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Operative vs. Non-Operative Management of Nonfunctioning Pancreatic Neuroendocrine Tumors
Irene Y. Zhang*1, Carlos Fernandez-Del Castillo2, Jing Zhao3, Shadi Razmdjou2, Andrew L. Warshaw2, Keith D. Lillemoe2, Cristina R. Ferrone2
1Harvard Medical School, Boston, MA; 2Massachusetts General Hospital, Boston, MA; 3Harvard School of Public Health, Boston, MA
Background: Surgical resection is the only curative treatment for pancreatic neuroendocrine tumors (PNETs), but pancreatic operations are high risk, with up to a 40% complication rate. There are currently no guidelines for surgery vs. surveillance when small, asymptomatic nonfunctioning PNETs are identified. We therefore investigated when resection of nonfunctioning PNETs offers therapeutic benefit.
Methods: A retrospective review of all patients with nonfunctioning PNETs presenting between 1998-2014 was performed. Non-operative patients had at least one follow-up imaging study. Kaplan-Meier survival analysis was conducted, and clinicopathologic and treatment-related variables were tested for association with overall and disease-specific survival.
Results: A total of 251 patients with nonfunctioning PNETs were analyzed, including 195 operative and 56 non-operative cases. Median age was 56 years and 48% were female. Operative patients had a significantly longer overall survival than non-operative patients (p=0.0013). In multivariate models, metastasis was the only significant predictor of overall survival in each cohort (non-operative, p=0.0044; operative, p<0.0001). Surgery was a significant positive prognostic factor for overall survival (p=0.0016), after controlling for metastasis, tumor size, and age-adjusted Charlson Comorbidity Index (CCI), and for disease-specific survival (p=0.0007), after controlling for tumor size and CCI (all disease-specific deaths were associated with metastasis). In patients with small PNETs (≤3cm) and no metastasis at presentation, the population for which resection is debated, there was a significant statistical interaction between an operation and tumor size. In a systematic exploratory analysis, the hazard ratio associated with an operation decreased monotonically with increased tumor size, and an operation became a significant prognostic factor for overall survival for tumors over 1.5cm (p=0.029 or less for larger tumors) but was not significant for tumors under 1.5cm (p=0.657 or more for smaller tumors).
Conclusion: For small nonfunctioning PNETs, tumor size should be a key consideration in management decisions. Resection of nonfunctioning PNETs over 1.5cm is significantly associated with a longer survival; however, the benefit of resection for tumors under 1.5cm is unclear.
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