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Defining the Role of Lymphadenectomy for Pancreatic Neuroendocrine Tumors: An Eight-Institution Study of 695 Patients from the US Neuroendocrine Tumor Study Group

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

Abstract

Background

Preoperative factors that reliably predict lymph node (LN) metastases in pancreatic neuroendocrine tumors (PanNETs) are unclear. The number of LNs needed to accurately stage PanNETs has not been defined.

Methods

Patients who underwent curative-intent resection of non-functional PanNETs at eight institutions from 2000 to 2016 were analyzed. Preoperative factors associated with LN metastases were identified. A procedure-specific target for LN retrieval to accurately stage patients was determined.

Results

Of 695 patients who underwent resection, 33% of tumors were proximal (head/uncinate) and 67% were distal (neck/body/tail). Twenty-six percent of patients (n = 158) had LN-positive disease, which was associated with a worse 5-year recurrence-free survival (RFS; 60% vs. 86%; p < 0.001). The increasing number of positive LNs was not associated with worse RFS. Preoperative factors associated with positive LNs included tumor size ≥ 2 cm (odds ratio [OR] 6.6; p < 0.001), proximal location (OR 2.5; p < 0.001), moderate versus well-differentiation (OR 2.1; p = 0.006), and Ki-67 ≥ 3% (OR 3.1; p < 0.001). LN metastases were also present in tumors without these risk factors: < 2 cm (9%), distal location (19%), well-differentiated (23%), and Ki-67 < 3% (16%). Median LN retrieval was 13 for pancreatoduodenectomy (PD), but only 9 for distal pancreatectomy (DP). Given that PD routinely includes a complete regional lymphadenectomy, a minimum number of LNs to accurately stage patients was not identified. However, for DP, removal of less than seven LNs failed to discriminate 5-year RFS between LN-positive and LN-negative patients (less than seven LNs: 72% vs. 83%, p = 0.198; seven or more LNs: 67% vs. 86%; p = 0.002).

Conclusions

Tumor size ≥ 2 cm, proximal location, moderate differentiation, and Ki-67 ≥ 3% are preoperative factors that predict LN positivity in resected non-functional PanNETs. Given the 9–23% incidence of LN metastases in patients without such risk factors, routine regional lymphadenectomy should be considered. PD inherently includes sufficient LN retrieval, while DP should aim to remove seven or more LNs for accurate staging.

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Funding

Funding was provided in part by the Katz Foundation.

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Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Alexandra G. Lopez-Aguiar MD, MS, Mohammad Y. Zaidi MD, MS, Kenneth Cardona MD & Shishir K. Maithel MD

  2. Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    Eliza W. Beal MD & Mary Dillhoff MD

  3. Department of Surgery, Stanford University Medical Center, Stanford, CA, USA

    John G. D. Cannon MD & George A. Poultsides MD

  4. Department of Surgery, Virginia Mason Medical Center, Seattle, WA, USA

    Zaheer S. Kanji MD & Flavio G. Rocha MD

  5. Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

    Paula Marincola Smith MD & Kamran Idrees MD

  6. Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA

    Megan Beems MD & Clifford S. Cho MD

  7. Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Alexander V. Fisher MD & Sharon M. Weber MD

  8. Department of Surgery, Washington University School of Medicine, St Louis, MO, USA

    Bradley A. Krasnick MD & Ryan C. Fields MD

Authors
  1. Alexandra G. Lopez-Aguiar MD, MS
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  2. Mohammad Y. Zaidi MD, MS
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  3. Eliza W. Beal MD
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  6. George A. Poultsides MD
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  9. Paula Marincola Smith MD
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  11. Megan Beems MD
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  12. Clifford S. Cho MD
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  13. Alexander V. Fisher MD
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  14. Sharon M. Weber MD
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  15. Bradley A. Krasnick MD
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  16. Ryan C. Fields MD
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  17. Kenneth Cardona MD
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  18. Shishir K. Maithel MD
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Corresponding author

Correspondence to Shishir K. Maithel MD.

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Disclosures

This work was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Numbers UL1TR000454 and TL1TR000456. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Lopez-Aguiar, A.G., Zaidi, M.Y., Beal, E.W. et al. Defining the Role of Lymphadenectomy for Pancreatic Neuroendocrine Tumors: An Eight-Institution Study of 695 Patients from the US Neuroendocrine Tumor Study Group. Ann Surg Oncol 26, 2517–2524 (2019). https://doi.org/10.1245/s10434-019-07367-y

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  • DOI: https://doi.org/10.1245/s10434-019-07367-y

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