{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T10:17:22Z","timestamp":1788603442545,"version":"build-2803163510"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Prostate Cancer Prostatic Dis"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1038\/s41391-025-01047-7","type":"journal-article","created":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T11:33:16Z","timestamp":1761996796000},"page":"642-645","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["DARolutamide ObservationaL (DAROL) study in patients with nonmetastatic castration-resistant prostate cancer: prespecified third interim analysis"],"prefix":"10.1038","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1510-8044","authenticated-orcid":false,"given":"Evan Y.","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyoshi","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2531-7587","authenticated-orcid":false,"given":"Christopher M.","family":"Pieczonka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"Gotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Briganti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0575-5635","authenticated-orcid":false,"given":"Murilo","family":"Luz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7500-5899","authenticated-orcid":false,"given":"Declan","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Malone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan E.","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Sieber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Given","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Hellmis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kretz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Spiegelhalder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9773-4590","authenticated-orcid":false,"given":"Antonio","family":"G\u00f3mez-Caama\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaovi Messan","family":"Amela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Artignan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroji","family":"Uemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Adorjan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedeh","family":"Ghadessi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Verholen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7012-1754","authenticated-orcid":false,"given":"Andrew J.","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,1]]},"reference":[{"key":"1047_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/srep12007","volume":"5","author":"AM Moilanen","year":"2015","unstructured":"Moilanen AM, Riikonen R, Oksala R, Ravanti L, Aho E, Wohlfahrt G, et al. Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies. Sci Rep. 2015;5:12007.","journal-title":"Sci Rep"},{"key":"1047_CR2","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1200\/JCO.2018.36.6_suppl.345","volume":"36","author":"C Zurth","year":"2018","unstructured":"Zurth C, Sandmann S, Trummel D, Seidel D, Gieschen H. Blood-brain barrier penetration of [14C] darolutamide compared with [14C] enzalutamide in rats using whole body autoradiography. J Clin Oncol. 2018;36:345.","journal-title":"J Clin Oncol"},{"key":"1047_CR3","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1007\/s13318-019-00577-5","volume":"44","author":"C Zurth","year":"2019","unstructured":"Zurth C, Koskinen M, Fricke R, Prien O, Korjamo T, Graudenz K, et al. Drug-drug interaction potential of darolutamide: in vitro and clinical studies. Eur J Drug Metab Pharmacokinet. 2019;44:747\u201359.","journal-title":"Eur J Drug Metab Pharmacokinet"},{"key":"1047_CR4","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1007\/s11523-019-00674-0","volume":"14","author":"N Shore","year":"2019","unstructured":"Shore N, Zurth C, Fricke R, Gieschen H, Graudenz K, Koskinen M, et al. Evaluation of clinically relevant drug-drug interactions and population pharmacokinetics of darolutamide in patients with nonmetastatic castration-resistant prostate cancer: Results of pre-specified and post hoc analyses of the phase III ARAMIS trial. Target Oncol. 