PSMA-targeted imaging with <sup>18</sup>F-DCFPyL-PET/CT in patients (pts) withbiochemically recurrent prostate cancer (PCa): A phase 3 study (CONDOR)—A subanalysis of correct localization rate (CLR) and positive predictive value (PPV) by standard of truth.
Authors: Frederic Pouliot, Michael A. Gorin, Steven P. Rowe, Lawrence Saperstein, David Josephson, Peter R. Carroll, Jeffrey Y.C. Wong, Austin R. Pantel, Steve Y. Cho, Kenneth L. Gage, Morand Piert, Andrei Iagaru, Janet H. Pollard, Vivien Wong, Jessica Jensen, Nancy Stambler, Michael J. Morris, Barry A. Siegel
Journal: Journal of Clinical Oncology (2021)

5023 Background: PSMA-targeted PET/CT is superior to conventional imaging modalities to localize biochemically recurrent (BCR) PCa after local therapy, particularly in pts with low PSA ( &lt; 2 ng/mL). However, few studies have reported PSMA-targeted PET/CT accuracy compared to a pre-specified rigorous standard of truth (SOT) including histopathology, correlative imaging or treatment response in this population. Here, we report the CLR and PPV of PSMA-targeted 18 F-DCFPyLPET/ CT, for each of the pre-defined SOT criteria for the CONDOR prospective phase 3 study. Methods: The study enrolled men with rising PSA after definitive therapy and negative or equivocal standard of care imaging (e.g., CT/MRI, bone scintigraphy, F-18 fluciclovine). A single 9 mCi (333 MBq) ± 20% dose of 18 F-DCFPyL was injected, followed by PET/CT 1-2 hours later. Pts with positive 18 F-DCFPyL-PET/CT scans based on local interpretation were scheduled for follow up within 60 days to verify suspected lesion(s) using a composite SOT. The primary endpoint was CLR defined as PPV with the requirement of anatomic lesion co-localization between 18 F-DCFPyL-PET/CT and the SOT. The SOT consisted of, in descending priority: 1) histopathology, 2) subsequent correlative imaging findings determined by twocentral readers, or 3) post-radiation PSA response. The trial was successful if the lower bound of the 95% confidence interval for CLR exceeded 20% for at least two of three independent, blinded central 18 F-DCFPyL-PET/CT reviewers. Results: 208 men (median PSA 0.8 ng/mL) underwent 18 F-DCFPyL-PET/CT and the study achieved its primary endpoint: CLR was between 84.8% to 87.0% (lower bound of 95% CI: 77.8%-80.4%) among the three 18 F-DCFPyL-PET/CT readers, against the composite SOT. The performance of 18 F-DCFPyL-PET/CT by CLR (≥1 lesion co-localized) and PPV (≥1 lesion confirmed) was maintained through all 3 SOT categories. Histopathology (N = 31): 78.6-82.8% and 92.9-93.3% for CLR and PPV, respectively; correlative imaging (N = 100): 86.1-88.6% and 87.0-89.5% for CLR and PPV, respectively; and PSA response (N = 1): 100% for both CLR and PPV. Further analyses of the correlative imaging results showed CLR remained high across the different modalities used a) 18 F-fluciclovine-PET/CT (N = 71): (86.8-90.9%); b) MRI (N = 23): (80.0-86.7%); and c) CT (n = 6): (80.0-100%). Conclusions: PSMA-targeted 18 F-DCFPyL-PET/CT detected and localized metastatic lesions with high CLR and PPV regardless of which criterion defined CLR that was used, in men with BCR who had negative or equivocal baseline imaging. Clinicaltrials.gov: NCT03739684 Clinical trial information: NCT03739684.