{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T15:34:58Z","timestamp":1787326498519,"version":"build-2736575974"},"reference-count":74,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: High-risk prostate cancer is a biologically heterogeneous group of tumors carrying a substantial risk of progression to lethal, castration-resistant disease. Although androgen deprivation therapy (ADT) remains the therapeutic backbone, nearly all advanced disease eventually progresses to castration-resistant prostate cancer (CRPC) through Darwinian clonal evolution under sustained therapeutic pressure. This narrative review reframes high-risk prostate cancer management as an effort to reprogram the evolutionary trajectory and delay castration resistance, addressing current risk stratification, androgen receptor (AR)-dependent and AR-independent mechanisms of resistance, and multidisciplinary strategies that modify selective pressure. Methods: A narrative review of the literature was conducted, including peer-reviewed studies, pivotal phase III trial reports, and current clinical practice guidelines indexed in PubMed, Scopus, and Web of Science up to 2026. Sources on high-risk and castration-resistant prostate cancer, the biology of treatment resistance, and multidisciplinary treatment intensification were selected and synthesized. Results: Treatment intensification has been extended to high-risk biochemical recurrence (EMBARK), directed by biomarkers in PTEN-deficient disease (CAPItello-281), and moved earlier through prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PSMAfore, PSMAddition). In localized disease, effective AR-pathway intensification with abiraterone (STAMPEDE) contrasts with the failure of chemotherapy (PEACE-2) and enzalutamide (ENZARAD). Emerging therapies targeting lineage plasticity exploit its dynamic and potentially reversible biology, raising the prospect of reversing established resistance rather than merely delaying it. CAPItello-281 and PSMAddition have immature overall survival data and are not yet standard of care. Conclusions: Coordinated multidisciplinary care, matched to the disease stage and molecular context, offers a realistic path to delay castration resistance and improve survival.<\/jats:p>","DOI":"10.3390\/jcm15166488","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:20:36Z","timestamp":1787322036000},"page":"6488","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reprogramming the Evolution of High-Risk Prostate Cancer: Multidisciplinary Strategies to Delay Castration Resistance"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6173-8871","authenticated-orcid":false,"given":"Younghun","family":"Sim","sequence":"first","affiliation":[{"name":"Department of Urology, Hanyang University Seoul Hospital, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Won","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Urology, Hanyang University Seoul Hospital, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Seob","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Urology, Hanyang University Seoul Hospital, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Urology, Kangwon National University School of Medicine, Chuncheon 24289, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3136-7935","authenticated-orcid":false,"given":"Sung Goo","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Urology, Hanyang University Seoul Hospital, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6080-7493","authenticated-orcid":false,"given":"Jung Ki","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Urology, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.prnil.2018.11.001","article-title":"The incidence, mortality, and risk factors of prostate cancer in Asian men","volume":"7","author":"Chung","year":"2019","journal-title":"Prostate Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.prnil.2015.06.003","article-title":"Epidemiology of prostate cancer in South Korea","volume":"3","author":"Han","year":"2015","journal-title":"Prostate Int."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Burgess, L., Roy, S., Morgan, S., and Malone, S. (2021). A Review on the Current Treatment Paradigm in High-Risk Prostate Cancer. Cancers, 13.","DOI":"10.3390\/cancers13174257"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrc4016","article-title":"Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer","volume":"15","author":"Watson","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1056\/NEJMoa1503747","article-title":"Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer","volume":"373","author":"Sweeney","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/S0140-6736(15)01037-5","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","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.eururo.2020.01.033","article-title":"Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer: An International Multidisciplinary Systematic Review","volume":"77","author":"Moris","year":"2020","journal-title":"Eur. Urol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Le, T.K., Duong, Q.H., Baylot, V., Fargette, C., Baboudjian, M., Colleaux, L., Ta\u00efeb, D., and Rocchi, P. (2023). Castration-Resistant Prostate Cancer: From Uncovered Resistance Mechanisms to Current Treatments. Cancers, 15.","DOI":"10.3390\/cancers15205047"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"469","DOI":"10.6004\/jnccn.2025.0052","article-title":"Prostate Cancer, Version 3.2026, NCCN Clinical Practice Guidelines In Oncology","volume":"23","author":"Spratt","year":"2025","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_10","unstructured":"Cornford, P., Tilki, D., Van Den Bergh, R.C.N., Eberli, D., Fonteyne, V., Gandaglia, G., Gillessen, S., Henry, A.M., van Leenders, G.J.L.H., and Oldenburg, J. (2026). EAU\u2013EANM\u2013ESTRO\u2013ESUR\u2013ISUP\u2013SIOG Guidelines on Prostate Cancer, European Association of Urology."