{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:55:10Z","timestamp":1792122910928,"version":"4.4.0"},"reference-count":210,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prostate cancer (PCa) remains one of the most prevalent malignancies among men worldwide and continues to pose significant therapeutic challenges, especially in its metastatic and castration-resistant forms. Over the past two decades, the treatment paradigm has evolved from monotherapy with androgen deprivation therapy (ADT) to a multifaceted approach integrating chemotherapy, androgen receptor axis-targeted therapies (ARATs), radiopharmaceuticals, and precision medicine. This review explores the molecular underpinnings of PCa, including genetic and epigenetic alterations such as BRCA1\/2, TP53, and PTEN mutations, and their role in disease progression and treatment resistance. We detail the evidence supporting the integration of systemic agents like abiraterone, enzalutamide, and darolutamide into both hormone-sensitive and castration-resistant settings. Furthermore, we highlight the expanding role of radioligand therapies, including radium-223 and Lutetium-177-labeled PSMA-617 (Lu-PSMA-617), as well as the growing impact of PARP inhibitors in genomically selected patients. The emergence of theranostic strategies and next-generation sequencing has paved the way for personalized treatment algorithms, moving toward a truly precision oncology model in PCa. This comprehensive review synthesizes current therapeutic strategies, clinical trial evidence, and future directions aimed at optimizing outcomes and quality of life for patients with advanced prostate cancer.<\/jats:p>","DOI":"10.3390\/ijms262311665","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T08:49:22Z","timestamp":1764665362000},"page":"11665","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Therapeutic Advances in Metastatic Prostate Cancer: A Journey from Standard of Care to New Emerging Treatment"],"prefix":"10.3390","volume":"26","author":[{"given":"Rossella","family":"Cicchetti","sequence":"first","affiliation":[{"name":"Department of Medical Oral and Biotechnological Science, Universit\u00e0 degli Studi \u201cG. d\u2019Annunzio\u201d of Chieti, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Basconi","sequence":"additional","affiliation":[{"name":"Department of Medical Oral and Biotechnological Science, Universit\u00e0 degli Studi \u201cG. d\u2019Annunzio\u201d of Chieti, 66100 Chieti, Italy"}],"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 Medical Oral and Biotechnological Science, Universit\u00e0 degli Studi \u201cG. d\u2019Annunzio\u201d of Chieti, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9372-5847","authenticated-orcid":false,"given":"Angelo","family":"Orsini","sequence":"additional","affiliation":[{"name":"Department of Medical Oral and Biotechnological Science, Universit\u00e0 degli Studi \u201cG. d\u2019Annunzio\u201d of Chieti, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Mascitti","sequence":"additional","affiliation":[{"name":"Department of Medical Oral and Biotechnological Science, Universit\u00e0 degli Studi \u201cG. d\u2019Annunzio\u201d of Chieti, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9312-2266","authenticated-orcid":false,"given":"Alessio","family":"Digiacomo","sequence":"additional","affiliation":[{"name":"Department of Medical Oral and Biotechnological Science, Universit\u00e0 degli Studi \u201cG. d\u2019Annunzio\u201d of Chieti, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Salzano","sequence":"additional","affiliation":[{"name":"Department of Medical Oral and Biotechnological Science, Universit\u00e0 degli Studi \u201cG. d\u2019Annunzio\u201d of Chieti, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7057-7815","authenticated-orcid":false,"given":"Octavian Sabin","family":"T\u0103taru","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Surgery and Anesthesiology and Intensive Care, Faculty of Medicine, University Dimitrie Cantemir, 540545 Targu Mures, Romania"},{"name":"Department of Urology, ASSR Santi Paolo e Carlo, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Ferro","sequence":"additional","affiliation":[{"name":"Department of Urology, ASSR Santi Paolo e Carlo, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9934-4011","authenticated-orcid":false,"given":"Carlo","family":"Giulioni","sequence":"additional","affiliation":[{"name":"Casa di Cura Villa Igea, 60127 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Cafarelli","sequence":"additional","affiliation":[{"name":"Casa di Cura Villa Igea, 60127 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Schips","sequence":"additional","affiliation":[{"name":"Department of Medical Oral and Biotechnological Science, Universit\u00e0 degli Studi \u201cG. d\u2019Annunzio\u201d of Chieti, 66100 Chieti, Italy"}],"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 Science, Universit\u00e0 degli Studi \u201cG. d\u2019Annunzio\u201d of Chieti, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"ref_1","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. 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