{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:53:11Z","timestamp":1793159591948,"version":"4.5.0"},"reference-count":25,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>The phase 3 randomized EMBARK trial evaluated enzalutamide with or without leuprolide in high-risk nonmetastatic hormone-sensitive prostate cancer. Eligibility relied on conventional imaging, which underdetects metastatic disease compared with prostate-specific membrane antigen\u2013positron emission tomography (PSMA-PET).<\/jats:p><\/jats:sec>Objective<\/jats:title>To describe the staging information obtained by PSMA-PET\/computed tomography (PSMA-PET\/CT) in a patient cohort eligible for the EMBARK trial.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This post hoc, retrospective cross-sectional study included 182 patients from 4 prospective studies conducted from September 15, 2016, to September 27, 2021. All patients had recurrent prostate cancer after radical prostatectomy (RP), definitive radiotherapy (dRT), or salvage radiotherapy (SRT). Analysis was performed from January 2023 to July 2024.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Patients included had increasing prostate-specific antigen (PSA) levels greater than 1.0 ng\/mL (after RP and SRT) or 2.0 ng\/mL above the nadir value (after dRT), PSA doubling time of 9 months or less, and a serum testosterone level of 150 ng\/dL or greater. Exclusion criteria were distant metastatic disease on radiographic imaging and prior hormonal or systemic therapy.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Staging information obtained by PSMA-PET\/CT in patients with nonmetastatic disease according to conventional imaging.<\/jats:p><\/jats:sec>Results<\/jats:title>From 2002 patients screened, 182 (median age at PET\/CT scan, 69 years [IQR, 64-73 years]) were included. Median prescan PSA levels were 2.4 ng\/mL (IQR, 1.4-4.8 ng\/mL) after RP (n\u2009=\u200991), 6.9 ng\/mL (IQR, 3.5-18.5 ng\/mL) after dRT (n\u2009=\u200939), 2.6 ng\/mL (IQR, 1.6-5.2 ng\/mL) after RP and SRT (n\u2009=\u200952), and 2.8 ng\/mL (IQR, 1.7-6.6 ng\/mL) overall (n\u2009=\u2009182). Results of PSMA-PET were positive in 80% of patients (73 of 91) after RP, 92% of patients (36 of 39) after dRT, 85% of patients (44 of 52) after RP and SRT, and 84% of patients (153 of 182) overall. PSMA-PET detected any distant metastatic disease (miTxNxM1) in 34% of patients (31 of 91) after RP, 56% of patients (22 of 39) after dRT, 60% of patients (31 of 52) after RP and SRT, and 46% of patients (84 of 182) overall. Polymetastatic disease (\u22655 lesions) was found in 19% of patients (17 of 91) after RP, 36% of patients (14 of 39) after dRT, 23% of patients (12 of 52) after RP and SRT, and 24% of patients (43 of 182) overall.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In a cohort of patients with high-risk hormone-sensitive prostate cancer without evidence of metastatic disease by conventional imaging, PSMA-PET results were positive in 84% of patients, detected M1 disease stage in 46% of patients, and found polymetastatic disease (\u22655 lesions) in 24% of patients, suggesting that patients\u2019 high-risk nonmetastatic hormone-sensitive prostate cancers are understaged by conventional imaging. The results challenge the interpretation of previous studies, such as the EMBARK trial, and support the evolving role of PSMA-PET for patient selection in clinical and trial interventions in prostate cancer. Further studies are needed to assess its independent prognostic value and use for treatment guidance.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.52971","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T16:31:16Z","timestamp":1735921876000},"page":"e2452971","source":"Crossref","is-referenced-by-count":70,"title":["PSMA-PET\/CT Findings in Patients With High-Risk Biochemically Recurrent Prostate Cancer With No Metastatic Disease by Conventional Imaging"],"prefix":"10.1001","volume":"8","author":[{"given":"Adrien","family":"Holzgreve","sequence":"first","affiliation":[{"name":"Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles"},{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley 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Radiological Sciences, University of California, Los Angeles"},{"name":"Department of Nuclear Medicine, University of Duisburg\u2013Essen, Essen, Germany"},{"name":"Jonsson Comprehensive Cancer Center, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton P.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo\u00efc","family":"Djaileb","sequence":"additional","affiliation":[{"name":"Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Gafita","sequence":"additional","affiliation":[{"name":"Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Thin","sequence":"additional","affiliation":[{"name":"Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas G.","family":"Nickols","sequence":"additional","affiliation":[{"name":"Jonsson Comprehensive Cancer Center, University of California, Los Angeles"},{"name":"Department of Radiation Oncology, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amar U.","family":"Kishan","sequence":"additional","affiliation":[{"name":"Jonsson Comprehensive Cancer Center, University of California, Los Angeles"},{"name":"Department of Radiation Oncology, University of California, Los 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