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.clgc.2015.05.007","article-title":"Association Between Older Age and Increasing Gleason Score","volume":"13","author":"Muralidhar","year":"2015","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1158\/1055-9965.EPI-21-0697","article-title":"Contributions of Social Factors to Disparities in Prostate Cancer Risk Profiles among Black Men and Non-Hispanic White Men with Prostate Cancer in California","volume":"31","author":"Press","year":"2022","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/S0140-6736(20)30314-7","article-title":"Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): A prospective, randomised, multicentre study","volume":"395","author":"Hofman","year":"2020","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.cell.2015.10.025","article-title":"The Molecular Taxonomy of Primary Prostate Cancer","volume":"163","author":"Abeshouse","year":"2015","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.cell.2015.05.001","article-title":"Integrative Clinical Genomics of Advanced Prostate Cancer","volume":"161","author":"Robinson","year":"2015","journal-title":"Cell"},{"key":"ref_16","first-page":"9","article-title":"Overcoming drug resistance in castrate-resistant prostate cancer: Current mechanisms and emerging therapeutic approaches","volume":"8","author":"Khorasanchi","year":"2025","journal-title":"Cancer Drug Resist."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.ccell.2017.09.003","article-title":"Androgen Receptor Pathway-Independent Prostate Cancer Is Sustained through FGF Signaling","volume":"32","author":"Bluemn","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1056\/NEJMoa1315815","article-title":"AR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer","volume":"371","author":"Antonarakis","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1200\/JCO.2017.77.6880","article-title":"Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study","volume":"36","author":"Aggarwal","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3522","DOI":"10.1158\/0008-5472.CAN-24-1388","article-title":"Neuroendocrine Differentiation in Prostate Cancer Requires ASCL1","volume":"84","author":"Rodarte","year":"2024","journal-title":"Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e185952","DOI":"10.1172\/jci.insight.185952","article-title":"ASCL1 regulates and cooperates with FOXA2 to drive terminal neuroendocrine phenotype in prostate cancer","volume":"9","author":"Nouruzi","year":"2024","journal-title":"JCI Insight"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1158\/1078-0432.CCR-18-1912","article-title":"A Phase II Trial of the Aurora Kinase A Inhibitor Alisertib for Patients with Castration-resistant and Neuroendocrine Prostate Cancer: Efficacy and Biomarkers","volume":"25","author":"Beltran","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6779","DOI":"10.1038\/s41467-024-51156-5","article-title":"Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes","volume":"15","author":"Venkadakrishnan","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/s41698-025-01031-3","article-title":"Plasma epigenomic profiling reveals treatment-emergent squamous transformation in prostate cancer","volume":"9","author":"Semaan","year":"2025","journal-title":"npj Precis. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"78","DOI":"10.62347\/ZQCI9925","article-title":"Post-therapeutic squamous cell transformation of a metastatic prostate adenocarcinoma with comparison of molecular profiles: A case report and review of the literature","volume":"17","author":"Li","year":"2024","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1056\/NEJMoa1603144","article-title":"Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer","volume":"375","author":"Pritchard","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1056\/NEJMoa1911440","article-title":"Olaparib for Metastatic Castration-Resistant Prostate Cancer","volume":"382","author":"Mateo","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"362ps17","DOI":"10.1126\/scitranslmed.aaf9246","article-title":"Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action","volume":"8","author":"Pommier","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1001\/jamaoncol.2018.5801","article-title":"Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade","volume":"5","author":"Abida","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1093\/annonc\/mdy495","article-title":"Development of tumor mutation burden as an immunotherapy biomarker: Utility for the oncology clinic","volume":"30","author":"Chan","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1126\/science.1227604","article-title":"EZH2 Oncogenic Activity in Castration-Resistant Prostate Cancer Cells Is Polycomb-Independent","volume":"338","author":"Xu","year":"2012","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"S967","DOI":"10.1016\/j.annonc.2024.08.1684","article-title":"1603P Updated safety and efficacy of tazemetostat (TAZ) plus enzalutamide (ENZ) in patients with metastatic castration-resistant prostate cancer (mCRPC)","volume":"35","author":"Abida","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_33","first-page":"LBA138","article-title":"Mevrometostat (PF-06821497), an enhancer of zeste homolog 2 (EZH2) inhibitor, in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC): A randomized dose-expansion study","volume":"43","author":"Schweizer","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1080\/14796694.2026.2667441","article-title":"Phase III randomized studies of mevrometostat and enzalutamide in metastatic prostate cancer (MEVPRO-1 and MEVPRO-2): Trial protocols","volume":"22","author":"Shore","year":"2026","journal-title":"Future Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S0140-6736(21)02437-5","article-title":"Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: A meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol","volume":"399","author":"Attard","year":"2022","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1056\/NEJMoa2303974","article-title":"Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer","volume":"389","author":"Freedland","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1056\/NEJMoa2510310","article-title":"Improved Survival with Enzalutamide in Biochemically Recurrent Prostate Cancer","volume":"394","author":"Shore","year":"2026","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1056\/NEJMoa1704174","article-title":"Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer","volume":"377","author":"Fizazi","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1903307","article-title":"Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer","volume":"381","author":"Chi","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.1200\/JCO.19.00799","article-title":"ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy with Enzalutamide or Placebo in Men with Metastatic Hormone-Sensitive Prostate Cancer","volume":"37","author":"Armstrong","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1056\/NEJMoa1903835","article-title":"Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer","volume":"381","author":"Davis","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4271","DOI":"10.1200\/JCO-24-01798","article-title":"Darolutamide in Combination with Androgen-Deprivation Therapy in Patients with Metastatic Hormone-Sensitive Prostate Cancer from the Phase III ARANOTE Trial","volume":"42","author":"Saad","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1056\/NEJMoa2119115","article-title":"Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer","volume":"386","author":"Smith","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1016\/S0140-6736(22)00367-1","article-title":"Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): A multicentre, open-label, randomised, phase 3 study with a 2 \u00d7 2 factorial design","volume":"399","author":"Fizazi","year":"2022","journal-title":"Lancet"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.annonc.2025.10.004","article-title":"Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study","volume":"37","author":"Fizazi","year":"2026","journal-title":"Ann. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0140-6736(21)00580-8","article-title":"Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): A multicentre, randomised, double-blind, phase 3 trial","volume":"398","author":"Sweeney","year":"2021","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S1627","DOI":"10.1016\/j.annonc.2025.09.101","article-title":"LBA6 Phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition)","volume":"36","author":"Tagawa","year":"2025","journal-title":"Ann. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1056\/NEJMoa1715546","article-title":"Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer","volume":"378","author":"Smith","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1056\/NEJMoa1800536","article-title":"Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer","volume":"378","author":"Hussain","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1056\/NEJMoa1815671","article-title":"Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer","volume":"380","author":"Fizazi","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1056\/NEJMoa1001294","article-title":"Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer","volume":"363","author":"Kantoff","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1056\/NEJMoa1213755","article-title":"Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer","volume":"369","author":"Parker","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1056\/NEJMoa2107322","article-title":"Lutetium-177\u2013PSMA-617 for Metastatic Castration-Resistant Prostate Cancer","volume":"385","author":"Sartor","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/S0140-6736(21)00237-3","article-title":"[177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): A randomised, open-label, phase 2 trial","volume":"397","author":"Hofman","year":"2021","journal-title":"Lancet"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/S0140-6736(24)01653-2","article-title":"177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): A phase 3, randomised, controlled trial","volume":"404","author":"Morris","year":"2024","journal-title":"Lancet"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0140-6736(23)01055-3","article-title":"Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): A randomised, placebo-controlled, phase 3 trial","volume":"402","author":"Agarwal","year":"2023","journal-title":"Lancet"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1056\/NEJMoa1911206","article-title":"Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer","volume":"381","author":"Sternberg","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1016\/S0140-6736(18)32486-3","article-title":"Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): A randomised controlled phase 3 trial","volume":"392","author":"Parker","year":"2018","journal-title":"Lancet"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"LBA307","DOI":"10.1200\/JCO.2026.44.7_suppl.LBA307","article-title":"Androgen deprivation therapy and radiotherapy with or without cabazitaxel in very-high risk localized prostate cancer: First results of the PEACE-2 randomized phase III trial","volume":"44","author":"Fizazi","year":"2026","journal-title":"J. Clin. