Prognostic Value of F-18-FDG PET/CT in a Large Cohort of Patients with Advanced Metastatic Neuroendocrine Neoplasms Treated with Peptide Receptor Radionuclide Therapy

The objective of this retrospective study was to determine the role of F-18-FDG PET/CT in a large cohort of 495 patients with metastatic neuroendocrine neoplasms (NENs) who were treated with peptide receptor radionuclide therapy (PRRT) with a long-term follow-up. Methods: The 495 patients were treated with Lu-177- or Y-90-DOTATOC/DOTATATE PRRT between February 2002 and July 2018. All subjects received both Ga-68-DOTATOC/TATE/NOC and F-18-FDG PET/CT before treatment and were followed 3-189 mo. Kaplan-Meier analysis, log-rank testing (Mantel-Cox), and Cox regression analysis were performed for overall survival (OS) and progression-free survival (PFS). Results: One hundred ninety-nine patients (40.2%) presented with pancreatic NENs, 49 with cancer of unknown primary, and 139 with midgut NENs, whereas the primary tumor was present in the rectum in 20, in the lung in 38, in the stomach in 8, and in other locations in 42. F-18-FDG PET/CT was positive in 382 (77.2%) patients and negative in 113 (22.8%) before PRRT, whereas 100% were Ga-68-DOTATOC/TATE/NOC-positive. For all patients, the median PFS and OS, defined from the start of PRRT, were 19.6 mo and 58.7 mo, respectively. Positive F-18-FDG results predicted shorter PFS (18.5 mo vs. 24.1 mo; P = 0.0015) and OS (53.2 mo vs. 83.1 mo; P < 0.001) than negative F-18-FDG results. Among the cases of pancreatic NENs, the median OS was 52.8 mo in F-18-FDG-positive subjects and 114.3 mo in F-18-FDG-negative subjects (P = 0.0006). For all patients positive for F-18-FDG uptake, and a ratio of more than 2 for the highest SUVmax on Ga-68-somatostatin receptor (SSTR) PET to the most F-18-FDG-avid tumor lesions, the median OS was 53.0 mo, compared with 43.4 mo in those patients with a ratio of less than 2 (P = 0.030). For patients with no F-18-FDG uptake (complete mismatch imaging pattern), the median OS was 108.3 mo versus 76.9 mo for an SUVmax of more than 15.0 and an SUVmax of 15.0 or less on Ga-68-SSTR PET/CT, respectively. Conclusion: The presence of positive lesions on F-18-FDG PET is an independent prognostic factor in patients with NENs treated with PRRT. Metabolic imaging with F-18-FDG PET/CT complements the molecular imaging aspect of Ga-68-SSTR PET/CT for the prognosis of survival after PRRT. High SSTR expression combined with negative F-18-FDG PET/CT results is associated with the most favorable long-term prognosis.