Reproducibility of PSMA PET/CT Imaging for Primary Staging of Treatment-Naive Prostate Cancer Patients Depends on the Applied Radiotracer: A Retrospective Study

Our purpose was to determine and compare the interobserver variability of 3 clinically frequently used radiotracers targeting the prostate-specific membrane antigen (PSMA), namely 18F-DCFPyL, 18F-PSMA-1007, and 68Ga-PSMA-11, in primary prostate cancer (PCa) staging. Methods: Patients with newly diagnosed PCa in whom PSMA PET/CT was per-formed for primary staging purposes were retrospectively included. All PSMA PET/CT images were centrally overread within a high-volume PCa center, and original reports (from referring hospitals) were compared with overread reports (from the overreading hospital). To assess the inter -observer variability, a Cohen K analysis was used. To study possible differences in interobserver variability between the 3 applied PSMA radio -tracers, multivariate logistic regression analyses were used. Results: In total, 584 patients with newly diagnosed PCa were included in the analysis. 18F-DCFPyL, 18F-PSMA-1007, and 68Ga-PSMA-11 were used in 205 (35.1%), 168 (28.8%), and 211 (36.1%) patients, respec-tively. The overall agreement (Cohen K analysis) for locoregional lymph node metastases, distant lymph node metastases, bone metastases, and visceral metastases was 0.86, 0.86, 0.80, and 0.46, respectively. 18F-PSMA-1007 showed a significantly increased inter -observer variability regarding bone metastases, compared with 18F-DCFPyL and 68Ga-PSMA-11 (P = 0.001 and 0.03, respectively). Additionally, 18F-PSMA-1007 showed a significantly increased inter -observer variability regarding overall agreement and locoregional lymph node metastases, compared with 18F-DCFPyL (P , 0.001 and P = 0.01, respectively). Conclusion: Interobserver variability differs among the 3 clinically frequently used PSMA radiotracers (18F-DCFPyL, 18F-PSMA-1007, and 68Ga-PSMA-11) in patients with newly diagnosed PCa. The agreement in bone metastases is significantly worse for 18F-PSMA-1007, mainly due to nonspecific tracer uptake in osseous structures. On the basis of our findings, PSMA PET/CT scans undertaken with 18F-PSMA-1007 in primary staging should be inter-preted carefully, and training on interpreting this specific PSMA radio -tracer is advised.