{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T15:06:14Z","timestamp":1783177574211,"version":"3.54.6"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The best choice of first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. We aimed to compare the effectiveness and safety determined in randomized clinical trials of doublet and triplet treatments for mHSPC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Medline, Embase, Cochrane Central and ClinicalTrials.gov were searched from inception through July 01, 2022. Eligible studies were phase III randomized clinical trials evaluating androgen deprivation treatment (ADT) alone, doublet therapies [ADT combined with docetaxel (DOC), novel hormonal agents (NHAs), or radiotherapy (RT)], or triplet therapies (NHA+DOC+ADT) as first-line treatments for mHSPC. Outcomes of interest included overall survival (OS), progression-free survival (PFS) and grades 3-5 adverse events (AEs). Subgroup analyses were performed based on tumor burden. The effects of competing treatments were assessed by Bayesian network meta-analysis using R software.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ten trials with 12,298 patients comparing nine treatments were included. Darolutamide (DARO) +DOC+ADT ranked best in terms of OS benefits (OR 0\u00b752 [95% CI 0\u00b739\u20130\u00b770]), but its advantages were all statistically insignificant compared with other therapy options except for DOC+ADT (OR 0\u00b768 [95% CI 0\u00b753\u20130\u00b788]) and RT+ADT (OR 0\u00b757 [95% CI 0\u00b740\u20130\u00b780]). In terms of PFS, enzalutamide(ENZA)+DOC+ADT (OR 0\u00b732 [95% CI 0\u00b724\u20130\u00b744]) and abiraterone and prednisone (AAP) +DOC+ADT (OR 0\u00b733 [95% CI 0\u00b725\u20130\u00b745]) ranked best. For patients with high volume disease (HVD), low volume disease (LVD), and visceral metastases, the optimal therapies were AAP+DOC+ADT (OR 0\u00b752 [95% CI 0\u00b733\u20130\u00b783]), apalutamide+ADT (OR 0\u00b752 [95% CI 0\u00b726\u20131\u00b705]) and DARO+DOC+ADT (OR 0\u00b742 [95% CI 0\u00b713\u20131\u00b734]), respectively. For safety, AAP+DOC+ADT (OR 3\u00b756 [95% CI 1\u00b751\u20138\u00b743]) ranked worst with the highest risk of grade 3\u22125 AEs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Triple therapies may further improve OS and PFS but may be associated with a decrease in safety. Triplet therapies could be suggested for HVD patients, while doublet combinations should still be preferred for LVD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic Review Registration<\/jats:title><jats:p><jats:uri>https:\/\/www.crd.york.ac.uk\/PROSPEROFILES\/303117_STRATEGY_20220202.pdf<\/jats:uri>, identifier CRD4202303117.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2023.1104242","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T05:32:50Z","timestamp":1678167170000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Comparison of doublet and triplet therapies for metastatic hormone-sensitive prostate cancer: A systematic review and network 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