Utility of <sup>18</sup>F-rhPSMA-7.3 PET for Imaging of Primary Prostate Cancer and Preoperative Efficacy in N-Staging of Unfavorable Intermediate- to Very High-Risk Patients Validated by Histopathology
Thomas Langbein, Hui Wang, Isabel Rauscher, Markus Kroenke, Karina Knorr, Alexander Wurzer, Kristina Schwamborn, Tobias Maurer, Thomas Horn, Bernhard Haller, Hans‐Jürgen Wester, Matthias Eiber
Abstract
<sup>18</sup>F-rhPSMA-7.3, the lead compound of a new class of radiohybrid prostate-specific membrane antigen (rhPSMA) ligands, is currently in phase III trials for prostate cancer (PCa) imaging. Here, we describe our experience in primary PCa staging. <b>Methods:</b> We retrospectively identified 279 patients with primary PCa who underwent <sup>18</sup>F-rhPSMA-7.3 PET/CT (staging cohort). A subset of patients (83/279) subsequently underwent prostatectomy with lymph node (LN) dissection without prior treatment (efficacy cohort). Distribution of tumor lesions was determined for the staging cohort and stratified by National Comprehensive Cancer Network (NCCN) risk score. Involvement of pelvic LN was assessed retrospectively by 3 blinded independent central readers, and a majority rule was used for analysis. Standard surgical fields were rated on a five-point scale independently for PET and for morphological imaging. Results were compared to histopathological findings on a patient-, right vs. -left, and template-basis. <b>Results:</b> For the staging cohort <sup>18</sup>F-rhPSMA-7.3 PET was positive in 275/279 (98.6%), 106/279 (38.0%), 46/279 (16.5%), 65/279 (23.3%) and 5/279 (1.8%) patients for local, pelvic nodal, extrapelvic nodal, metastatic bone, and visceral metastatic disease. In the efficacy cohort, LN metastases were present in 24/83 patients (29%), located in 48/420 (11%) resected templates and in 33/166 (19.9%) hemi-pelvic templates in histopathology. Based on majority vote results, the patient-level sensitivity, specificity and accuracy for pelvic nodal metastases were 66.7% (95%CI, 44.7-83.6%), 96.6% (95%CI, 87.3-99.4%) and 88.0% (95%CI, 78.5-93.8%) for <sup>18</sup>F-rhPSMA-7.3 PET and 37.5% (95%CI, 19.6-59.2%), 91.5% (95%CI, 80.6-96.8%) and 75.9% (95%CI, 65.0-84.3%) for morphological imaging, respectively. <sup>18</sup>F-rhPSMA-7.3 showed higher interobserver agreement than morphological imaging (patient-level Fleiss’ κ=0.54; 95%CI, 0.47-0.62 vs. 0.24; 95%CI, 0.17-0.31). A mean standardized uptake value ratio of 6.6 (95%CI, 5.2-8.1) documented a high image contrast between local tumors and adjacent low urinary tracer retention. <b>Conclusion:</b><sup>18</sup>F-rhPSMA-7.3 PET offers superior diagnostic performance to morphological imaging for primary N-staging of newly diagnosed PCa, shows lower inter-reader variation, and offers good distinction between primary tumor and bladder background activity. With increasing NCCN risk group an increasing frequency of extra-prostatic tumor lesions was observed.