{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:53:45Z","timestamp":1791251625846,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473381"],"award-info":[{"award-number":["82473381"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess whether treatment\u2010period serum testosterone breakthrough &gt;35\u2009ng\/dL is associated with clinical outcomes during intensified therapy for metastatic hormone\u2010sensitive prostate cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>\n                      We performed\n                      <jats:italic>post hoc<\/jats:italic>\n                      analyses of the experimental arms of the ARASENS (darolutamide plus androgen deprivation therapy [ADT] and docetaxel; ClinicalTrials.gov identifier NCT02799602) and LATITUDE (abiraterone acetate plus prednisone and ADT; NCT01715285) phase III trials. Cohort\u2010specific fixed\u2010window landmark analyses classified exposure as any eligible testosterone result &gt;35\u2009ng\/dL after treatment initiation and through Day 147 in the LATITUDE trial or Day 266 in the ARASENS trial. Treatment\u2010initiation\/Day\u20101 and end\u2010of\u2010treatment measurements were excluded. Follow\u2010up began at the landmark. The primary outcome was overall survival (OS); the LATITUDE progression\u2010free survival (PFS) and the ARASENS time to castration\u2010resistant prostate cancer (CRPC) were progression endpoints. Multivariable Cox regression was primary; landmark and time\u2010dependent sensitivity analyses were also performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At the landmark, 564 LATITUDE and 578 ARASENS patients were classifiable for OS. In the LATITUDE trial, breakthrough was associated with worse OS (adjusted hazard ratio [HR], 1.49, 95% confidence interval [CI] 1.07\u20132.08;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.019); the PFS estimate was directionally similar but imprecise (HR 1.40, 95% CI 0.98\u20132.00;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.065). In the ARASENS trial, the overall associations were not statistically significant for OS (HR 1.18, 95% CI 0.85\u20131.62;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.322) or CRPC (HR 0.86, 95% CI, 0.60\u20131.23;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.397). Exploratory piecewise modelling suggested time variation for CRPC (interaction\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.028).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Testosterone breakthrough &gt;35\u2009ng\/dL was associated with worse post\u2010landmark OS in the LATITUDE trial, whereas the overall associations with OS and CRPC in the ARASENS trial were not statistically significant. These within\u2010cohort findings are exploratory and do not establish causality, a difference between treatment mechanisms, or a clinical testosterone target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bju.70474","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:21:29Z","timestamp":1791249689000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Testosterone breakthrough and outcomes during intensified therapy in metastatic hormone\u2010sensitive prostate cancer: the\n                    <scp>ARASENS<\/scp>\n                    and\n                    <scp>LATITUDE trials<\/scp>"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5257-7651","authenticated-orcid":false,"given":"Xiyue","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"},{"name":"Shanghai Genitourinary Cancer Institute  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3131-8964","authenticated-orcid":false,"given":"Xudong","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"},{"name":"Shanghai Genitourinary Cancer Institute  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"},{"name":"Shanghai Genitourinary Cancer Institute  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"},{"name":"Shanghai Genitourinary Cancer Institute  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"},{"name":"Shanghai Genitourinary Cancer Institute  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9687-1435","authenticated-orcid":false,"given":"Hongkai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"},{"name":"Shanghai Genitourinary Cancer Institute  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingwei","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"},{"name":"Shanghai Genitourinary Cancer Institute  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4125-7975","authenticated-orcid":false,"given":"Junlong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"},{"name":"Shanghai Genitourinary Cancer Institute  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7950-6669","authenticated-orcid":false,"given":"Yao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology, Shanghai Medical College Fudan University  Shanghai China"},{"name":"Shanghai Genitourinary Cancer Institute  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"232","article-title":"Studies on prostatic cancer. 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