{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T10:19:50Z","timestamp":1777889990214,"version":"3.51.4"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"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":[{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Oncol. Rev."],"abstract":"<jats:p>This article aims to critically evaluate the evidence for triplet therapy consisting of androgen deprivation therapy (ADT), docetaxel and a second-generation androgen receptor pathway inhibitor ([ARPI]; abiraterone, enzalutamide, darolutamide or apalutamide) in patients with metastatic hormone-sensitive prostate cancer (mHSPC), and what this evidence reveals regarding the use of these treatments in clinical practice. A search of PubMed, Medline, Embase, Cochrane, Scopus and Web of Science was conducted in April 2024 to identify relevant prospective and retrospective observational trials, randomized controlled trials (RCTs) and meta-analyses. The search identified 52 relevant articles: six full articles and 31 abstracts based on three RCTs, one observational study and 14 meta-analyses. Abiraterone- or darolutamide-containing triplet therapy was significantly better than ADT + docetaxel for improving overall survival in all study populations, particularly subgroups with high-volume and\/or synchronous disease. The tolerability of ADT + docetaxel and triplet therapy were similar with most adverse events related to docetaxel. There were no data comparing triplet therapy with ADT + ARPI doublet therapy. Triplet therapy appears to be the most effective first-line regimen for men with mHSPC, good performance status and high-volume and synchronous metastases. Darolutamide-based triplet therapy may also be of benefit in other patients with high- or low-risk disease. Careful consideration of the risks and benefits are required to determine which patients can be spared from receiving docetaxel and rather be treated with alternative regimens.<\/jats:p>","DOI":"10.3389\/or.2025.1599292","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T06:06:28Z","timestamp":1753423588000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Triplet systemic therapy for hormone-sensitive prostate cancer: a critical review with a multidisciplinary approach"],"prefix":"10.3389","volume":"19","author":[{"given":"Almudena","family":"Zapatero","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Alonso-Gordoa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Rodr\u00edguez Antol\u00edn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe","family":"Cou\u00f1ago","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelia","family":"Sanmamed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Dom\u00ednguez Esteban","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"L\u00f3pez Valc\u00e1rcel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ray","family":"Manneh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1ngel","family":"Borque-Fernando","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuria","family":"Sala Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Maroto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"B1","volume-title":"Cancer today data: prostate cancer","year":"2022"},{"key":"B2","article-title":"Cancer tomorrow data: prostate cancer","year":"2022","journal-title":"Int Agency Res Cancer"},{"key":"B3","article-title":"Global cancer observatory fact sheet","year":"2022","journal-title":"Prostate: Int Agency Res Cancer"},{"key":"B4","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.acuroe.2022.02.009","article-title":"Incidence, prevalence, and treatment patterns in metastatic hormone-sensitive prostate cancer in Spain: ECHOS study","volume":"46","author":"de Velasco Oria de Rueda","year":"2022","journal-title":"Actas Urol\u00f3gicas Espa\u00f1olas (English Edition)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e390166","DOI":"10.1200\/EDBK_390166","article-title":"Metastatic hormone-sensitive prostate cancer: toward an era of adaptive and personalized treatment","volume":"43","author":"Hamid","year":"2023","journal-title":"Am Soc Clin Oncol Educ book. 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