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Surgical Management of G3 Gastroenteropancreatic Neuroendocrine Neoplasms: A Systematic Review and Meta-analysis

  • Endocrine Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are rare, aggressive tumors with poor prognosis. The World Health Organization 2017 and 2019 classifications further subdivided G3 NENs into G3 neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Current guidelines favor medical management in most of these patients, and the role of surgical management is not well defined. We performed a systematic literature review and meta-analysis of surgical management versus nonsurgical management for G3 GEP NENs.

Materials and Methods

A PRISMA-compliant systematic review of the MEDLINE, Embase, Scopus, and Cochrane Library databases (end-of-search date: 16 July 2021) was conducted. Individual patient survival data were reconstructed, and random-effects meta-analyses were performed.

Results

Fourteen studies comprising 1810 surgical and 910 nonsurgical patients were systematically reviewed. Publication bias adjusted meta-analysis of 12 studies (1788 surgical and 857 nonsurgical patients) showed increased overall survival (OS) after surgical compared with nonsurgical management for G3 GEP NENs [hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.31–0.53]. Subgroup meta-analyses showed increased OS after surgical management for both pancreatic and gastrointestinal primary sites separately. In another subgroup meta-analysis of G3 GEP NETs (not NECs), surgical management was associated with increased OS compared with nonsurgical management (HR 0.26, 95% CI 0.11–0.61).

Conclusions

Surgical management of G3 GEP NENs may provide a potential survival benefit in well-selected cases. Further research is needed to define which patients will benefit most from surgical versus nonsurgical management. The current literature is limited by inconsistent reporting of survival outcomes in surgical versus nonsurgical groups, tumor grade, differentiation, primary tumor site, and selection criteria for surgical and nonsurgical management.

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Acknowledgement

None.

Funding

Several authors (P.J.B., C.C., J.S.D., A.M.B., and J.R.H.) were supported by the Iowa SPORE for Neuroendocrine Tumors (P50 CA174521-01).

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Authors and Affiliations

  1. Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA

    Ioannis A. Ziogas MD, MPH

  2. Surgery Working Group, Society of Junior Doctors, Athens, Greece

    Ioannis A. Ziogas MD, MPH & Panagiotis T. Tasoudis MD

  3. Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA

    Luis C. Borbon MD, Scott K. Sherman MD, FACS & James R. Howe MD, FACS

  4. Department of Biostatistics, University of Iowa College of Public Health, Iowa City, IA, USA

    Patrick J. Breheny MS, PhD

  5. Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA

    Chandrikha Chandrasekharan MBBS & Joseph S. Dillon MD

  6. Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA

    Andrew M. Bellizzi MD

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  1. Ioannis A. Ziogas MD, MPH
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Contributions

IAZ: study design, literature search and study selection, data extraction, analysis and interpretation of data, drafting of the manuscript. PTT: literature search and study selection, data extraction, analysis and interpretation of data, critical revision of the manuscript. LCB: data extraction, analysis and interpretation of data, critical revision of the manuscript. SKS: analysis and interpretation of data, critical revision of the manuscript. PJB: analysis and interpretation of data, critical revision of the manuscript. Chandrikha Chandrasekharan: analysis and interpretation of data, critical revision of the manuscript. JSD: analysis and interpretation of data, critical revision of the manuscript. AMB: analysis and interpretation of data, critical revision of the manuscript. JRH: study design, literature search and study selection, analysis and interpretation of data, drafting of the manuscript.

Corresponding author

Correspondence to James R. Howe MD, FACS.

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Ziogas, I.A., Tasoudis, P.T., Borbon, L.C. et al. Surgical Management of G3 Gastroenteropancreatic Neuroendocrine Neoplasms: A Systematic Review and Meta-analysis. Ann Surg Oncol 30, 148–160 (2023). https://doi.org/10.1245/s10434-022-12643-5

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