[18F]-Fluorodeoxyglucose positron emission tomography in grade 1-2 pancreatic neuroendocrine tumors: Prognostic in grade 2, not predictive of systemic therapy benefit.

BACKGROUND: The clinical utility of [18F]-fluorodeoxyglucose positron emission tomography in well-differentiated pancreatic neuroendocrine tumors remains unclear. While its prognostic role is established in high-grade disease, its value in grade 1 and grade 2 pancreatic neuroendocrine tumors, particularly in guiding systemic therapy, requires further evaluation. METHODS: We retrospectively analyzed 140 consecutive patients with histologically confirmed grade 1 (n = 44, 31.4%) or grade 2 (n = 96, 68.6%) pancreatic neuroendocrine tumors (per the 2022 World Health Organization Classification of Tumors, Fifth Edition) who underwent baseline dual-tracer positron emission tomography/computed tomography (68Ga-DOTA-(Tyr3)-octreotate and [18F]-fluorodeoxyglucose) between 2018 and 2023 at a tertiary cancer center. The cohort represents 15.6% of all gastroenteropancreatic neuroendocrine tumors evaluated during the study period and was selected for dual-tracer imaging based on predefined clinical indications. Primary end points were overall survival and progression-free survival. RESULTS: [18F]-Fluorodeoxyglucose avidity was observed in 97 of 140 patients (69.3%), with significantly higher prevalence in grade 2 tumors (73/96, 76.0%) compared with grade 1 (24/44, 54.5%; χ2 = 5.58; P = .018). On multivariate analysis, [18F]-fluorodeoxyglucose avidity (hazard ratio, 9.74; P = .026) and skeletal metastases (22/140, 15.7%; hazard ratio, 3.62; P = .002) were independently associated with inferior overall survival. In grade 1 pancreatic neuroendocrine tumors, [18F]-fluorodeoxyglucose avidity did not influence prognosis, with 5-year overall survival of 90.7% and progression-free survival of 67.1% irrespective of [18F]-fluorodeoxyglucose uptake. In contrast, grade 2 [18F]-fluorodeoxyglucose-avid tumors (n = 73) demonstrated significantly worse outcomes compared with [18F]-fluorodeoxyglucose-negative counterparts (n = 23), with 5-year overall survival 61.5% versus not reached (P = .003) and median progression-free survival 41.2 months ([18F]-fluorodeoxyglucose avid) versus 94.8 months ([18F]-fluorodeoxyglucose negative); P = .006. Systemic chemotherapy (52/140, 37.1%) did not improve survival in [18F]-fluorodeoxyglucose-avid patients. Completion of ≥4 peptide receptor radionuclide therapy cycles (22/73, 30.1%) was associated with improved survival (5-year overall survival 72.6% vs 40.6%; P = .020); landmark analysis confirmed a directional progression-free survival benefit. CONCLUSION: [18F]-Fluorodeoxyglucose avidity is prognostically significant in grade 2 well-differentiated pancreatic neuroendocrine tumors but was not associated with improved outcomes following systemic chemotherapy in this retrospective cohort. In grade 1 tumors, [18F]-fluorodeoxyglucose avidity had no prognostic or therapeutic consequence. These findings support the prognostic rather than predictive role of [18F]-fluorodeoxyglucose positron emission tomography and requires prospective validation.