{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T22:59:04Z","timestamp":1784415544821,"version":"3.55.0"},"reference-count":22,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: The combination of Lutetium-177 (Lu-177) PSMA-617 radioligand therapy (RLT) with androgen receptor pathway inhibitors (ARPIs) has shown promise in metastatic castration-resistant prostate cancer (mCRPC). However, real-world data on the efficacy and safety of this combination are limited. This study aimed to evaluate the impact of combination therapy with Lu-177 PSMA-617 RLT and ARPIs on progression-free survival (PFS) and overall survival (OS) in patients with mCRPC. Methods: In this retrospective study, 104 mCRPC patients receiving Lu-177 PSMA-617 RLT at our institution between December 2017 and January 2024 were divided into the following two groups those receiving Lu-177 PSMA-617 RLT plus ARPI (n = 34) and those receiving Lu-177 PSMA-617 RLT alone (n = 70). Patients received 150 to 200 millicuries Lu-177 PSMA-617 RLT in each cycle. PFS and zOS were assessed using Kaplan\u2013Meier analysis and Cox proportional hazard models. Results: The combination therapy significantly prolonged median PFS compared to Lu-177 PSMA-617 RLT alone (11 vs. 5.6 months; HR, 0.47; 95% CI, 0.28\u20130.79; p &lt; 0.01). A trend towards improved OS was also observed in the combination group (20.3 vs. 15.9 months; HR, 0.58; 95% CI, 0.33\u20131.02; p = 0.06). Age was a significant predictor of OS (21.2 vs. 12.4 months for younger vs. older patients; p &lt; 0.01), while Gleason score and visceral involvement did not significantly impact PFS. The safety profile indicated that adverse effects were generally comparable between the two groups, with no statistically significant differences in the incidence of anemia, neutropenia, thrombocytopenia, nephrotoxicity, or hepatotoxicity. Conclusions: This study provides evidence that combining Lu-177 PSMA-617 RLT with ARPIs may significantly improve PFS in mCRPC patients. The potential OS benefit warrants further investigation in larger prospective trials. Age should be considered when making treatment decisions for mCRPC patients.<\/jats:p>","DOI":"10.3390\/jcm13164585","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T08:07:59Z","timestamp":1722931679000},"page":"4585","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Investigating Combination Therapy: The Role of Lutetium-177 PSMA-617 Radioligand Therapy and Androgen Receptor Pathway Inhibitors in Metastatic Castration-Resistant Prostate Cancer"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5983-3291","authenticated-orcid":false,"given":"O\u011fuzcan","family":"K\u0131n\u0131ko\u011flu","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Health Science University, Kartal Dr. Lu\u0308tfi Kirdar City Hospital, \u0130stanbul 34865, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9921-4089","authenticated-orcid":false,"given":"Bala Ba\u015fak","family":"\u00d6ven","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Yeditepe University Medical Faculty, \u0130stanbul 34718, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serkan","family":"\u00c7elik","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Yeditepe University Medical Faculty, \u0130stanbul 34718, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nalan","family":"Alan Sel\u00e7uk","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Yeditepe University Medical Faculty, \u0130stanbul 34718, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamze","family":"Beyda\u011f\u0131","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Yeditepe University Medical Faculty, \u0130stanbul 34718, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaan","family":"Ak\u00e7ay","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Yeditepe University Medical Faculty, \u0130stanbul 34718, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levent","family":"Kabasakal","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Istanbul University Cerrahpa\u015fa Medical Faculty, \u0130stanbul 34098, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.14740\/wjon1191","article-title":"Epidemiology of Prostate Cancer","volume":"10","author":"Rawla","year":"2019","journal-title":"World J. Oncol."},{"key":"ref_2","first-page":"122","article-title":"Current clinical challenges in prostate cancer","volume":"2","author":"Silberstein","year":"2013","journal-title":"Transl. Androl. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7263","DOI":"10.2147\/OTT.S117176","article-title":"Androgen deprivation therapy as backbone therapy in the management of prostate cancer","volume":"9","author":"Merseburger","year":"2016","journal-title":"Onco Targets Ther."