Assessing the Role of FET-PET Imaging in Glioblastoma Recurrence: A Retrospective Analysis of Diagnostic Accuracy and Clinical Utility

Introduction: Glioblastoma (GBM) remains a clinical challenge due to its high recurrence rate and the difficulty of distinguishing true progression from treatment-induced changes. 18-fluoride-fluoro-ethyl-tyrosine positron emission tomography (FET-PET) can clarify ambiguous findings from standard imaging by assessing metabolic activity. The aim of this study was to evaluate both sensitivity and specificity of FET-PET positive findings referenced with the target lesion histology. Methods: We performed a retrospective, single-center study correlating PET findings with histopathological results during multiple GBM recurrences. A molecular subgroup analysis stratified by MGMT status was conducted for “true-positive” and “true-negative” PET findings. Results: 960 patients with GBM were treated at our department between 2006 and 2021, of whom 347 (36.1% of total) had one tumor recurrence during follow-up with 156 (45.0%) FET-PET scans available. 95 patients (9.9%) had a second recurrence with a FET-PET conducted in 37 of these (39.0%), whereas 23 patients (2.4%) had a third recurrence with a FET-PET available in 8 patients (34.8%). For a positive FET-PET finding, the sensitivity achieved 95%, 96% and 83% in the first, second, and third recurrences, respectively, while the specificity amounted to 13%, 0%, and 0%. Stratification by molecular subtype revealed no differences in sensitivity (p=0.498 first recurrence, p=1.0 for second recurrence) or specificity (p=1.0 first recurrence, p=1.0) for MGMT status. Conclusion: PET imaging demonstrated high sensitivity for detecting GBM recurrence but showed variable specificity depending on the classification of uncertain cases. Notably, sensitivity declined with an increasing number of recurrences, suggesting that cumulative treatment effects and greater tumor heterogeneity over time may affect diagnostic performance. Further prospective studies are needed to refine diagnostic thresholds and improve clinical decision-making.