Utility of ¹⁸F-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

Abstract

18 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. Methods. We retrospectively identified 279 patients with primary PCa who underwent 18 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. Results. For the staging cohort 18 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 18 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. 18 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. Conclusion. 18 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.

Diagnostic Performance and Safety of 18 F-rhPSMA-7.3 Positron Emission Tomography in Men With Suspected Prostate Cancer Recurrence: Results From a Phase 3, Prospective, Multicenter Study (SPOTLIGHT)

“…Notably, 18 F-fluciclovine-PET was used more frequently (54% of patients with lesion follow-up) in the phase 3 registration trial for 18 F-DCFPyL. 18 As conventional imaging is less sensitive than 18 F-rhPSMA-7.3-PET, 21 the primary end points were likely impacted by the high number of lesions denoted FP on 18 F-rhPSMA-7.3-PET that would be considered TP if histopathology or a more sensitive imaging modality had been used as the predominant SoT. Lastly, as noted above, this trial was not designed to compare 18 F-rhPSMA-7.3-PET with existing PSMA-PET agents and in the absence of head-to-head comparisons caution should be applied in drawing comparisons based on individual trial data.…”

2023 FDA TIDES (Peptides and Oligonucleotides) Harvest

“…The technology was initially developed at the Technical University of Munich and then was out-licensed to Scintomics GmbH in 2017 [ 24 ]. Posluma showed high detection efficiency, even in patients with low PSMA levels [ 31 , 32 ], and its performance was comparable to the 68 Ga-PSMA-11 ( 68 Ga gozetotide) agent [ 31 , 32 ], which was approved in 2020 [ 29 ], as well as other PSMA ligands [ 33 ].…”

PSMA-targeted radiotheranostics in modern nuclear medicine: then, now, and what of the future?

“…Another study explored the utility of [ 18 F]-rhPSMA-7.3 for pre-operative efficacy for N staging in patients with unfavourable intermediate-to very high-risk profiles, as validated by histopathology. This research especially provided insights into primary PCa staging [72]. In May 2023, a significant milestone was achieved with [ 18 F]rhPSMA-7.3 FDA's approval (Posluma ® , Blue Earth Diagnostics) for the PET assessment of PSMA-positive lesions in patients with PCa who were receiving initial definitive therapy or who were experiencing suspected recurrence, as evidenced by elevated serum PSA levels.…”

“…Notably, the efficacy of [ 18 F]rhPSMA-7.3 in PET imaging has been subjected to various analyses, including a comparison of detection sensitivities on a right vs. left basis, where it demonstrated a sensitivity of 61.5% [77]. Additionally, its sensitivity for identifying pelvic nodal metastases was 66.7%, according to another study [72].…”