{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:08:06Z","timestamp":1778641686648,"version":"3.51.4"},"reference-count":200,"publisher":"Innovative Healthcare Institute","issue":"2","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Prostate cancer is the most common non-cutaneous malignancy affecting men in the United States, with the incidence of metastatic disease rising. Despite modern androgen deprivation therapy (ADT), nearly all cases of metastatic prostate cancer develop castration resistance. Informed by successes in the treatment of metastatic castration-resistant prostate cancer (mCRPC), novel treatment modalities have emerged as part of the armamentarium for metastatic hormone-sensitive prostate cancer (mHSPC). In this review, we detail treatments such as cytotoxic chemotherapy, androgen receptor pathway inhibitors (ARPIs), radiotherapy, radiopharmaceutical therapy, immunotherapy, and poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of mHSPC, synthesizing current evidence and guiding clinical decision-making. With technological advances and insight from molecular studies, we discuss emerging biomarkers as indicators to guide prognostication and therapeutic decisions. As a result of these developments, the treatment landscape for mHSPC is evolving toward a precision oncology paradigm incorporating combined systemic therapies.<\/jats:p>","DOI":"10.36401\/jipo-25-22","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T02:09:54Z","timestamp":1778638194000},"page":"62-78","source":"Crossref","is-referenced-by-count":0,"title":["Emerging Therapeutic Strategies in Metastatic Hormone-Sensitive Prostate Cancer"],"prefix":"10.36401","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1439-5918","authenticated-orcid":true,"given":"Elias A.","family":"Castro","sequence":"first","affiliation":[{"name":"Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yash C.","family":"Jani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet A.","family":"Bilen","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"22027","reference":[{"key":"i2590-017X-9-2-62-b01","series-title":"Prostate Cancer Prostatic Dis","first-page":"552","article-title":"Trends in prostate cancer mortality in the United States of America, by state and race, from 1999 to 2019: estimates from the centers for disease control WONDER database","volume":"26","author":"Jani","year":"2023","unstructured":"Jani C,\nMouchati C,\nAbdallah N, et al. Trends in prostate cancer mortality in the United States of America, by state and race, from 1999 to 2019: estimates from the centers for disease control WONDER database. Prostate Cancer Prostatic Dis. 2023;26:552\u2013562."},{"key":"i2590-017X-9-2-62-b02","series-title":"CA Cancer J Clin","first-page":"17","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","unstructured":"Siegel RL,\nMiller KD,\nWagle NS,\nJemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17\u201348."},{"key":"i2590-017X-9-2-62-b03","series-title":"Prostate Cancer Prostatic Dis","first-page":"395","article-title":"Increasing incidence of metastatic prostate cancer in the United States (2004-2013)","volume":"19","author":"Weiner","year":"2016","unstructured":"Weiner AB,\nMatulewicz RS,\nEggener SE,\nSchaeffer EM. Increasing incidence of metastatic prostate cancer in the United States (2004-2013). Prostate Cancer Prostatic Dis. 2016;19:395\u2013397."},{"key":"i2590-017X-9-2-62-b04","series-title":"Nat Genet","first-page":"736","article-title":"Spatial genomic heterogeneity within localized, multifocal prostate cancer","volume":"47","author":"Boutros","year":"2015","unstructured":"Boutros PC,\nFraser M,\nHarding NJ, et al. Spatial genomic heterogeneity within localized, multifocal prostate cancer. Nat Genet. 2015;47:736\u2013745."},{"key":"i2590-017X-9-2-62-b05","series-title":"Cancer","first-page":"3787","article-title":"Racial disparities in Black men with prostate cancer: a literature review","volume":"128","author":"Lillard","year":"2022","unstructured":"Lillard JW Jr,\nMoses KA,\nMahal BA,\nGeorge DJ. Racial disparities in Black men with prostate cancer: a literature review. 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Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED Trial. J Clin Oncol. 