2019;14:527\u201339.","journal-title":"Target Oncol"},{"key":"1047_CR5","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1007\/s11523-023-00959-5","volume":"18","author":"SCR Williams","year":"2023","unstructured":"Williams SCR, Mazibuko N, O\u2019Daly O, Zurth C, Patrick F, Kappeler C, et al. Comparison of cerebral blood flow in regions relevant to cognition after enzalutamide, darolutamide, and placebo in healthy volunteers: A randomized crossover trial. Target Oncol. 2023;18:403\u201313.","journal-title":"Target Oncol"},{"key":"1047_CR6","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1056\/NEJMoa1815671","volume":"380","author":"K Fizazi","year":"2019","unstructured":"Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019;380:1235\u201346.","journal-title":"N Engl J Med"},{"key":"1047_CR7","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1056\/NEJMoa2001342","volume":"383","author":"K Fizazi","year":"2020","unstructured":"Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, et al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med. 2020;383:1040\u20139.","journal-title":"N Engl J Med"},{"key":"1047_CR8","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1056\/NEJMoa2119115","volume":"386","author":"MR Smith","year":"2022","unstructured":"Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022;386:1132\u201342.","journal-title":"N Engl J Med"},{"key":"1047_CR9","doi-asserted-by":"publisher","first-page":"4271","DOI":"10.1200\/JCO-24-01798","volume":"42","author":"F Saad","year":"2024","unstructured":"Saad F, Vjaters E, Shore N, Olmos D, Xing N, Pereira de Santana Gomes AJ, et al. Darolutamide in combination with androgen-deprivation therapy in patients with metastatic hormone-sensitive prostate cancer from the phase III ARANOTE trial. J Clin Oncol. 2024;42:4271\u201381.","journal-title":"J Clin Oncol"},{"key":"1047_CR10","doi-asserted-by":"publisher","first-page":"e2429783","DOI":"10.1001\/jamanetworkopen.2024.29783","volume":"7","author":"DJ George","year":"2024","unstructured":"George DJ, Morgans AK, Constantinovici N, Khan N, Khan J, Chen G, et al. Androgen receptor inhibitors in patients with nonmetastatic castration-resistant prostate cancer. JAMA Open Netw. 2024;7:e2429783.","journal-title":"JAMA Open Netw"}],"container-title":["Prostate Cancer and Prostatic Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41391-025-01047-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41391-025-01047-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41391-025-01047-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:02:36Z","timestamp":1786701756000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41391-025-01047-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,1]]},"references-count":10,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["1047"],"URL":"https:\/\/doi.org\/10.1038\/s41391-025-01047-7","relation":{},"ISSN":["1365-7852","1476-5608"],"issn-type":[{"value":"1365-7852","type":"print"},{"value":"1476-5608","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,1]]},"assertion":[{"value":"11 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 November 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"EYY certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (e.g., employment\/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patients filed, received, or pending), are the following: the DAROL\u00a0study was sponsored by Bayer, which also funded medical writing and editorial support in the development of this manuscript; EYY has received consulting fees from Johnson & Johnson, Bayer, Merck, Advanced Accelerator Applications\/Novartis, AstraZeneca, Oncternal Therapeutics, Tolmar, Bristol-Myers Squibb, Loxo\/Lilly, Aadi Bioscience, and Lantheus, and research funding paid to his institution from Dendreon, Merck, Seagen\/Pfizer, Blue Earth Diagnostics, Bayer, Lantheus Medical Imaging, Tyra Biosciences, and Oncternal Therapeutics; HS has received fees and payment or honoraria from Janssen Research & Development, AstraZeneca, Astellas Pharma, Bayer Yakuhin, Bayer, Janssen Oncology, Pfizer, Takeda, Sanofi, Nippon Shinyaku, Daiichi Sankyo, Novartis, Kissei Pharmaceutical, and Merck Biopharma, and research funding paid to his institution from AstraZeneca, Astellas Pharma, Janssen, Nihon Kayaku, and Bayer Yakuhin; CMP has received fees from Pfizer\/Astellas, Bayer, Janssen Oncology, Tolmar, Sun Pharma, Dendreon, AstraZeneca, Merck, Bristol-Myers Squibb, and Novartis, payment or honoraria from Bayer, Dendreon, Pfizer, Astellas Pharma, Sun