},{"key":"ref_4","first-page":"457","article-title":"A review of the pathophysiological mechanisms underlying castration-resistant prostate cancer","volume":"13","author":"Crowley","year":"2021","journal-title":"Res. Rep. Urol."},{"key":"ref_5","first-page":"365","article-title":"Mechanisms of resistance in castration-resistant prostate cancer (CRPC)","volume":"4","author":"Chandrasekar","year":"2015","journal-title":"Transl. Androl. Urol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1056\/NEJMoa1014618","article-title":"Abiraterone and Increased Survival in Metastatic Prostate Cancer","volume":"364","author":"Logothetis","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1056\/NEJMoa1405095","article-title":"Enzalutamide in Metastatic Prostate Cancer before Chemotherapy","volume":"371","author":"Beer","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_8","first-page":"e37778","article-title":"Treatment of Advanced Metastatic Prostate Cancer Using Molecular-Targeted Therapy: Radioligand Lutetium-177 Prostate-Specific Membrane Antigen","volume":"15","author":"Rathore","year":"2023","journal-title":"Cureus"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17588359211053898","DOI":"10.1177\/17588359211053898","article-title":"PSMA targeting in metastatic castration-resistant prostate cancer: Where are we and where are we going?","volume":"13","author":"Giraudet","year":"2021","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1002\/pros.24219","article-title":"Combined 177Lu-PSMA-617 PRLT and abiraterone acetate versus 177Lu-PSMA-617 PRLT monotherapy in metastatic castration-resistant prostate cancer: An observational study comparing the response and durability","volume":"81","author":"Suman","year":"2021","journal-title":"Prostate"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_13","unstructured":"National Cancer Institute (2017). Common Terminology Criteria for Adverse Events (CTCAE) Common Terminology Criteria for Adverse Events (CTCAE) v5.0., National Cancer Institute."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"E957","DOI":"10.1093\/oncolo\/oyac216","article-title":"177Lu-PSMA Therapy for Metastatic Castration-Resistant Prostate Cancer: A Mini-Review of State-of-the-Art","volume":"27","author":"Alsadi","year":"2022","journal-title":"Oncologist"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/ijc.34749","article-title":"The real-world outcomes of Lutetium-177 PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer: Turkish Oncology Group multicenter study","volume":"154","author":"Almuradova","year":"2024","journal-title":"Int. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3724","DOI":"10.18632\/oncotarget.12554","article-title":"Androgen receptor-dependent and-independent mechanisms driving prostate cancer progression: Opportunities for therapeutic targeting from multiple angles","volume":"8","author":"Hoang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/s41585-020-00400-w","article-title":"Genomic and phenotypic heterogeneity in prostate cancer","volume":"18","author":"Haffner","year":"2021","journal-title":"Nat. Rev. Urol."},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1634\/theoncologist.2020-0100","article-title":"A Retrospective Analysis of the Safety and Activity of Lutetium-177-Prostate-Specific Membrane Antigen Radionuclide Treatment in Older Patients with Metastatic Castration-Resistant Prostate Cancer","volume":"25","author":"Leibowitz","year":"2020","journal-title":"Oncologist"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s11523-021-00801-w","article-title":"Real-World Data Analysis of Efficacy and Survival After Lutetium-177 Labelled PSMA Ligand Therapy in Metastatic Castration-Resistant Prostate Cancer","volume":"16","author":"Meyrick","year":"2021","journal-title":"Target. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S1324","DOI":"10.1016\/j.annonc.2023.10.085","article-title":"LBA13 Phase III trial of [177Lu]Lu-PSMA-617 in taxane-naive patients with metastatic castration-resistant prostate cancer (PSMAfore)","volume":"34","author":"Sartor","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_22","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"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/16\/4585\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:30:36Z","timestamp":1760110236000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/16\/4585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,6]]},"references-count":22,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["jcm13164585"],"URL":"https:\/\/doi.org\/10.3390\/jcm13164585","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,6]]}}}