{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:47:56Z","timestamp":1791805676982,"version":"4.3.4"},"reference-count":27,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Radiotherapy is established as a standard treatment for low\u2010volume metastatic hormone\u2010sensitive prostate cancer (mHSPC), but its prognostic impact for high\u2010volume mHSPC under upfront therapy is unclear. This study investigates the effect of adding prostate\u2010directed radiotherapy (PDRT) with or without metastasis\u2010directed radiotherapy (MDRT) to upfront doublet therapy for high\u2010volume mHSPC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively assessed 239 patients who received upfront doublet therapy for synchronous high\u2010volume mHSPC between 2018 and 2025. Patients were divided into a PDRT (with or without MDRT;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200932) and a non\u2010PDRT group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009207). The primary endpoint was castration resistance\u2010free survival (CRFS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The median time from treatment initiation for mHSPC to PDRT initiation was 7.0 months. We excluded 31 patients from the non\u2010PDRT group who progressed to castration\u2010resistant prostate cancer within 7.0 months. Our 7\u2010month landmark analysis found significantly prolonged CRFS in the PDRT group compared with the non\u2010PDRT group in a propensity score\u2010matched cohort (hazard ratio [HR] 0.47, 95% CI: 0.23\u20130.97,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.045). An interaction analysis demonstrated that the effect of MDRT differed according to PDRT status (HR 0.37, 95% CI: 0.22\u20130.57,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.008). The prolonged survival in the PDRT group remained significant in a time\u2010dependent multivariable Cox analysis (HR 0.47, 95% CI: 0.22\u20130.88,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.021).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We found significantly prolonged CRFS in the PDRT group compared with the non\u2010PDRT group among patients receiving upfront doublet therapy for high\u2010volume mHSPC. Interaction analysis also suggested that the effect of MDRT may differ according to PDRT status; however, these findings should be regarded as hypothesis\u2010generating. Further large prospective studies are needed to validate these findings in patients with high\u2010volume mHSPC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70238","type":"journal-article","created":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:35:41Z","timestamp":1787510141000},"page":"1489-1499","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic Impact of the Addition of Prostate\u2010Directed Radiotherapy With or Without Metastasis\u2010Directed Radiotherapy Under Upfront Doublet Therapy for High\u2010Volume Metastatic Hormone\u2010Sensitive Prostate Cancer"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8057-8221","authenticated-orcid":false,"given":"Dai","family":"Koguchi","sequence":"first","affiliation":[{"name":"Department of Urology Kitasato University School of Medicine Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8962-2345","authenticated-orcid":false,"given":"Hideyasu","family":"Tsumura","sequence":"additional","affiliation":[{"name":"Department of Urology Kitasato University School of Medicine Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken\u2010ichi","family":"Tabata","sequence":"additional","affiliation":[{"name":"Department of Urology Kitasato Institute Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takefumi","family":"Satoh","sequence":"additional","affiliation":[{"name":"Department of Urology Kitasato University School of Medicine Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Shiono","sequence":"additional","affiliation":[{"name":"Department of Urology Kitasato University School of Medicine Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6851-8665","authenticated-orcid":false,"given":"Shuhei","family":"Hirano","sequence":"additional","affiliation":[{"name":"Department of Urology Kitasato University School of Medicine Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1017-9799","authenticated-orcid":false,"given":"Masaomi","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Urology Kitasato University School of Medicine Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasufumi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Urology Sagmihara Kyodo Hospital Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0207-3270","authenticated-orcid":false,"given":"Kazuki","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Department of Urology International University of Health and Welfare Atami Hospital Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rena","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Urology Kitasato University Medical Center Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2966-6476","authenticated-orcid":false,"given":"Daisuke","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Urology Kitasato University School of Medicine Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7907-8422","authenticated-orcid":false,"given":"Hiromichi","family":"Ishiyama","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Kitasato University School of Medicine Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9465-5161","authenticated-orcid":false,"given":"Kazumasa","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Urology Kitasato University School of Medicine Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"American Urological Association. Advanced prostate cancer: AUA\/SUO guideline. Available online: (accessed on 27 Apr 2026).https:\/\/www.auanet.org\/guidelines-and-quality\/guidelines\/advanced-prostate-cancer."},{"key":"e_1_2_11_3_1","unstructured":"European Association of Urology. EAU\u2010EANM\u2010ESTRO\u2010ESUR\u2010ISUP\u2010SIOG guidelines on prostate cancer. Available online: (accessed on 27 Apr 2026).https:\/\/uroweb.org\/guidelines\/prostate-cancer\/chapter\/treatment."},{"key":"e_1_2_11_4_1","unstructured":"Japanese Urological Association [Internet]. JUA guidelines. Available online:https:\/\/www.urol.or.jp\/en(accessed on 27 Apr 2026)."},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2018.09.008"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1503747"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32486-3"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2023.113290"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2025.12.021"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01865-8"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1995.13.1.8"},{"key":"e_1_2_11_12_1","first-page":"417","article-title":"Enhanced Activated T Cell Subsets in Prostate Cancer Patients Receiving iodine\u2010125 Low\u2010Dose\u2010Rate Prostate Brachytherapy","volume":"39","author":"Kubo M.","year":"2018","journal-title":"Oncology Reports"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2004.01.020"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(87)90171-8"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19880101)61:1<195::AID-CNCR2820610133>3.0.CO;2-Y"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.4487"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23757"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.70152"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.70017"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2025.03.019"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-2340"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.115170"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23996"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/bjr\/tqae100"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14347"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18843-5"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.0147"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyaf157"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.70238","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pros.70238","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.70238","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:21:08Z","timestamp":1791804068000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.70238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,23]]},"references-count":27,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1002\/pros.70238"],"URL":"https:\/\/doi.org\/10.1002\/pros.70238","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,23]]},"assertion":[{"value":"2026-05-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}