{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:41:31Z","timestamp":1789620091279,"version":"build-2803163510"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Prostate Cancer Prostatic Dis"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Enzalutamide (ENZA), a next-generation non-steroidal androgen receptor (AR) inhibitor, plays a pivotal role in the management of both hormone-sensitive (HSPC) and androgen deprivation-resistant prostate cancer (ARPC). This paper presents real-world clinical outcomes of ENZA in a subgroup of metastatic HSPC (mHSPC) patients included in the ARON-3 study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical information was extracted retrospectively from medical records at 29 cancer centres in 9 countries worldwide. Overall Survival (OS) was calculated from starting ENZA to death from any cause and the time on treatment (ToT) from ENZA initiation to discontinuation for any reason. The Kaplan\u2013Meier method was used to estimate OS and ToT. PSA90 was defined as a \u226590% PSA reduction from baseline, and PSA0.2 as the achievement of an ultra-low PSA level \u22640.2\u2009ng\/ml. Adverse events (AEs) were categorised according to Common Terminology Criteria for Adverse Events v5.0.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The study population comprised 424 patients treated with ENZA for mHSPC, of whom 80 (19%) had lymph node-only metastases, 265 (63%) bone-only metastases, and 50 (12%) visceral metastases. 273 patients (64%) had synchronous metastases and 151 (36%) had developed metachronous metastases. A total of 228 patients were diagnosed with low-volume disease, and 196 patients (46%) with high-volume disease. The median ToT was 31.8 months, and the median OS was not reached. The median time to PSA90 (achieved in 76% of patients) and PSA0.2 (59% of patients) was 6.0 months and 8.3 months, respectively. Statistically significant associations were identified between lymph node-only patterns, PSA90 and ultra-low PSA responses, and longer treatment duration and better overall survival. Grade 3\u20134 AEs were observed in 9% of patients &lt;70 years and in 10% \u226570 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Real-world clinical practice corroborates the findings from clinical trials, confirming the effectiveness and safety of ENZA in mHSPC patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41391-025-01067-3","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:09:47Z","timestamp":1767830987000},"page":"588-594","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Enzalutamide in metastatic hormone-sensitive prostate cancer: results from the international, multicentre, real-world ARON-3 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MR has received honoraria as a speaker\/consultant by MSD, Merck Serono, Astrazeneca, Bristol Myers Squibb, Eisai and Gilead. LBV has received payments or honoraria from presentations, consulting or travel expenses from J&J, Bayer, Ipsen, Pfizer, MSD, BMS, Astellas, AstraZeneca, Tecnofarma, Merck. AJ reports payments or honoraria from presentations, speaker bureaus, consulting or travel expenses from J&J, Orion, Bayer, Astellas, Ipsen, Pfizer, BMS. JM-C declares consultant, advisory or speaker roles for IPSEN, Roche, Pfizer, Sanofi, Janssen, BMS, Exelisis, MSD, Adium, Astellas. JMC has received research grants from Pfizer, IPSEN, Janssen and Roche. TB has received institutional research support from AstraZeneca, Roche, Bristol Myers Squibb, Exelixis, Merck, and Novartis; consulting fees from Bristol Myers Squibb, Astellas, Janssen, and Sanofi\/Aventis; payment or honoraria for lectures, presentations, speakers\u2019 bureaus, manuscript writing, or educational events from Ipsen, Bristol Myers Squibb, Servier, and Pfizer; and institutional receipt of equipment, materials, drugs, medical writing, or other services from Bristol Myers Squibb, AstraZeneca, Roche, and