Review

. 2024 Jul-Aug;74(4):359-367.

doi: 10.3322/caac.21840. Epub 2024 Apr 29.

Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors

Aman Chauhan¹, Kelley Chan², Thorvardur R Halfdanarson³, Andrew M Bellizzi⁴, Guido Rindi^{5

6}, Dermot O'Toole⁷, Phillip S Ge⁸, Dhanpat Jain⁹, Arvind Dasari¹⁰, Daniel A Anaya¹¹, Emily Bergsland¹², Erik Mittra¹³, Alice C Wei¹⁴, Thomas A Hope¹⁵, Ayse T Kendi¹⁶, Samantha M Thomas¹⁷, Sherlonda Flem¹⁸, James Brierley¹⁹, Elliot A Asare²⁰, Kay Washington²¹, Chanjuan Shi²²

Affiliations

¹ Department of Medicine, Neuroendocrine Oncology, Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, Florida, USA.
² Department of Surgery, Loyola University Medical Center, Chicago, Illinois, USA.
³ Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.
⁴ Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA.
⁵ Department of Life Sciences, Section of Anatomic Pathology, Università Cattolica del Sacro Cuore, Rome, Italy.
⁶ Department of Woman and Child Health Sciences and Public Health, Anatomic Pathology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS and Roma-Gemelli European Neuroendocrine Tumor Society Center of Excellence, Rome, Italy.
⁷ National Center for Neuroendocrine Tumors, European Neuroendocrine Tumor Society Center of Excellence (St Vincent's University Hospital) and St James Hospital, Trinity College Dublin, Dublin, Ireland.
⁸ Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁹ Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
¹⁰ Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
¹¹ Department of Gastrointestinal Oncology-Surgery, Moffitt Cancer Center, Tampa, Florida, USA.
¹² Department of Medicine, University of California San Francisco, San Francisco, California, USA.
¹³ Department of Diagnostic Radiology, Molecular Imaging and Therapy, Oregon Health and Science University, Portland, Oregon, USA.
¹⁴ Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
¹⁵ Department of Radiology, University of California San Francisco, San Francisco, California, USA.
¹⁶ Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
¹⁷ Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA.
¹⁸ Tumor Registrar, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
¹⁹ Radiation Medicine Program, Princess Margaret Cancer Center, University of Toronto, Toronto, Ontario, Canada.
²⁰ Department of Surgery, University of Utah, Salt Lake City, Utah, USA.
²¹ Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²² Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.

PMID: 38685134
PMCID: PMC11938941
DOI: 10.3322/caac.21840

Review

Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors

Aman Chauhan et al. CA Cancer J Clin. 2024 Jul-Aug.

. 2024 Jul-Aug;74(4):359-367.

doi: 10.3322/caac.21840. Epub 2024 Apr 29.

Authors

Affiliations

¹ Department of Medicine, Neuroendocrine Oncology, Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, Florida, USA.
² Department of Surgery, Loyola University Medical Center, Chicago, Illinois, USA.
³ Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.
⁴ Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA.
⁵ Department of Life Sciences, Section of Anatomic Pathology, Università Cattolica del Sacro Cuore, Rome, Italy.
⁶ Department of Woman and Child Health Sciences and Public Health, Anatomic Pathology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS and Roma-Gemelli European Neuroendocrine Tumor Society Center of Excellence, Rome, Italy.
⁷ National Center for Neuroendocrine Tumors, European Neuroendocrine Tumor Society Center of Excellence (St Vincent's University Hospital) and St James Hospital, Trinity College Dublin, Dublin, Ireland.
⁸ Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁹ Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
¹⁰ Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
¹¹ Department of Gastrointestinal Oncology-Surgery, Moffitt Cancer Center, Tampa, Florida, USA.
¹² Department of Medicine, University of California San Francisco, San Francisco, California, USA.
¹³ Department of Diagnostic Radiology, Molecular Imaging and Therapy, Oregon Health and Science University, Portland, Oregon, USA.
¹⁴ Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
¹⁵ Department of Radiology, University of California San Francisco, San Francisco, California, USA.
¹⁶ Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
¹⁷ Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA.
¹⁸ Tumor Registrar, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
¹⁹ Radiation Medicine Program, Princess Margaret Cancer Center, University of Toronto, Toronto, Ontario, Canada.
²⁰ Department of Surgery, University of Utah, Salt Lake City, Utah, USA.
²¹ Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²² Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.

PMID: 38685134
PMCID: PMC11938941
DOI: 10.3322/caac.21840

Abstract

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP-NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP-NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP-NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP-NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.

Keywords: American Joint Committee on Cancer (AJCC) version 9; cancer staging protocols; gastroenteropancreatic neuroendocrine tumors; gastrointestinal neuroendocrine tumor; pancreatic neuroendocrine tumor.

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Conflict of interest statement

CONFLICT OF INTEREST STATEMENT:

AC: Advisor for Ipsen, Lexicon, TerSera, Curium, Novartis, Seneca Therapeutics. Research support from BMS, Clovis, Allarity, EMD Serono, Nanopharmaceutics, Seneca Therapeutics

TRH: Research Support (to institution)-Thermo Fisher Scientific, Advanced Accelerator Applications (a Novartis company), Camurus, Crinetics, ITM Isotopen Technologien Muenchen; Consultancy/Advisory Board/Steering Committees (all but TerSera uncompensated or with payment to institution)-Ipsen, TerSera, Advanced Accelerator Applications (a Novartis company), ITM Isotopen Technologien Muenchen, Crinetics, Perspective Therapeutics, Camurus

GR: AAA speaker’s bureau, Bracco Imaging Suisse, consultant.

PG: consultant for Boston Scientific, Neptune Medical, Ovesco Endoscopy USA, Olympus America

AD: Research Support: Novartis, Eisai, Ipsen, Hutchison Pharma, Guardant Health, Natera; Consultant: Novartis, Ipsen, Voluntis, Abbvie, Crinetics, Hutchison Pharma, Personalis

TH: grant funding to the institution from Clovis Oncology, GE Healthcare, Lantheus, Janssen, the Prostate Cancer Foundation, and Telix Pharmaceuticals; personal fees from Bayer, Cardinal Health, BlueEarth Diagnostics, Lantheus and received fees from and has an equity interest in RayzeBio and Curium.

Other authors have no conflict of interest.

Figures

**Figure 1.**
Key milestones in neuroendocrine tumor diagnostics and therapeutics.

**Figure 2.**
WHO histopathological classification of digestive neuroendocrine neoplasms.

**Figure 3.**
Outcomes of gastroenteropancreatic neuroendocrine tumor (NET) subsets. A. Unadjusted 5-year overall survival by clinical stage group for gastric NETs. B. Unadjusted 5-year overall survival by clinical stage group for duodenal/ampullary NETs. C. Unadjusted 5-year overall survival by pathological stage group for pancreatic NETs. D. Unadjusted 5-year overall survival by pathological stage group for jejunal/ileal NETs. E. Unadjusted 5-year overall survival by pathological stage group for appendiceal NETs. F. Unadjusted 5-year overall survival by clinical stage group for colorectal NETs. Overall survival time was truncated at 5 years and censored marks were omitted for visualization. Data source: NCDB 2010–2016.

See this image and copyright information in PMC

References

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Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors

Affiliations

Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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Supplementary concepts

Grants and funding

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Full Text Sources

Medical

Research Materials