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Is There a Role for Surgical Resection of Grade 3 Neuroendocrine Neoplasms?

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

Abstract

Background

Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are aggressive tumors with poor survival outcomes for which medical management is generally recommended. This study sought to evaluate outcomes of surgically treated G3 GEP-NEN patients.

Methods

A single-institutional prospective NEN database was reviewed. Patients with G3 GEP-NENs based on World Health Organization (WHO) 2019 definitions included well-differentiated neuroendocrine tumors (G3NET) and poorly differentiated neuroendocrine carcinomas (G3NEC). Clinicopathologic factors were compared between groups. Overall survival from G3 diagnosis was assessed by the Kaplan-Meier method.

Results

Surgical resection was performed for 463 patients (211 G1, 208 G2, 44 G3). Most had metastatic disease at presentation (54% G1, 69% G2, 91% G3; p < 0.001). The G3 cohort included 39 G3NETs and 5 G3NECs, 22 of pancreatic and 22 of midgut origin. Median overall survival (mOS; in months) was 268.1 for G1NETs, 129.9 for G2NETs, 50.5 for G3NETs, and 28.5 for G3NECs (p < 0.001). Over the same period, 31 G3 patients (12 G3NETs, 19 G3NECs) were treated non-surgically, with mOS of 19.0 for G3NETs and 12.4 for G3NECs.

Conclusions

Surgical resection of G3 GEP-NENs remains controversial due to poor prognosis, and surgical series are rare. This large, single-institutional study found significantly lower mOS in patients with resected G3NENs than those with G1/G2 tumors, reflecting more aggressive tumor biology and a higher proportion with metastatic disease. The mOS for resected G3NETs and G3NECs exceeded historical non-surgical G3NEN series (mOS 11–19 months), suggesting surgery should be considered in carefully selected patients with G3NENs, especially those with well-differentiated tumors.

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Acknowledgements

This work was supported by the Iowa T32 Surgical Oncology Training Grant (CA148062-01 to CGT), Radiation Biology T32 Training Grant (CA078586 to SKS), and the Iowa Neuroendocrine SPORE Grant (P50 CA174521-01 to PHE, JSD, CC, TMO, AMB, and JRH).

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Author notes

  1. Deceased: Thomas M. O’Dorisio

Authors and Affiliations

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

    Luis C. Borbon MD, Catherine G. Tran MD, Scott K. Sherman MD, Po Hien Ear PhD & James R. Howe MD

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

    Chandrikha Chandrasekharan MD, Joseph S. Dillon MD & Thomas M. O’Dorisio MD

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

    Andrew M. Bellizzi MD

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  1. Luis C. Borbon MD
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Correspondence to James R. Howe MD.

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Supplementary Figure

. Overall Survival (OS) in 40 surgically resected G3 GEP-NEN patients by primary site. Red solid line shows patients with small-bowel neuroendocrine tumors (SBNETs); blue solid line shows patients with pancreatic neuroendocrine tumors (PNETs); blue dashed line shows patients with pancreatic neuroendocrine carcinomas (PNECs). Although there was a trend towards longer median OS (mOS) in patients with SBNETs compared with PNETs (59.4 months vs. 37.6 months, respectively), this difference was not statistically significant (p = 0.1). PNECs had a mOS of 7.29 months (compared with PNETs, p = 0.4) (PDF 169 kb)

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Borbon, L.C., Tran, C.G., Sherman, S.K. et al. Is There a Role for Surgical Resection of Grade 3 Neuroendocrine Neoplasms?. Ann Surg Oncol 29, 6936–6946 (2022). https://doi.org/10.1245/s10434-022-12100-3

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  • DOI: https://doi.org/10.1245/s10434-022-12100-3

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