Servier. JK has received payment or honoraria for consultations, lectures or educational events: Angelini, Astellas, Astra Zeneca, Bayer, Bristol Myers Squibb, IPSEN, Johnson&Johnson, Merck, MSD, Novartis, Pfizer, Research Funding: Novartis. MNGQ has received payments or honoraria from presentations, speaker bureaus, consulting, or travel expenses from Bayer, Astellas, Novartis, MSD, Merck Serono, Adium, Pfizer, Gador, and Elea. MTB has received payments or honoraria from presentations, speaker bureaus, consulting, or travel expenses from Bayer, Astellas, Novartis, MSD, Merck Serono, Adium, Pfizer, Johson & Johson, Asofarma Astra Zeneca. PR reports payments or honoraria for advisory board roles, presentations, speaker bureaus, manuscript writing, educational events, or travel support from AstraZeneca, Janssen, Pfizer, Merck, MSD Italy. OF received honoraria from Roche, Janssen, GSK, MSD, BMS, Pierre Fabre and Pfizer for consultations and lectures. Alejo Rodriguez-Vida reports serving in an advisory role for Pfizer, BMS, Merck, MSD, Astellas, Janssen, Bayer, Novartis and Ipsen; receiving honoraria or travel expenses from Pfizer, MSD, Astellas, Merck, BMS, Janssen, Astra Zeneca, Bayer, and Ipsen. Y\u00dc has received honoraria or has served as consultant for Abdi-\u0130brahim, Astellas, Bristol Myers-Squibb, Deva, Eczac\u0131ba\u015f\u0131, Gen \u0130la\u00e7, Gilead, GSK, Janssen, Merck, Novartis, Pfizer, Roche. SS has received payments or honoraria from presentations, speaker bureaus, consulting or travel expenses from J&J, Bayer, Astellas, Novartis, Ipsen, MSD, BMS, Merck Serono. AP reports payments or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from BMS, Ipsen, Roche, Astellas, Merck, Eisai, MSD, Novartis, and Pfizer. DM has received honoraria for educational sessions from Astellas, Bayer and Janssen. AM has received payments or honoraria from presentations, consulting or travel expenses from Ipsen, MSD, Bayer, J&J, BMS. BM has received research funding, honoraria, and non-financial or other support from Roche, Pfizer, BMS, Astellas, Novartis, MSD, Merck Serono, AstraZeneca, Eisai, and E. Lilly. MW reports payments or honoraria from presentations, speaker bureaus, consulting or travel expenses from J&J, Bayer, Accord, Ipsen, AstraZeneca, Pfizer, MSD. PM reports payments or honoraria from presentations, speaker bureaus, consulting or travel expenses from J&J, Novartis, Orion, Bayer, Astellas, Ipsen, Amgen, AstraZeneca, Pfizer, MSD. FM has received research support and\/or honoraria from Advanced Accelerator Applications, Astellas, Astra Zeneca, Bayer, BMS, Janssen, Ipsen, MSD and Pfizer. ESA has received grants and personal fees from Janssen, Sanofi, Bayer, Bristol Myers Squibb, Curium, MacroGenics, Merck, Pfizer, AstraZeneca, and Clovis; personal fees from Aadi Bioscience, Aikido Pharma, Astellas, Amgen, Blue Earth, Corcept Therapeutics, Exact Sciences, Hookipa Pharma, In-vitae, Eli Lilly, Foundation Medicine, Menarini-Silicon Biosystems, Tango Therapeutics, Tempus and Z-alpha; grants from Novartis, Celgene, and Orion; and has a patent for an AR-V7 biomarker technology that has been licensed to Qiagen. MS has received research support and honoraria from Janssen, Bristol Myers Squibb, Ipsen, MSD, Astellas and Bayer. The other authors declare to have no conflicts of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The protocol was approved on 18 April 2024 by the Ethics Committee of the coordinating centre (Marche Region - Italy - No. 2024 20, \u2018ARON-3 Study\u2019 protocol) and the Institutional Review Boards of each participating site. The study was conducted in accordance with the Declaration of Helsinki on human experimentation and Good Clinical Practice standards. Informed consent with subsequent analysis of the follow-up data was obtained from all participants.","order":2,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Ethics"}}]}}