{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T22:47:55Z","timestamp":1776638875476,"version":"3.51.2"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study evaluates the impact of early modification of upfront androgen receptor signaling inhibitors (ARSI) on outcomes among patients with metastatic hormone\u2010sensitive prostate cancer (mHSPC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective, multicenter cohort study included 590 patients with mHSPC who received upfront ARSI combined with androgen deprivation therapy. All had a follow\u2010up duration of \u2265\u20096 months. The impact of early modification of ARSI without progression on survival outcomes was analyzed. The inverse probability of treatment weighting (IPTW) was applied to adjust for confounding factors associated with survival outcomes, comparing patients who did and did not discontinue ARSI early.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Upfront abiraterone acetate, apalutamide, and enzalutamide were used in 50.8%, 28.1%, and 21.0% of patients, respectively. The rates of withdrawal of the upfront ARSI and initial dose reduction were 21.2% and 6.1%, respectively. The highest withdrawal rate (33.1%) was with apalutamide, mainly due to adverse events (89.1%). Apalutamide use (odds ratio [OR] 2.39, 95% CI: 1.50\u20133.80) and a low\u2010risk CHAARTED status (OR 1.84, 95% CI: 1.08\u20133.14) were identified as independent risk factors for early ARSI withdrawal. IPTW analysis revealed early ARSI withdrawal (within 6 months) significantly correlated with poor castration\u2010resistant prostate cancer\u2010free survival (CRPC\u2010FS) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004) and second progression\u2010free survival (PFS2) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.035). However, it had no significant relationship with overall survival (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.280).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Early withdrawal of initial upfront ARSI was associated with poor CRPC\u2010FS and PFS2 among mHSPC patients. Maximizing the effectiveness of first\u2010line treatment requires optimal management of ARSI therapy.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      jRCTs021180021.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70092","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:20:31Z","timestamp":1762420831000},"page":"357-364","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Impact of Early Modification of Upfront Androgen Receptor Signaling Inhibitors on Survival Outcomes in Metastatic Hormone\u2010Sensitive Prostate Cancer"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2988-1860","authenticated-orcid":false,"given":"Shintaro","family":"Narita","sequence":"first","affiliation":[{"name":"Department of Urology Akita University Graduate School of Medicine Akita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7410-0712","authenticated-orcid":false,"given":"Takafumi","family":"Yanagisawa","sequence":"additional","affiliation":[{"name":"Department of Urology The Jikei University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Hatakeyama","sequence":"additional","affiliation":[{"name":"Department of Urology Hirosaki University Graduate School of Medicine Hirosaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1044-912X","authenticated-orcid":false,"given":"Wataru","family":"Fukuokaya","sequence":"additional","affiliation":[{"name":"Department of Urology The Jikei University School of Medicine Tokyo 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Graduate School of Medicine Akita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3946-3788","authenticated-orcid":false,"given":"Shuhei","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Urology Akita University Graduate School of Medicine Akita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soki","family":"Kashima","sequence":"additional","affiliation":[{"name":"Department of Urology Akita University Graduate School of Medicine Akita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryohei","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Urology Akita University Graduate School of Medicine Akita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mizuki","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Urology Akita University Graduate School of Medicine Akita 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Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomonori","family":"Habuchi","sequence":"additional","affiliation":[{"name":"Department of Urology Akita University Graduate School of Medicine Akita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"JHA\u2010Upfront Study 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