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Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies
Susumu Hijioka1, Daiki Yamashige1, Minoru Esaki2
1Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Background & Aims:
Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs.
Methods:
In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort.
Results:
In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate.
Conclusions:
NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.
Insights
Treatment for small pancreatic neuroendocrine neoplasms (PNENs) should consider tumor grade, not just size. Higher grades (NET-G2+) and larger sizes (≥15 mm) indicate higher risks of metastasis and recurrence, necessitating personalized strategies.
Area of Science:
- Gastroenterology
- Surgical Oncology
- Endocrinology
Background:
- Uncertainties remain regarding optimal treatment strategies for nonfunctioning small pancreatic neuroendocrine neoplasms (NF-spNENs) ≤20 mm.
- A large Japanese cohort was analyzed to address these uncertainties.
Purpose of the Study:
- To evaluate surgically resected NF-spNENs in a large Japanese cohort.
- To elucidate an optimal treatment strategy for NF-spNENs.
Main Methods:
- Retrospective analysis of patients who underwent pancreatectomy between January 1996 and December 2019.
- Inclusion of cases pathologically diagnosed with pNEN according to WHO 2019 classification.
- Analysis of 1014 patients from a multicenter Japanese study.
Main Results:
- NF-spNENs are heterogeneous; 82% were grade 1 (NET-G1) and 18% were grade 2 (NET-G2) or higher.
- Lymph node metastasis (N1) was significantly higher in NET-G2 (15.0%) vs NET-G1 (3.1%).
- Independent predictors for N1 included NET-G2+ and tumor diameter ≥15 mm; predictors for recurrence included multiple lesions, NET-G2+, tumor diameter ≥15 mm, and N1. Tumor grade was the sole independent predictor for survival.
Conclusions:
- Treatment strategies solely based on tumor size for NF-spNENs can be unreliable due to their heterogeneity.
- Personalized treatment strategies incorporating tumor grading are preferable for managing NF-spNENs.
- Optimal resection timing varied by grade: >20 mm for NET-G1 and >10 mm for NET-G2+; >15 mm for unknown preoperative grades.
