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

Haihong Wang,Guiling Li,Qili Lin,Tao Zhang,Jing Wang,Zhenyu Lin,Guoliang Pi,Ye Zhao,Dejun Zhang,Dandan Yu

doi:10.1186/s12885-020-6634-9

Abstract

BackgroundThe 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).MethodsAn 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.ResultsIn 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.ConclusionsThe m7th AJCC staging system for pNECs proposed in this study provides improvements and may be assessed for potential adoption in the next edition.

Highlights

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
Our data demonstrated that the 7th AJCC staging classification has better distribution of pancreatic neuroendocrine carcinomas (pNECs) with different stages compared with the ENETS and 8th AJCC staging systems
Some studies have already demonstrated the predictive value of lymph nodal status for pNENs was limited and that the nodal stage showed no distinguished differences on the we proposed an adjustment to the 7th AJCC staging classification by maintaining the T and M definitions but adopting a new staging definition system

Summary

Introduction

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. A TNM staging system specially for pNENs was first proposed in the year 2006 by the ENETS [12]. This staging system was validated to risk stratify patients and discriminate among prognostic groups for pNENs by several studies [2, 13,14,15,16,17,18,19]. The vast majority of participants used to inform the ENETS staging classification were diagnosed with pNETs. the ENETS staging system has been recommended by the National Comprehensive Cancer Network guidelines for pNETs. In 2010, the 7th AJCC staging system first staged pNENs and employed the same staging system as they used for exocrine pancreas malignancies [20,21,22]. The question regarding the suitable staging system specially for pNECs remain unanswered

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