hospital, Chinese Academy of Medical Sciences between 2005 and 2018. Inclusion criteria was clinical stage IA lung adenocarcinoma patients who underwent resection during this period. Sub-analyses were performed for the three types of N classifications. The optimal cutoff values for nS classification were determined with X-tile software. KaplanâMeier and multivariate Cox analyses were performed to assess the prognostic significance of the different N classifications. The prediction performance among the three types of N classifications was compared using the concordance index (C-index) and decision curve analysis (DCA). Results: Of the 669 patients evaluated, 534 had pathological stage N0 disease (79.8%), 82 had N1 disease (12.3%) and 53 had N2 disease (7.9%). Multivariate Cox analysis indicated that all three types of N classifications were independent prognostic factors for prognosis (all P < 0.001). However, the prognosis overlaps between pN (N1 and N2, P = 0.052) and IASLC-proposed N classification (N1b and N2a1 [P = 0.407], N2a1 and N2a2 [P = 0.364], and N2a2 and N2b [P = 0.779]), except for nS classification subgroups (nS0 and nS1 [P < 0.001] and nS1 and nS >1 [P = 0.006]). There was no significant difference in the C-index values between the three N classifications (P = 0.370). The DCA results demonstrated that the nS classification provided greater clinical utility. Conclusion: The nS classification might be a better choice for nodal classification in clinical stage IA lung adenocarcinoma.
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OBJECTIVES: The newly released eighth edition of the American Joint Committee on Cancer TNM staging system for lung cancer seeks to improve prognostic accuracy but lacks external validation for small cell lung cancer (SCLC). Moreover, previous studies posed a few questions concerning survival differences for patients with specific site N3 node involvement or single-site metastasis (SSM) in different distant organs. The aim of this study was to validate the eighth edition of the TNM classification for SCLC in an independent multi-institutional cohort from China and answer the questions raised by the previous research. METHODS: Patients with SCLC from four Chinese cancer centers between 2009 and 2019 were reclassified according to the seventh and eighth edition of the TNM classification. Survival was estimated using the Kaplan-Meier method. Comparisons between adjacent categories and stage groups were performed using Cox proportional hazard regression. R2 statistics were calculated to evaluate the discriminating performance of editions. RESULTS: Of 3384 enrolled cases, 3358 had clinical stage, 537 had pathological stage, and 511 had both. Progressive deterioration of survival was observed with advancing of TNM categories and stages both in the seventh and the eighth edition. The eighth edition stages had a higher R2 statistic than the seventh edition (0.207 versus 0.197). Newly defined categories M1b and M1c and stages IIIC, IVA and IVB in the eighth edition discriminated groups with significantly different prognosis. Patients with N3 contralateral supraclavicular nodes had a significantly worse prognosis than those without (p = 0.032). For patients with single-site metastasis, liver involvement showed a worse prognosis compared to brain involvement (p = 0.030). CONCLUSIONS: Our study provided an external validation of the eighth edition of the TNM classification for lung cancer in Chinese patients with SCLC, and confirmed its improved prognostic accuracy compared with the seventh edition. Patients with N3 and M1b might represent heterogeneous populations that warrant further research.