Multimodality management, recurrence patterns, and long-term outcome of gastroenteropancreatic neuroendocrine neoplasms: Progress over 17 years

  • Gunjan S. DesaiEmail author
  • Prasad Pande
  • Verushka Chhabra
  • Rajiv C. Shah
  • Palepu Jagannath
Original Article



Many advances in the management of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) happened in the last two decades. This study highlights the progress in its management over 17 years, outcomes, recurrence patterns, and follow up protocols.


This retrospective analysis of prospectively maintained database at a single tertiary center included GEP-NEN patients from January 2001 to August 2017. Management protocols were based on European Neuroendocrine Tumor Society guidelines. Recurrences were categorized as follows: localized nodal, regional, distant hepatic, or combined. Patients were divided into cohorts: cohort 1 (2001–2006), cohort 2 (2007–2011), and cohort 3 (2012–2017). Survival patterns were analyzed.


One hundred and ninety-two patients were included with 98 (51.04%) grade (G) 1, 64 (33.34%) G2, and 30 (15.63%) G3. One hundred and four (54.16%) underwent curative surgery (58 G1, 27 G2, and 19 G3). Overall follow up ranged from 3 to 276 months; 39 were lost to follow up. Ninety-six patients had recurrences: 44 regional + distant and 40 liver-limited recurrences. One-, 3-, and 5-year survivals show significant differences among different treatment groups (p < 0.05). Significant increase in curative resections, chemotherapy utilization, and reduced recurrences were noted in cohort 3. Curative (R0) resection offered 1- and 3-year overall survival of 93.3% and 66.7% in cohort 1; 95.8% and 83.1% in cohort 2; and 100% and 92.9% in cohort 3.


Curative resection is the most significant factor for improved survival. Debulking surgerical procedure have a role whereas upfront peptide receptor radionuclide therapy is questionable. Chemotherapy improves overall survival in inoperable/metastatic setting. Recurrence patterns indicate that a long-term follow up greater than 10 years is necessary.


Liver metastasis Neuroendocrine neoplasms Recurrence patterns Survival analysis 


Compliance with ethical standards

Conflict of interest

GSD, PP, VC, RCS, and PJ declare that they have no conflict of interest.

Grants/other financial support

Financial support for this study was provided by an educational grant from the “Hepato-Pancreato-Biliary Training, Education and Research Foundation (HPB TERF).”

Ethics statement

The study was performed in a manner conforming to the Helsinki Declaration of 1975, as revised in 2000 and 2008, concerning human and animal rights, and the authors followed the policy concerning informed consent as shown in


The authors are solely responsible for the data and the content of the paper. In no way, the Honorary Editor-in-Chief, Editorial Board Members, or the printer/publishers are responsible for the results/findings and content of this article.


