PROSTATE CANCER - ADVANCED 8 General Session, Thu, 3:00 PM-4:25 PM Circulating tumor DNA (ctDNA) to detect neuroendocrine prostate cancer genomic and DNA methylation changes. Himisha Beltran, Alessandro Romanel, Vincenza Conteduca, Nicola Casiraghi, Michael Sigouros, Gian Marco Franceschini, Tarcisio Fedrizzi, sheng-Yu Ku, Alicia Alonso, Juan Miguel Mosquera, Emma Dann, Andrea Sboner, Jenny Xiang, Olivier Elemento, David M. Nanus, Scott T. Tagawa, Matteo Benelli, Francesca Demichelis; Dana-Farber Cancer Institute, Boston, MA; University of Trento, Trento, Italy; Dana Farber Cancer Institute, Boston, MA; Department of Medicine, Division of Medical Oncology, Weill Cornell Medicine, New York City, NY; Weill Cornell Medicine, New York, NY; Department of Pathology & Laboratory Medicine, Englander Institute for Precision Medicine, Weill Cornell Medical College & New York-Presbyterian Hospital, New York, NY; Weill Cornell Medical College, New York, NY; Department of Physiology and Biophysics, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, Weill Cornell Medical College, New York, NY; Sandra and Edward Meyer Cancer Center, New York, NY; Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy Background: Loss of androgen receptor signaling dependence occurs in approximately 20% of treatment resistant prostate cancers, and this may manifest as transformation to castration resistant neuroendocrine prostate cancer (CRPC-NE). The diagnosis of CRPC-NE relies on a metastatic tumor biopsy, which is invasive for patients. Here we study ctDNA as an approach to identify CRPC-NE-associated genomic and epigenomic changes. We also use this as a tool to understand tumor heterogeneity and clonal dynamics that occurs during CRPC-NE progression. Methods: 64 patients with metastatic prostate cancer (10 hormone naive, 35 castration resistant adenocarcinoma (CRPC-Adeno), 17 CRPC-NE) were prospectively enrolled for matched metastatic biopsy and blood collection. Twenty-four had multiple time-points, for total of 69 plasma and 98 metastatic tissues. Whole exome sequencing (WES) and whole genome bisulfite sequencing(of subset) of ctDNA,germline DNA, and metastatic biopsies were performed. Results: Overall there was high concordance of alterations between ctDNA and patient-matched metastasis, though this was highest in CRPC-NE. There was also less heterogeneity across patients with CRPC-NE. Alteration frequencies were consistent with published tissue-based studies with AR alterations enriched in CRPC-Adeno and TP53and RB1loss enriched in CRPC-NE ctDNA. The prognostic significance of these alterations differed based on histologic subtype. Allele-specific copy number analysis and serial sampling allowed for the detection and tracking of clonal and subclonal tumor cell populations. cfDNA methylation was reflective of methylation patterns in biopsies and detected CRPC-NE-associated epigenetic changes.A targeted set combining genomic (TP53, RB1, CYLD, AR) and epigenomic(20 differential DNA methylation sites) was capable of identifying patients with CRPC-NE. Conclusions: WES and whole genome methylation of ctDNA is feasible, concordant with biopsy tissues, and identifies the spectrum and frequency of CRPC-NE genomic and epigenomic changes. A targeted panel extended and validated in larger cohorts could potentially improve the detection of CRPC-NE using non-invasive ctDNA profiling. Research Sponsor: U.S. National Institutes of Health, Other Foundation. © 2020 American Society of Clinical Oncology. Visit gucasym.org and search by abstract for disclosure information. PROSTATE CANCER - ADVANCED 9 General Session, Thu, 7:45 AM-9:30 AM A prospective phase II/III multicenter study of PSMA-targeted 18F-DCFPyL PET/CT imaging in patients with prostate cancer (OSPREY): A sub-analysis of regional and distant metastases detection rates at initial staging by 18F-DCFPyL PET/CT. Frederic Pouliot, Peter Carroll, Stephan Probst, Kenneth J. Pienta, Steven P. Rowe, Lawrence Saperstein, Barry Siegel, Akash Patnaik, Mark A. Preston, Ajjai Shivaram Alva, Michael A. Gorin, Michael J. Morris; Cancer Research Center, Centre Hospitalier Universitaire (CHU) de Qu´ebec-Universit´e Laval, Quebec City, QC, Canada; University of California-San Francisco, San Francisco, CA; Jewish General Hospital, Montreal, QC, Canada; James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD; Yale School of Medicine, New Haven, CT; Siteman Cancer Center/Washington University, Saint Louis, MO; Beth Israel Deaconess Medical Center/Dana-Farber Cancer Institute, Boston, MA; Brigham and Women’s Hospital, Boston, MA; University of Michigan, Ann Arbor, MI; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD; Memorial Sloan Kettering Cancer Center, New York, NY Background: Current imaging modalities are suboptimal for the initial staging of men at risk of harboring occult metastatic prostate cancer (PCa). PSMA-based imaging is considered highly promising for PCa detection. 