Validation and modification of staging Systems for Poorly Differentiated Pancreatic Neuroendocrine Carcinoma

BACKGROUND: The American Joint Committee on Cancer (AJCC) and the European Neuroendocrine Tumor Society (ENETS) staging classifications are two broadly used systems for pancreatic neuroendocrine tumors. This study aims to identify the most accurate and useful tumor–node–metastasis (TNM) staging system for poorly differentiated pancreatic neuroendocrine carcinomas (pNECs). METHODS: An analysis was performed to evaluate the application of the ENETS, 7th edition (7th) AJCC and 8th edition (8th) AJCC staging classifications using the Surveillance, Epidemiology, and End Results (SEER) registry (N = 568 patients), and a modified system based on the analysis of the 7th AJCC classification was proposed. RESULTS: In multivariable analyses, only the 7th AJCC staging system allocated patients into four different risk groups, although there was no significant difference. We modified the staging classification by maintaining the T and M definitions of the 7th AJCC staging and adopting new staging definitions. An increased hazard ratio (HR) of death was also observed from class I to class IV for the modified 7th (m7th) staging system (compared with stage I disease; HR for stage II =1.23, 95% confidence interval (CI) = 0.73–2.06, P = 0.44; HR for stage III =2.20, 95% CI =1.06–4.56, P = 0.03; HR for stage IV =4.95, 95% CI =3.20–7.65, P < 0.001). The concordance index (C-index) was higher for local disease with the m7th AJCC staging system than with the 7th AJCC staging system. CONCLUSIONS: The m7th AJCC staging system for pNECs proposed in this study provides improvements and may be assessed for potential adoption in the next edition.