{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:45:56Z","timestamp":1792813556753,"version":"4.5.0"},"reference-count":24,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"18","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,6,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Randomized clinical trials (RCTs) have shown progression-free survival (PFS) benefits of metastasis-directed therapy (MDT) without androgen deprivation therapy for oligometastatic castration-sensitive prostate cancer (omCSPC). Most patients with bone metastatic (BM) omCSPC recur with additional bone disease after MDT. We hypothesized the BM-targeting alpha-emitter radium-223 dichloride (Ra223) could target subclinical bone disease and delay progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>This is an investigator-initiated, multicenter, open-label phase II RCT. Eligible men with recurrent omCSPC with \u2265one bone metastasis (\u2264three on conventional imaging and\/or \u2264five on molecular imaging) were randomly assigned (1:1) to stereotactic ablative radiation (SABR) MDT alone or SABR MDT with Ra223 (six cycles). Primary end point was composite PFS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      From August 9, 2019, to March 2, 2023, 64 patients were randomly assigned, 33 to SABR MDT and 31 to SABR MDT\/Ra223 balancing for key covariates. Most SABR MDT\/Ra223 patients (87%) received six cycles of Ra223. The median PFS was 11.8 months with SABR MDT and 10.5 months with SABR MDT\/Ra223 (adjusted hazard ratio [aHR], 1.42 [95% CI, 0.79 to 2.56];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .24). Seven patients (11%) experienced grade 3 treatment-related adverse events (no grade 4 or 5), 2 of 33 (6%) with SABR and 5 of 30 (17%) with SABR MDT\/Ra223. Patients with high-risk (HiRi) pathogenic mutations in\n                      <jats:italic toggle=\"yes\">ATM<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">BRCA1\/2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">RB1<\/jats:italic>\n                      , or\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      had worse PFS (HR, 5.95 [95% CI, 1.83 to 19.3];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .003). Greater T-cell receptor (TCR) unique productive rearrangements were prognostic for improved PFS independent of the treatment arm (aHR, 0.45 [95% CI, 0.21 to 0.96];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .04).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Adding Ra223 to SABR MDT in BM omCSPC does not delay progression of disease. We provide evidence for an HiRi mutational signature and TCR repertoire as prognostic biomarkers in omCSPC treated with SABR MDT, highlighting the importance of collecting biological correlates in RCTs for omCSPC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-00131","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T15:59:07Z","timestamp":1746633547000},"page":"2059-2068","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":29,"title":["Outcomes of Radium-223 and Stereotactic Ablative Radiotherapy Versus Stereotactic Ablative Radiotherapy for Oligometastatic Prostate Cancers: The RAVENS Phase II Randomized Trial"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct04037358","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9038-4674","authenticated-orcid":true,"given":"Jarey H.","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5115-1691","authenticated-orcid":true,"given":"Alexander D.","family":"Sherry","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8425-8281","authenticated-orcid":true,"given":"Soha","family":"Bazyar","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4021-5909","authenticated-orcid":true,"given":"Philip","family":"Sutera","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD"},{"name":"Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noura","family":"Radwan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4895-9838","authenticated-orcid":true,"given":"Ryan M.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic, Rochester, 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