{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T08:14:13Z","timestamp":1783152853794,"version":"3.54.6"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Astellas Pharma Inc, Pfizer Inc"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Prostate Cancer Prostatic Dis"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Limited real-world data exist on the effectiveness of treatment intensification (TI) with androgen receptor pathway inhibitors (ARPI) in de novo metastatic castration-sensitive prostate cancer (mCSPC). This study compared outcomes of TI or first-generation nonsteroidal antiandrogens (NSAAs) to androgen-deprivation therapy (ADT) alone in US patients with de novo mCSPC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Veterans Affairs patients with de novo mCSPC (February 2018\u2013June 2020) confirmed via chart review were grouped into ADT alone, ADT\u2009+\u2009NSAAs, or ADT\u2009+\u2009ARPI cohorts using predefined recruitment quotas. Outcomes included inverse probability of treatment weighting (IPTW)-adjusted overall survival (OS), progression to metastatic castration-resistant prostate cancer (mCRPC), and prostate-specific antigen (PSA) response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 384 patients were identified (ADT alone: 163, ADT\u2009+\u2009NSAA: 101, ADT\u2009+\u2009ARPI: 120). Median follow-up was 37.2, 38.1, and 34.8 months for ADT alone, ADT\u2009+\u2009NSAA, and ADT\u2009+\u2009ARPI, respectively. Compared with ADT alone, ADT\u2009+\u2009ARPI showed significantly better OS (HR [95% CI]: 0.61 [0.43 to 0.87],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007), lower risk of progression to mCRPC (0.46 [0.33 to 0.66],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and higher PSA response rate (PSA decline of \u226550% and \u226590% from baseline, and to &lt;0.2\u2009ng\/mL and &lt;0.1\u2009ng\/mL any time during first-line treatment; all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Outcomes with ADT\u2009+\u2009NSAA did not differ from ADT alone. ADT\u2009+\u2009ARPI was the most common second-line mCSPC and first-line mCRPC treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>First-line ADT\u2009+\u2009ARPI was associated with significantly improved outcomes vs ADT alone in de novo mCSPC. These real-world results align with the benefits demonstrated in trials, supporting integration of TI with ARPIs into clinical practice to improve survival outcomes in patients with de novo mCSPC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41391-025-01000-8","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T23:52:23Z","timestamp":1753401143000},"page":"167-174","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Survival benefit associated with first-line androgen receptor pathway inhibitors for de novo metastatic castration-sensitive prostate cancer"],"prefix":"10.1038","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8104-6419","authenticated-orcid":false,"given":"Stephen J.","family":"Freedland","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader","family":"El-Chaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3899-7702","authenticated-orcid":false,"given":"Amanda M.","family":"De Hoedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3636-5688","authenticated-orcid":false,"given":"Joshua A.","family":"Parrish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maelys","family":"Touya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0890-0268","authenticated-orcid":false,"given":"Krishnan","family":"Ramaswamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Polascik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"1000_CR1","first-page":"12","volume":"74","author":"RL Siegel","year":"2024","unstructured":"Siegel RL, Giaquinto AN, Jemal A. 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AH: received support for the present publication from Astellas Pharma; was a full-time employee of Astellas Pharma during the research period, and is currently employed at Pfizer; holds stock or other ownership interest at Pfizer. NE: received support for the present publication from Astellas Pharma; is a full-time employee of Astellas Pharma, and holds stocks or stock options with BNGO, RXRX, SNGX, and TNXP. AMD: received support for the present publication from Astellas Pharma (paid to institution); received grants or contracts from AstraZeneca, Blue Earth Diagnostics, Cedars-Sinai, Coloplast, Delfi Diagnostics, Exact Sciences, Ferring, Genomic Health, Guardant Health, Janssen, LungLife AI, Merck, Myovant Sciences, Myriad Genetics, Novartis, Pfizer, Photocure, Prostatype Genomics, Reinvestment Partners, University of California, Los Angeles, and VIR Biotechnology (all paid to institution). JK: is a full-time employee of Astellas Pharma. CE: Received support for the present manuscript from Astellas Pharma (paid to institution); received grants or contracts from AstraZeneca, Blue Earth Diagnostics, Cedars-Sinai, Coloplast, Delfi Diagnostics, Exact Sciences, Ferring, Genomic Health, Guardant Health, Janssen, LungLife AI, Merck, Myovant Sciences, Myriad Genetics, Novartis, Pfizer, Photocure, Prostatype Genomics, Reinvestment Partners, University of California, Los Angeles, and VIR Biotechnology (all paid to institution). JAP: received support for the present manuscript from Astellas Pharma (paid to institution); received grants or contracts from AstraZeneca, Blue Earth Diagnostics, Cedars-Sinai, Coloplast, Delfi Diagnostics, Exact Sciences, Ferring, Genomic Health, Guardant Health, Janssen, LungLife AI, Merck, Myovant Sciences, Myriad Genetics, Novartis, Pfizer, Photocure, Prostatype Genomics, Reinvestment Partners, University of California, Los Angeles, and VIR Biotechnology (all paid to institution). MT: is a full-time employee of Astellas Pharma. KR: is a full-time employee of Pfizer; received support for travel, accommodations and expenses from Pfizer; holds stock or other ownership interests with BMS, Johnson & Johnson, and Pfizer. LG: none to declare TJP: received support for the present manuscript from Astellas Pharma; is chair of the Board of Directors for the Focal Therapy Society (unpaid).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study received Institutional Review Board and Research and Development approval from the Durham VA Health Care System with waiver of informed consent (IRB#1827). This study was conducted in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}