Evaluation of Survival Following Surgical Resection for Small Nonfunctional Pancreatic Neuroendocrine Tumors

Abstract

Importance: The number of patients with small nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) is increasing. However, the role of surgery for small NF-PanNETs remains unclear.

Objective: To evaluate the association between surgical resection for NF-PanNETs measuring 2 cm or smaller and survival.

Design, setting, and participants: This cohort study used data from the National Cancer Database and included patients with NF-pancreatic neuroendocrine neoplasms who were diagnosed between January 1, 2004, and December 31, 2017. Patients with small NF-PanNETs were divided into 2 groups: group 1a (tumor size, ≤1 cm) and group 1b (tumor size, 1.1-2.0 cm). Patients without information on tumor size, overall survival, and surgical resection were excluded. Data analysis was performed in June 2022.

Exposures: Patients with vs without surgical resection.

Main outcomes and measures: The primary outcome was overall survival of patients in group 1a or group 1b who underwent surgical resection compared with those who did not, which was evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Interactions between preoperative factors and surgical resection were analyzed with a multivariable Cox proportional hazards regression model.

Results: Of the 10 504 patients with localized NF-PanNETs identified, 4641 were analyzed. These patients had a mean (SD) age of 60.5 (12.7) years and included 2338 males (50.4%). The median (IQR) follow-up time was 47.1 (28.2-71.6) months. In total, 1278 patients were in group 1a and 3363 patients were in group 1b. The surgical resection rates were 82.0% in group 1a and 87.0% in group 1b. After adjustment for preoperative factors, surgical resection was associated with longer survival for patients in group 1b (hazard ratio [HR], 0.58; 95% CI, 0.42-0.80; P < .001) but not for patients in group 1a (HR, 0.68; 95% CI, 0.41-1.11; P = .12). In group 1b, interaction analysis found that age of 64 years or younger, absence of comorbidities, treatment at academic institutions, and distal pancreatic tumors were factors associated with increased survival after surgical resection.

Conclusions and relevance: Findings of this study support an association between surgical resection and increased survival in select patients with NF-PanNETs measuring 1.1 to 2.0 cm who were younger than 65 years, had no comorbidities, received treatment at academic institutions, and had tumors of the distal pancreas. Future investigations of surgical resection for small NF-PanNETs that include the Ki-67 index are warranted to validate these findings.

Figure 1.. Flowchart of Patients Included in the Study Cohort

NF-PanNETs indicates nonfunctional pancreatic neuroendocrine tumors; PanNECs, pancreatic neuroendocrine carcinomas; and PanNENs, pancreatic neuroendocrine neoplasms.

Figure 2.. Kaplan-Meier Curves of Overall Survival Stratified by Surgery in Nonfunctional Pancreatic Neuroendocrine Tumors

HR indicates hazard ratio.

Figure 3.. Forest Plot of the Association of Surgery With Mortality in Subgroup Analyses

The plot was done on a log scale. The position of each square represents the point estimate of the outcome of surgery, and error bars represent 95% CIs. The vertical line indicates a hazard ratio of 1.0, which was the null hypothesis value. aHR indicates adjusted hazard ratio. ^aAll interactions were tested in 1 model, which was adjusted for age, sex, facility type, Charlson-Deyo index, tumor location, clinical lymph node metastasis, tumor differentiation, tumor histologic distribution, and chemotherapy type. The HR was estimated for each interaction coefficient using the unresected group as the reference.