Improvement of pathological staging system for neuroendocrine tumors of the lung

Background: Currently, the tumor, node, and metastasis (TNM) staging system has a limited value in prognostic stratification for neuroendocrine tumors of the lung (NETL). A specific pathological staging system was therefore explored. Methods: Two cohorts were assessed: the training cohort was composed of surgically treated patients from the Surveillance, Epidemiologic, and End Results (SEER) database [2004-2015]; the Shanghai cohort included Shanghai resident patients treated at Shanghai Pulmonary Hospital [2009-2018]. Multivariable Cox regression analysis was performed to identify factors associated with overall survival. A new staging system was proposed based on survival tree, and was further compared with the 8th edition of the TNM staging system. Results: In the training set (n=3,204), multivariate Cox analysis showed that tumor histotype and nodal status were independently associated with survival, but not T stage. Therefore, by incorporating NETL histotype (G1, low-grade typical pulmonary carcinoids; G2, intermediate-grade atypical pulmonary carcinoids; G3, high-grade large-cell neuroendocrine carcinomas) and N stage, a new staging system was developed: IA, G1N0; IB, G1N1 or G2N0; II, G1N2, G2N1-2, or G3N0; III, G3N1-2. Five-year survival rates were 91.2%, 81.3%, 50.2% and 27.6% for the new stages IA to III in the validation set (n=3,204), respectively (P<0.001). Additionally, the new staging system had significantly better predictive ability than the TNM staging system, in both the SEER [C-index, 0.75 vs. 0.62; net reclassification improvement (NRI), 0.62; integrated discrimination improvement (IDI), 20%] and Shanghai (IDI, 8%) cohorts. Based on the new staging system, adjuvant chemotherapy conferred a significantly better survival in stage-III NETL cases (HR =0.34, 95% CI, 0.25-0.45). Conclusions: The new pathological staging system can better predict NETL prognosis than the 8th edition of the TNM staging system, with the potential to guide postoperative treatment.

Automated summary

A new pathological staging system for neuroendocrine tumors of the lung has been developed and shown to have better prognostic value than the traditional TNM staging system. This system can potentially guide postoperative treatment decisions for patients with NETL.