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"S1628","DOI":"10.1016\/j.annonc.2025.09.102","article-title":"LBA86 Randomised phase III trial of androgen deprivation therapy (ADT) with radiation therapy with or without enzalutamide for high risk, clinically localised prostate cancer: ENZARAD (ANZUP 1303)","volume":"36","author":"Nguyen","year":"2025","journal-title":"Ann. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.radonc.2022.10.028","article-title":"Trends and variation in the use of radiotherapy in non-metastatic prostate cancer: A 12-year nationwide overview from the Netherlands","volume":"177","author":"Evers","year":"2022","journal-title":"Radiother. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"899","DOI":"10.4143\/crt.2015.212","article-title":"Changing Patterns of Primary Treatment in Korean Men with Prostate Cancer Over 10 Years: A Nationwide Population Based Study","volume":"48","author":"Park","year":"2016","journal-title":"Cancer Res. Treat."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.eururo.2019.02.003","article-title":"Prostate Radiotherapy for Metastatic Hormone-sensitive Prostate Cancer: A STOPCAP Systematic Review and Meta-analysis","volume":"76","author":"Burdett","year":"2019","journal-title":"Eur. Urol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.prnil.2022.03.001","article-title":"Genomic analysis and long-term outcomes of a phase 1 clinical trial on cytoreductive radical prostatectomy","volume":"10","author":"Kim","year":"2022","journal-title":"Prostate Int."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1200\/JCO.2017.75.4853","article-title":"Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial","volume":"36","author":"Ost","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1001\/jamaoncol.2020.0147","article-title":"Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial","volume":"6","author":"Phillips","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"95","DOI":"10.12954\/PI.13018","article-title":"The role of radical prostatectomy in high-risk prostate cancer","volume":"1","author":"Chung","year":"2013","journal-title":"Prostate Int."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1080\/21681805.2018.1520295","article-title":"SPCG-15: A prospective randomized study comparing primary radical prostatectomy and primary radiotherapy plus androgen deprivation therapy for locally advanced prostate cancer","volume":"52","author":"Stranne","year":"2018","journal-title":"Scand. J. Urol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.1200\/JCO.20.00315","article-title":"Cancer and Leukemia Group B 90203 (Alliance): Radical Prostatectomy With or Without Neoadjuvant Chemohormonal Therapy in Localized, High-Risk Prostate Cancer","volume":"38","author":"Eastham","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13012-018-0733-x","article-title":"A multidisciplinary team-oriented intervention to increase guideline recommended care for high-risk prostate cancer: A stepped-wedge cluster randomised implementation trial","volume":"13","author":"Brown","year":"2018","journal-title":"Implement. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1111\/bju.16577","article-title":"Real-world use of androgen-deprivation therapy intensification for metastatic hormone-sensitive prostate cancer: A systematic review","volume":"135","author":"Raval","year":"2025","journal-title":"BJU Int."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3854","DOI":"10.1158\/1078-0432.CCR-25-1211","article-title":"Safety and Efficacy of Tarlatamab in Patients with Neuroendocrine Prostate Cancer: Results from the Phase 1b DeLLpro-300 Study","volume":"31","author":"Aggarwal","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.prnil.2023.07.002","article-title":"Prostate-specific antigen kinetics in hypofractionated radiation therapy alone for intermediate- and high-risk localized prostate cancer","volume":"11","author":"Lee","year":"2023","journal-title":"Prostate Int."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.prnil.2015.02.006","article-title":"Predictors of survival in prostate cancer patients with bone metastasis and extremely high prostate-specific antigen levels","volume":"3","author":"Koo","year":"2015","journal-title":"Prostate Int."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/16\/6488\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:32:13Z","timestamp":1787322733000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/16\/6488"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":74,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["jcm15166488"],"URL":"https:\/\/doi.org\/10.3390\/jcm15166488","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]}}}