Zapatero, AlmudenaAlonso Gordoa, TeresaRodríguez Antolín, AlfredoCouñago Lorenzo, FelipeSanmamed Salgado, NoeliaDomínguez Esteban, MarioLópez Valcárcel, NuriaMaroto, Pablo2025-09-262025-09-262025Zapatero, A., Alonso-Gordoa, T., Rodríguez Antolín, A., Couñago, F., Sanmamed, N., Domínguez Esteban, M., López Valcárcel, M., Manneh, R., Borque-Fernando, Á., Sala González, N., & Maroto, P. (2025). Triplet systemic therapy for hormone-sensitive prostate cancer: A critical review with a multidisciplinary approach. Oncology Reviews, 19, 1599292. https://doi.org/10.3389/or.2025.15992921970-55651970-5557https://hdl.handle.net/11268/16221This 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.engAttribution 4.0 Internationalhttps://creativecommons.org/licenses/by/4.0/Neoplasias de la PróstataAntineoplásicos HormonalesAndrógenosjournal article10.3389/or.2025.1599292open accessCáncerHombreTerapiaGoal 3: Ensure healthy lives and promote well-being for all at all ages