Sporadic Small (≤20 mm) Nonfunctioning Pancreatic Neuroendocrine Neoplasm: is the Risk of Malignancy Negligible When Adopting a More Conservative Strategy? A Systematic Review and Meta-analysis

Ann Surg Oncol. 2017 Sep;24(9):2603-2610. doi: 10.1245/s10434-017-5946-8. Epub 2017 Jul 5.


Background: The management of small (≤20 mm), nonfunctioning pancreatic neuroendocrine neoplasms (pNENs) remains under debate. The European Neuroendocrine Tumor Society guidelines advocate the possibility of a conservative approach.

Methods: A systematic literature search was conducted to identify all studies comparing the risk of malignancy in small pNENs with respect to large ones (>20 mm). Malignancy was defined based on the presence of nodal metastases. Distant metastases, tumor grading (G2-3), vascular microscopic invasion, stage III-IV, and overall and disease-free survival also were evaluated. The data were reported in two ways: using the risk difference (RD) and the likelihood of being helped or harmed (LHH).

Results: The search identified only 6 eligible studies with an overall population of 1697 resected pNENs: 382 (22.5%) small and 1315 (77.5%) large. The RD of lymph nodal metastases was -0.26 (95% confidence interval (CI): -0.31 to -0.22; P < 0.001). The LHH was 0.34, suggesting that the risk of leaving a malignancy during follow-up due to the adoption of a conservative strategy was three times higher than the benefits. The risk difference of distant metastases, G3 lesions, G2-G3 lesions, stage III/IV, microscopic vascular invasion, death, and recurrence of the disease were lower in small NF-PNETs than large ones. The related LHH values suggested that a watch-and-wait policy never provided a benefit.

Conclusions: Even if the malignancy rate in sporadic, small pancreatic neuroendocrine neoplasms was lower than in large ones, this difference did not justify a watch-and-wait policy.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Conservative Treatment*
  • Humans
  • Lymphatic Metastasis
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neuroendocrine Tumors / secondary*
  • Neuroendocrine Tumors / surgery
  • Neuroendocrine Tumors / therapy*
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / surgery
  • Pancreatic Neoplasms / therapy*
  • Risk Assessment
  • Survival Rate
  • Tumor Burden