Preliminary data on the diagnostic efficacy of F-18-rhPSMA-7.3 PET imaging for N-staging of Patients with Intermediate and High Risk Prostate Cancer compared to histopathology

1267 Purpose: Radiohybrid PSMA (rhPSMA) ligands are a new class of diagnostic/therapeutic PSMA-targeting agents, which can be efficiently labeled with F-18 and radiometals and show only minimal renal excretion. Promising preliminary data have been reported for F-18-rhPSMA-7, which comprises four isomers. Based on preclinical findings, F-18-rhPSMA-7.3 was selected as the lead rhPSMA compound for clinical development. Here we report first data investigating its efficacy for primary N-staging in patients with intermediate and high-risk prostate cancer. Results were compared to morphological imaging and validated by histopathology. Materials and Methods: 62 patients (median PSA 9.9 ng/mL, range: 2.4-51.3) with intermediate or high-risk prostate cancer (defined by D’Amico) underwent F-18-rhPSMA-7.3 PET-imaging (median injected activity 345.5 MBq; range: 240-449 MBq, median uptake time 74 min; range: 58-102 min) and were retrospectively rated by one experienced reader for the presence of lymph node metastases using a standard surgical template. Each anatomical field was rated on a five-point-scale independently for PET and for morphological imaging. Results were compared to histopathological findings after subsequent radical prostatectomy and extended pelvic lymph node dissection on patient-, R vs. -L, and template-base. Results: Lymph node metastases were present in 19/62 patients (30.6%), located in 36/354 templates (10.2%). On patient-based analysis the sensitivity, specificity and accuracy of F-18-rhPSMA-7.3-PET were 63.2%, 93.0% and 83.9%, and those of morphological imaging 31.6%, 90.7% and 72.6%, respectively. For the right vs. left analysis the sensitivity, specificity and accuracy of F-18-rhPSMA-7.3-PET were 61.5%, 96.9% and 89.5%, and for morphological imaging 26.9%, 95.9% and 81.5%, respectively. On template-based analysis the sensitivity, specificity and accuracy of F-18-rhPSMA7.3-PET were 55.6%, 98.1% and 93.8%, and those of morphological imaging 16.7%, 99.4% and 91.0%, respectively. On ROC analyses, F-18-rhPSMA-7.3-PET showed a clear trend towards a better performance than morphological imaging on patient-, R vs. L and template-based analyses, yielding AUC values of 0.798 vs. 0.723 (p=0.35), 0.796 vs. 0.666 (p=0.08) and 0.762 vs. 0.656 (p<0.05), respectively. Conclusions: Our preliminary data from this small cohort indicate that F-18-rhPSMA-7.3 PET might be superior to morphological imaging for primary N-staging of intermediate and high-risk prostate cancer. Data analysis from a larger cohort is planned to confirm this significant difference.