  1. 1.
    Hallet J, Law CH, Cukier M, et al. Exploring the rising incidence of neuroendocrine tumors: a population-based analysis of epidemiology, metastatic presentation, and outcomes. Cancer. 2015;121:589–97.CrossRefGoogle Scholar
  2. 2.
    Yang Z, Tang LH, Klimstra DS. Gastroenteropancreatic neuroendocrine neoplasms: historical context and current issues. Semin Diagn Pathol. 2013;30:186–96.CrossRefGoogle Scholar
  3. 3.
    Janson E, Sorbye H, Welin S, et al. Nordic guidelines 2014 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms. Acta Oncol. 2014;53:1284–97.CrossRefGoogle Scholar
  4. 4.
    Pasricha G, Padhi P, Daboul N, Monga DK. Management of well-differentiated gastroenteropancreatic neuroendocrine tumors (GEPNETs): a review. Clin Ther. 2017;39:2146–57.CrossRefGoogle Scholar
  5. 5.
    Zandee W, de Herder W. The evolution of neuroendocrine tumor treatment reflected by ENETS guidelines. Neuroendocrinology. 2018;106:357–65.CrossRefGoogle Scholar
  6. 6.
    Lee S, Kulkarni H, Singh A, et al. Theranostics of neuroendocrine tumors. Visc Med. 2017;33:358–66.CrossRefGoogle Scholar
  7. 7.
    Sigel C, Krauss Silva V, Reid M, et al. Assessment of cytologic differentiation in high-grade pancreatic neuroendocrine neoplasms: a multi-institutional study. Cancer Cytopathol. 2017;126:44–53.CrossRefGoogle Scholar
  8. 8.
    Palepu J, Shrikhande S, Bhaduri D, et al. Trends in diagnosis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in India: a report of multicenter data from a web-based registry. Indian J Gastroenterol. 2017;36:445–51.CrossRefGoogle Scholar
  9. 9.
    Frilling A, Åkerström G, Falconi M, et al. Neuroendocrine tumor disease: an evolving landscape. Endocr Relat Cancer. 2012;19:R163–85.CrossRefGoogle Scholar
  10. 10.
    Singh S, Moody L, Chan D, et al. Follow-up recommendations for completely resected gastroenteropancreatic neuroendocrine tumors. JAMA Oncol. 2018;4:1597–604.CrossRefGoogle Scholar
  11. 11.
    Alexandraki K, Karapanagioti A, Karoumpalis I, et al. Advances and current concepts in the medical management of gastroenteropancreatic neuroendocrine neoplasms. Biomed Res Int. 2017;2017:1–12.CrossRefGoogle Scholar
  12. 12.
    Berber E, Karabulut K, Aucejo F, McLennan G, Akyildiz H, Siperstein A. Multimodality treatment of neuroendocrine liver metastasis. J Surg Res. 2011;165:173.CrossRefGoogle Scholar
  13. 13.
    Frilling A, Clift A. Therapeutic strategies for neuroendocrine liver metastases. Cancer. 2015;121:1172–86.CrossRefGoogle Scholar
  14. 14.
    Mayo S, Herman J, Cosgrove D, et al. Emerging approaches in the management of patients with neuroendocrine liver metastasis: role of liver-directed and systemic therapies. J Am Coll Surg. 2013;216:123–34.CrossRefGoogle Scholar
  15. 15.
    Frilling A, Clift A. Therapeutic strategies for neuroendocrine liver metastases. Cancer. 2014;121:1172–86.CrossRefGoogle Scholar
  16. 16.
    Mayo S, Cameron A, Pawlik T. Neuroendocrine liver metastasis: transplant as part of multimodality liver-directed therapy. Arch Surg. 2012;147:98–9.CrossRefGoogle Scholar
  17. 17.
    Begum N, Maasberg S, Plöckinger U, et al. The influence of surgical intervention on long-term outcome of gastroenteropancreatic neuroendocrine neoplasia (NEN) in a large German multi center cohort study. Exp Clin Endocrinol Diabetes. 2013;121(03).Google Scholar
  18. 18.
    Rinke A, Müller H, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID study group. J Clin Oncol. 2009;27:4656–63.CrossRefGoogle Scholar
  19. 19.
    Caplin M, Pavel M, Ćwikła J, et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371:224–33.CrossRefGoogle Scholar
  20. 20.
    Pavel M, Hainsworth J, Baudin E, et al. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet. 2011;378:2005–12.CrossRefGoogle Scholar
  21. 21.
    Bergsma H, van Vliet E, Teunissen J, et al. Peptide receptor radionuclide therapy (PRRT) for GEP-NETs. Best Pract Res Clin Gastroenterol. 2012;26:867–81.CrossRefGoogle Scholar
  22. 22.
    Singh S, Chan D, Moody L, et al. Recurrence in resected gastroenteropancreatic neuroendocrine tumors. JAMA Oncol. 2018;4:583–5.CrossRefGoogle Scholar

Copyright information

© Indian Society of Gastroenterology 2019

Authors and Affiliations

  1. 1.Department of Gastrointestinal SurgeryLilavati Hospital and Research CenterMumbaiIndia
  2. 2.Department of Gastrointestinal SurgeryMPCT HospitalNavi MumbaiIndia
  3. 3.Department of General SurgeryPrime HospitalDubaiUAE
  4. 4.Department of Surgical OncologyLilavati Hospital and Research CentreMumbaiIndia

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