Pharma, Myovant Sciences, Janssen Oncology, AstraZeneca, Merck, Bristol-Myers Squibb, and Novartis, has held leadership or fiduciary roles and stock in Associated Medical Professionals of New York and US Urology Partners, and has received research funding from Bayer, Pfizer, Astellas Pharma, Merck, AstraZeneca, Advantagene, Dendreon, Janssen Oncology, and InVitae; GG has received fees and honoraria from Janssen, Astellas Pharma, Bayer, Merck, AstraZeneca, Ferring, Pfizer, Tolmar, McKesson, EMD Serono, Bristol-Myers Squibb, and Sanofi, support for attending meetings and\/or travel from Janssen and Pfizer, and research funding from Janssen; AB has received fees and honoraria from Astellas Pharma, Janssen-Cilag, OPKO Health, MDxHealth, Ferring, Bayer, AstraZeneca, Hauora, and Pfizer, and research funding from Sandoz-Novartis and Merck Sharp & Dohme; ML has received fees and payment or honoraria from Bayer, Janssen, and Astellas Pharma, support for attending meetings and\/or travel from Bayer, Janssen, Astellas Pharma, Roche, and Merck, and research funding from Janssen, Bayer, Pfizer, Medivation, Myovant Sciences, and Roche\/Genentech; DM has received fees and\/or honoraria from Astellas Pharma, Janssen Oncology, Bayer Schering Pharma, AstraZeneca, Bayer, Ferring, Ipsen, and Novartis, and support for attending meetings and\/or travel from Device Technologies; RM has received payment or honoraria from Dendreon and Johnson & Johnson, participated on a data safety monitoring board or advisory board for Novartis, Ferring, AstraZeneca, Caris, Dendreon, and Telix, and has held a leadership or fiduciary role in Indiana Urologic Society; JH has consultancy agreements with Bayer HealthCare Pharmaceuticals, Johnson & Johnson, Dendreon, and Pfizer; JEC has received payment or honoraria from Boston Scientific Corporation, Bayer, Janssen (Johnson & Johnson), Laborie Medical Technologies, Tolmar, Tersera, and Angiodynamics, support for attending meetings and\/or travel from Angiodynamics, Janssen, Tolmar, Tersera, and Laborie Medical Technologies, and has participated on data safety monitoring boards or advisory boards for Janssen, Tolmar, Tersera, and Bayer; PS has received consulting fees from Pfizer, Accord, and Verity, payment or honoraria for speakers\u2019 bureau for Astellas, Bayer, Dendreon, Janssen, Merck, Myovant, and Pfizer, and research funding from Astellas, AstraZeneca, Bayer, Dendreon, Janssen, Merck, Myovant, Orion, and Pfizer; RWG has received payment or honoraria from Janssen, Bayer, and Myovant, and support for attending meetings and\/or travel from Francis Medical; EH has received consulting fees from Johnson & Johnson, Ipsen, Bristol-Myers Squibb, Roche, Takeda, AstraZeneca, Bayer Vital, Pfizer, Eisai, Merck Sharp & Dohme, Hexal, Merck, Apogepha, Astellas, Novartis, Merck, Orion, and Accord, payment or honoraria from Johnson & Johnson, Ipsen, Bristol-Myers Squibb, Roche, Takeda, AstraZeneca, Bayer Vital, Eisai, Apogepha, Pfizer, Merck Sharp & Dohme, Hexal, and Merck, support for attending meetings and\/or travel from Bayer HealthCare, Johnson & Johnson, Pfizer, and AstraZeneca, and has participated on data safety monitoring boards or advisory boards for Johnson & Johnson, Bayer HealthCare, AstraZeneca, and Pfizer; AGC has received payment or honoraria and support for attending meetings or travel from Astellas, Bayer, and Janssen; HU has received payment or honoraria from Pfizer, Bayer, AstraZeneca, Ferring Pharma, and Takeda, and has participated on a data safety monitoring board or advisory board for Janssen; PA, MG, and FV are employees of Bayer; AJA has received consulting fees from Astellas Scientific and Medical Affairs Inc, AstraZeneca, Bayer, Bristol-Myers Squibb, Epic Sciences, Exelixis, FORMA Therapeutics, GoodRx, IDEAYA Biosciences, Janssen, Merck, Myovant Sciences, Novartis, and Pfizer, support for attending meetings and\/or travel from Astellas Scientific and Medical Affairs Inc., and research funding to his institution from Amgen, Astellas Pharma, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Constellation Pharmaceuticals, Dendreon, FORMA Therapeutics, Gilead Sciences, Janssen Oncology, Merck, Novartis, Pfizer, and Roche\/Genentech; all other authors report no additional conflicts of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}