{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T20:19:06Z","timestamp":1788553146942,"version":"build-2803163510"},"reference-count":11,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"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":["Int J of Urology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background and Objective<\/jats:title>\n The PEACE\u20103 trial demonstrated overall survival benefit for enzalutamide plus radium\u2010223 versus enzalutamide alone in metastatic castration\u2010resistant prostate cancer (mCRPC), but survival curves showed initial crossing followed by progressive separation, indicating non\u2010proportional hazards. We aimed to characterize the time\u2010dependent treatment effects through comprehensive analysis.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Individual patient datas (IPD) were reconstructed from published Kaplan\u2013Meier curves of the PEACE\u20103 trial. Time\u2010dependent treatment effects were evaluated by restricted mean survival time (RMST) analysis at predefined time points (18\u201372\u2009months), time\u2010dependent Cox regression with treatment\u2010by\u2010time interaction, piecewise Cox regression across 6 time intervals, landmark analyses, and Fleming\u2010Harrington weighted log\u2010rank tests.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 446 IPDs were reconstructed. Validation confirmed consistency with the original trial. During the initial 18\u2009months, combination therapy showed no survival advantage (RMST difference: \u22120.36\u2009months, 95% CI, \u22120.90 to 0.18,\n p<\/jats:italic>\n \u2009=\u20090.20) and was associated with increased hazard (HR\u2009=\u20092.14, 95% CI, 1.48\u20133.10,\n p<\/jats:italic>\n \u2009<\u20090.001). Significant survival benefits were observed after 60\u2009months, with RMST differences of 4.34\u2009months (95% CI, 0.49\u20138.19,\n p<\/jats:italic>\n \u2009=\u20090.03) at 60\u2009months and 6.25\u2009months (95% CI, 1.56\u201310.95,\n p<\/jats:italic>\n \u2009=\u20090.01) at 72\u2009months. Time\u2010dependent Cox regression confirmed a significant treatment\u2010by\u2010time interaction (\n p<\/jats:italic>\n \u2009<\u20090.01). Piecewise analysis revealed the most substantial benefit for 60\u201372\u2009months (HR\u2009=\u20090.20, 95% CI, 0.05\u20130.77,\n p<\/jats:italic>\n \u2009=\u20090.02). Landmark analyses consistently demonstrated increasing treatment benefit with longer follow\u2010up.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Enzalutamide plus radium\u2010223 demonstrates delayed but substantial survival benefit in mCRPC, becoming statistically significant after 60\u2009months with over 6\u2009months survival advantage at 72\u2009months.<\/jats:p>\n <\/jats:sec>\n \n Registry and the Registration No. of the Study\/Trial<\/jats:title>\n Not applicable.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/iju.70376","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T11:55:47Z","timestamp":1770638147000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Delayed Survival Benefit of Enzalutamide Plus Radium\u2010223 in Metastatic Castration\u2010Resistant Prostate Cancer: A Time\u2010Dependent Analysis of Reconstructed Individual Patient Data From the\n PEACE<\/scp>\n \u20103 Trial"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2275-4527","authenticated-orcid":false,"given":"Wei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Urology Institute of Science Tokyo Tokyo Japan"},{"name":"Department of Urology Zigong Fourth People\u2018s Hospital Zigong Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2757-8083","authenticated-orcid":false,"given":"Soichiro","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Urology Institute of Science Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2300-8446","authenticated-orcid":false,"given":"Shugo","family":"Yajima","sequence":"additional","affiliation":[{"name":"Department of Urology National Cancer Center Hospital East Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4122-5279","authenticated-orcid":false,"given":"Kenji","family":"Tanabe","sequence":"additional","affiliation":[{"name":"Department of Urology Institute of Science Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9454-3345","authenticated-orcid":false,"given":"Motohiro","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Urology Teikyo University Hospital Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7548-1580","authenticated-orcid":false,"given":"Hiroshi","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Department of Urology Institute of Science Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3632-2901","authenticated-orcid":false,"given":"Hajime","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Urology Institute of Science Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Hirakawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Biostatistics Institute of Science Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Urology National Cancer Center Hospital East Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6761-3229","authenticated-orcid":false,"given":"Yasuhisa","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Urology Institute of Science Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.20517\/cdr.2024.173"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010022\u201005084\u20101"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(14)70474\u20107"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.05.011"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12874\u2010025\u201002608\u2010z"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.15657"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12874\u2010021\u201001308\u20108"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20163899"},{"issue":"4","key":"e_1_2_11_10_1","first-page":"330","article-title":"Alpha Particles as Radiopharmaceuticals in the Treatment of Bone Metastases: Mechanism of Action of Radium\u2010223 Chloride (Alpharadin) and Radiation Protection","volume":"26","author":"Cheetham P. 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