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

Abstract

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. <b>Methods:</b> Patients with newly diagnosed PCa in whom PSMA PET/CT was performed 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 interobserver variability, a Cohen κ analysis was used. To study possible differences in interobserver variability between the 3 applied PSMA radiotracers, multivariate logistic regression analyses were used. <b>Results:</b> 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, respectively. The overall agreement (Cohen κ 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 interobserver variability regarding bone metastases, compared with ¹⁸F-DCFPyL and ⁶⁸Ga-PSMA-11 (<i>P =</i> 0.001 and 0.03, respectively). Additionally, ¹⁸F-PSMA-1007 showed a significantly increased interobserver variability regarding overall agreement and locoregional lymph node metastases, compared with ¹⁸F-DCFPyL (<i>P</i> &lt; 0.001 and <i>P</i> = 0.01, respectively). <b>Conclusion:</b> 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 interpreted carefully, and training on interpreting this specific PSMA radiotracer is strongly advised.