30: Cytoreduction in Patients with Metastatic Pancreatic Neuroendocrine Tumors and the Clinical Factors Driving Outcomes

Introduction: Effective treatment for metastatic pancreatic neuroendocrine tumors (PNETs) often requires multidisciplinary and multimodality strategies. The impact of surgical cytoreduction on outcomes in metastatic PNET continues to be debated. Our objective was to evaluate clinical factors that would affect patient selection, extent of cytoreductive surgery, and outcomes.


Methods: A retrospective review of PNET patients diagnosed and treated at our neuroendocrine subspecialty center between 1998-2020 was performed. Among 372 PNET patients identified, 180 patients with metastatic PNET at diagnosis were included. Statistical analyses were performed to further identify several risk factors for survival.


Results: The mean age at diagnosis was 53 ± 12 years. Mean follow-up was 5.7 ± 5.5 years (range, 1 month-42 years). At last follow-up, 69 patients (38%) received primary resection alone, 66 (57%) hepatectomy alone, and 37 (21%) primary resection and hepatectomy. On multivariate analysis, cytoreduction (n=103) improved overall survival (OS) (HR: 0.48; 0.26-0.89) compared to patients who did not undergo cytoreduction (n=77); 74% (76/103) of these patients received >70% cytoreduction, which further improved OS (HR: 0.39; 0.20-0.74). Of all clinical factors, high-grade disease (n=36) was the strongest risk factor for worse OS (HR: 4.10; 2.15-7.85); in these patients, >70% cytoreduction maintained improved OS (HR: 0.06; 0.01-0.34). In patients without high-grade disease, poor tumor differentiation resulted in worse OS (HR: 2.76; 1.03-7.38). Patient factors such as age, race, sex, and comorbidities did not affect OS. Resection of the primary yielded no effect on OS, regardless of resection type. Postoperative complications occurred in 27% (46/172).


Conclusions: With careful patient selection, cytoreduction >70% resulted in improved OS, even in patients with high-grade disease. No clear OS benefit was observed with resection of the primary in the metastatic setting. Defining patient selection and extent of cytoreduction with reasonable morbidity remain key drivers of patient management and are the focus of future research.