2018;36:1080\u20131087."},{"key":"i2590-017X-9-2-62-b14","series-title":"Eur Urol","first-page":"256","article-title":"Androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in metastatic non castrate prostate cancer: impact of metastatic burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 Trial","volume":"70","author":"Gravis","year":"2016","unstructured":"Gravis G,\nBoher JM,\nJoly F, et al. Androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in metastatic non castrate prostate cancer: impact of metastatic burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 Trial. Eur Urol. 2016;70:256\u2013262."},{"key":"i2590-017X-9-2-62-b15","series-title":"Lancet","first-page":"1163","article-title":"Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial","volume":"387","author":"James","year":"2016","unstructured":"James ND,\nSydes MR,\nClarke NW, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387:1163\u20131177."},{"key":"i2590-017X-9-2-62-b16","series-title":"Lancet Oncol","first-page":"783","article-title":"Which patients with metastatic hormone-sensitive prostate cancer benefit from docetaxel: a systematic review and meta-analysis of individual participant data from randomised trials","volume":"24","author":"Vale","year":"2023","unstructured":"Vale CL,\nFisher DJ,\nGodolphin PJ, et al. Which patients with metastatic hormone-sensitive prostate cancer benefit from docetaxel: a systematic review and meta-analysis of individual participant data from randomised trials. Lancet Oncol. 2023;24:783\u2013797."},{"key":"i2590-017X-9-2-62-b17","series-title":"Cancers (Basel)","first-page":"1534","article-title":"Androgen receptor-dependent mechanisms mediating drug resistance in prostate cancer","volume":"13","author":"Ehsani","year":"2021","unstructured":"Ehsani M,\nDavid FO,\nBaniahmad A. 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Improved survival with enzalutamide in patients with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2022;40:1616\u20131622."},{"key":"i2590-017X-9-2-62-b28","series-title":"Lancet Oncol","first-page":"323","article-title":"Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial","volume":"24","author":"Sweeney","year":"2023","unstructured":"Sweeney CJ,\nMartin AJ,\nStockler MR, et al. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. 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Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: long-term results from the STAMPEDE randomised controlled trial. PLoS Med. 2022;19:e1003998."},{"key":"i2590-017X-9-2-62-b40","series-title":"Eur Urol","first-page":"410","article-title":"Effect on survival of androgen deprivation therapy alone compared to androgen deprivation therapy combined with concurrent radiation therapy to the prostate in patients with primary bone metastatic prostate cancer in a prospective randomised clinical trial: data from the HORRAD Trial","volume":"75","author":"Boev\u00e9","year":"2019","unstructured":"Boev\u00e9 LMS,\nHulshof MCCM,\nVis AN, et al. Effect on survival of androgen deprivation therapy alone compared to androgen deprivation therapy combined with concurrent radiation therapy to the prostate in patients with primary bone metastatic prostate cancer in a prospective randomised clinical trial: data from the HORRAD Trial. 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Efficacy and safety of prostate radiotherapy in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2\u2009\u00d7\u20092 factorial design. Lancet. 2024;404:2065\u20132076."},{"key":"i2590-017X-9-2-62-b43","series-title":"Eur Urol","first-page":"10","article-title":"Prostate radiotherapy in low-volume metastatic hormone-sensitive prostate cancer: a network meta-analysis","volume":"86","author":"Roy","year":"2024","unstructured":"Roy S,\nFervaha G,\nSpratt DE, et al. Prostate radiotherapy in low-volume metastatic hormone-sensitive prostate cancer: a network meta-analysis. Eur Urol. 2024;86:10\u201317."},{"key":"i2590-017X-9-2-62-b44","series-title":"Radiopharma Ther","first-page":"13","article-title":"A brief history of radiopharmaceutical therapy","author":"Cederquist","year":"2023","unstructured":"Cederquist GY,\nEscorcia FE. A brief history of radiopharmaceutical therapy. 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