18F-DCFPyL is a novel PSMA-targeted radiopharmaceutical for positron emission tomography (PET) that may be useful in staging of pts with high risk PCa. The diagnostic performance of 18F-DCFPyL regarding regional and distant metastases has been previously reported. Here we report on detection rates and the resulting impact 18F-DCFPyL may have on staging of pts with high risk PCa. Methods: 18F-DCFPyL PET/CT was evaluated in 252 men with high-risk PCa who were planned for radical prostatectomy with lymphadenectomy (RP-PLND). 9 mCi (333 MBq) of 18F-DCFPyL was administered 1-2 hours prior to PET/CT. Based on TNM staging, 18F-DCFPyL PET/CT detection rates including lesion counts were systematically analyzed: prostatic (T), pelvic LN (N), extra-pelvic LN (M1a), bone (M1b) & other visceral organs/soft tissue (M1c). Three central, blinded, and independent readers evaluated the 18F-DCFPyL scans. Results: At study entry, 97% and 99% of all evaluable pts had no known nodal or metastatic disease, respectively, based on standard cross-sectional imaging. Of these, 18F-DCFPyL PET/CT staged 37 (14.7%) pts with N1 disease and 27 (10.7%) pts with M1 disease (1 [0.4%] M1a, 23 [9.1%] M1b, and 3 [1.2%] M1c). In total, 56 (22%) of patients were upstaged to N1 or M1 disease by 18F-DCFPyL. The positive predictive value of 18F-DCFPyL based on histopathologic validation for pelvic LNs was 86.7% (95% CI: 70, 95). Only one patient in Cohort A underwent a biopsy of their 18F-DCFPyL detected M1 finding; histopathology confirmed the metastatic lesion in the spine to be a true positive. Conclusions: A total of 22% of pts with high-risk PCa planned for RP-PLND had regional or distant metastatic lesions detected on 18F-DCFPyL PET/CT. These results suggest the potential utility of 18F-DCFPyL PET/CT in the staging of men with newly diagnosed high risk PCa to develop optimized treatment paradigms. Clinical trial information: NCT02981368. Research Sponsor: Progenics Pharmaceuticals, Inc. © 2020 American Society of Clinical Oncology. Visit gucasym.org and search by abstract for disclosure information. PROSTATE CANCER - ADVANCED 10 General Session, Thu, 10:00 AM-11:30 AM Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence (STOMP): Five-year results of a randomized phase II trial. Piet Ost, Dries Reynders, Karel Decaestecker, Valerie Fonteyne, Nicolaas Lumen, Aur´elie De Bruycker, Bieke Lambert, Louke Delrue, Ren´ee Bultijnck, Els Goetghebeur, Geert Villeirs, Kathia De Man, Filip Ameye, Ignace Billiet, Steven Joniau, Friedl Vanhaverbeke, Gert de Meerleer; Ghent University Hospital, Ghent, Belgium; Ghent University, Ghent, Belgium; Ghent University Hospital, Gent, Belgium; Department of Nuclear Medicine, AZ Maria-Middelares Ghent, Ghent, Belgium; Department of Radiology, Gent University Hospital, Gent, Belgium; Department of Human Structure and Repair, Ghent University, Ghent, Belgium; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium; Department of Nuclear Medicine, Ghent University Hospital, Gent, Belgium; Maria Middelares Ziekenhuis, Gent, Belgium; AZ Groeninge, Kortrijk, Belgium; University Hospitals Leuven, Leuven, Belgium; AZ NIKOLAAS, Sint-Niklaas, Belgium; Department of Human Structure and Repair, Ghent University, Gent, Belgium Background: Multiple randomized phase II trials suggest that metastasis-directed therapy (MDT) for oligometastatic prostate cancer (PCa) improves progression-free survival, but the majority of trials lack longer follow-up. We present the updated 5-year results from the STOMP-trial. Methods: In this multicentre, randomised, phase II study, asymptomatic PCa patients were eligible in case of a biochemical recurrence following primary PCa treatment with curative intent and presenting with up to 3 extracranial on choline PET-CT and a serum testosterone levels . 50 ng/ml. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions. Randomisation was balanced dynamically on two factors: PSA doubling time (#3 vs. 3 months) and nodal vs non- nodal metastases. The primary endpoint was androgen deprivation therapy (ADT)-free survival. Castrate resistant prostate cancer-free survival (CRPC) was a secondary endpoint. Tests were performed two-sided; p values less than 0.20 were deemed significant. Results: The