{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:30:11Z","timestamp":1790605811451,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NAWA","award":["BPN\/WAL\/2023\/1\/00061"],"award-info":[{"award-number":["BPN\/WAL\/2023\/1\/00061"]}]},{"name":"NAWA","award":["S-2023-0006"],"award-info":[{"award-number":["S-2023-0006"]}]},{"name":"EUSP Scholarship of the European Association of Urology","award":["BPN\/WAL\/2023\/1\/00061"],"award-info":[{"award-number":["BPN\/WAL\/2023\/1\/00061"]}]},{"name":"EUSP Scholarship of the European Association of Urology","award":["S-2023-0006"],"award-info":[{"award-number":["S-2023-0006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Purpose: The addition of androgen receptor pathway inhibitors (ARPIs) to androgen deprivation therapy (ADT), with or without docetaxel (Doc), is currently recommended for metastatic, hormone-sensitive prostate cancer (mHSPC). Recently, the ARANOTE trial evaluated the efficacy and safety of Darolutamide + ADT in this setting. We aimed to update a network meta-analysis (NMA) of these combination therapies. Methods: We conducted a systematic search for RCTs on systemic therapies for mHSPC using MEDLINE, Embase, and the Web of Science Core Collection in September 2024. An NMA utilizing random-effects models was performed to compare progression-free survival (PFS), overall survival (OS), and adverse event (AE) incidence (PROSPERO: CRD42024591458). Results: A total of 12 RCTs (n = 11,954) were included in our NMAs. Triplet therapies were associated with significant improvements in PFS compared to ARPI-based doublet therapies (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.59\u20130.93; p = 0.01), but the difference did not reach the conventional levels of statistical significance for OS (HR: 0.82; 95% CI: 0.67\u20131.01; p = 0.059). In a subset analysis, compared to ARPI-based doublet therapies, triplet therapies showed a significant improvement in PFS in patients with high-volume disease (HR: 0.64; 95% CI: 0.47\u20130.88; p &lt; 0.01), whereas no significant improvement was observed in those with low-volume disease (HR: 0.86; 95% CI: 0.45\u20131.67; p = 0.7). No significant difference in grade \u2265 3 AEs was observed between triplet therapies and ARPI-based doublet therapies. The main limitations include patient heterogeneity and limited follow-up in some studies. Conclusions: Triplet therapies can improve the oncologic outcomes of patients with mHSPC compared to ARPI-based doublet therapies, without significantly increasing severe AEs. These findings warrant further confirmation in a head-to-head trial powered for overall survival.<\/jats:p>","DOI":"10.3390\/cancers17020205","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T03:48:11Z","timestamp":1736480891000},"page":"205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["An Updated Systematic Review and Network Meta-Analysis of First-Line Triplet vs. Doublet Therapies for Metastatic Hormone-Sensitive Prostate Cancer"],"prefix":"10.3390","volume":"17","author":[{"given":"Akihiro","family":"Matsukawa","sequence":"first","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Urology, The Jikei University School of Medicine, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8368-2513","authenticated-orcid":false,"given":"Giulio","family":"Litterio","sequence":"additional","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Medical, Oral and Biotechnological Sciences, G. d\u2019Annunzio University of Chieti, 66013 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Cormio","sequence":"additional","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Urology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Di Ancona, Universit\u00e0 Politecnica Delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4375-0827","authenticated-orcid":false,"given":"Marcin","family":"Miszczyk","sequence":"additional","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Collegium Medicum\u2014Faculty of Medicine, WSB University, 41-300 D\u0105browa G\u00f3rnicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9380-8492","authenticated-orcid":false,"given":"Mehdi","family":"Kardoust Parizi","sequence":"additional","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Fazekas","sequence":"additional","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Urology, Semmelweis University, 1082 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Tsuboi","sequence":"additional","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Urology, Shimane University Faculty of Medicine, Izumo 693-8504, Shimane, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8209-9379","authenticated-orcid":false,"given":"Stefano","family":"Mancon","sequence":"additional","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy"},{"name":"Department of Urology, IRCCS Humanitas Research Hospital, 20090 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Schulz","sequence":"additional","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Urology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Laukhtina","sequence":"additional","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Rajwa","sequence":"additional","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Second Department of Urology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland"},{"name":"Division of Surgery and Interventional Science, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichiro","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Urology, The Jikei University School of Medicine, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2911-7627","authenticated-orcid":false,"given":"Piotr","family":"Chlosta","sequence":"additional","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Urology, Medical College, Jagiellonian University, 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1702-4127","authenticated-orcid":false,"given":"Michele","family":"Marchioni","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral and Biotechnological Sciences, G. d\u2019Annunzio University of Chieti, 66013 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Schips","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral and Biotechnological Sciences, G. d\u2019Annunzio University of Chieti, 66013 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Miki","sequence":"additional","affiliation":[{"name":"Department of Urology, The Jikei University School of Medicine, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5673-1553","authenticated-orcid":false,"given":"Takahiro","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Urology, The Jikei University School of Medicine, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrokh F.","family":"Shariat","sequence":"additional","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Urology, Semmelweis University, 1082 Budapest, Hungary"},{"name":"Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"},{"name":"Department of Urology, Weill Cornell Medical College, New York, NY 10065, USA"},{"name":"Department of Urology, Second Faculty of Medicine, Charles University, 15006 Prague, Czech Republic"},{"name":"Division of Urology, Department of Special Surgery, The University of Jordan, Amman 11942, Jordan"},{"name":"Karl Landsteiner Institute of Urology and Andrology, 1010 Vienna, Austria"},{"name":"Research Center for Evidence Medicine, Urology Department, Tabriz University of Medical Sciences, Tabriz 51656-65811, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Yanagisawa","sequence":"additional","affiliation":[{"name":"Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Urology, The Jikei University School of Medicine, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1097\/JU.0000000000003452","article-title":"Updates to Advanced Prostate Cancer: AUA\/SUO Guideline 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Cancer"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/2\/205\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:26:06Z","timestamp":1759919166000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/2\/205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,9]]},"references-count":40,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["cancers17020205"],"URL":"https:\/\/doi.org\/10.3390\/cancers17020205","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,9]]}}}