{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T19:29:46Z","timestamp":1784575786164,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Targeted radionuclide therapy with Actinium\u2010225\u2010labeled prostate\u2010specific membrane antigen agents (225Ac\u2010PSMA) is currently being studied in clinical trials for patients with metastatic castration\u2010resistant prostate cancer (mCRPC). Compared to \u03b2\u2010emitting therapeutic radionuclides, alpha\u2010emitters (e.g., 225Ac) have a significantly higher linear energy transfer and significantly shorter range. As a result, alpha emitters could be expected to improve efficacy and reduce bystander toxicity. This systematic literature review was conducted to evaluate the impact of sequencing of 177Lu\u2010PSMA and 225Ac\u2010PSMA targeted radionuclide therapy (TRT) in mCRPC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The present systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta\u2010analyses (PRISMA) guidelines. The searches were made using relevant keywords in the PubMed, Scopus, and Web of Science databases, and articles up to August 22, 2022, were included. Publications were excluded if they were duplicate publications, wrong study or publication format, or discussing a topic out of scope. Data on efficacy, toxicity, and health\u2010related quality of life were extracted from the individual articles. The <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> index was used to measure the extent of heterogeneity amongst studies. In the studies that reported subgroup outcomes according to the prior status on 177Lu\u2010PSMA TRT, pooled estimates of the main outcomes were generated through descriptive analysis. Quality assessment was performed using the Newark\u2212Ottawa\u2010scale.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study included 12 articles; 1 series was performed prospectively. In total, data of 329 patients were analyzed. About 40.1% (<jats:italic>n<\/jats:italic>\u2009=\u2009132) of the included men were pretreated with 177Lu\u2010PSMA TRT. Seven studies, including data of 212 individuals, were eligible for quantitative analysis based on reporting outcomes of the subgroups according to their prior status on 177Lu\u2010PSMA TRT. &gt;25% PSA decline after 225Ac\u2010PSMA TRT was lower in individuals who received prior 177Lu\u2010PSMA TRT (pooled median 42.7%) compared to those who did not (pooled median 15.4%). The pooled medians of the reported median progression\u2010free survival and overall survival for pretreated versus not pretreated individuals was 4.3 versus 14.3 months and 11.1 versus 9.2 months, respectively. However, the outcomes for each individual study were reported inconsistently (<jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u200999.9%). None of the included studies stratified the report of adverse events or changes in health\u2010related quality of life for the subgroups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>225Ac\u2010PSMA TRT is an experimental treatment for men with mCRPC. There is limited data available from high\u2010quality trials but so far PSMA\u2010targeted TRT has demonstrated a low morbidity profile. Our review revealed that there is a possible decrease in efficacy of targeted alpha\u2010particle therapy if individuals previously were exposed to 177Lu\u2010PSMA TRT. However, the level of evidence is low. The underlying mechanism by which 177Lu\u2010PSMA TRT might trigger possible radioresistance as well as randomized controlled trials are required to establish the therapeutic efficacy and safety of 225\u2010Ac\u2010PSMA TRT in men refractory to 177Lu\u2010PSMA TRT.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24531","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T07:09:55Z","timestamp":1679641795000},"page":"901-911","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Response to RL\u2010225Ac in prostate cancer: Effect of prior treatment with RL\u2010177Lu: A systematic review of the literature"],"prefix":"10.1002","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8644-2445","authenticated-orcid":false,"given":"Judith","family":"Stangl\u2010Kremser","sequence":"first","affiliation":[{"name":"Department of Urology Weill Cornell Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Ricaurte\u2010Fajardo","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Molecular Imaging and Therapeutics Weill Cornell Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3934-2107","authenticated-orcid":false,"given":"Kritika","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Molecular Imaging and Therapeutics Weill Cornell Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph R.","family":"Osborne","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Molecular Imaging and Therapeutics Weill Cornell Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Medicine Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott T.","family":"Tagawa","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Medicine Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil H.","family":"Bander","sequence":"additional","affiliation":[{"name":"Department of Urology Weill Cornell Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22594-1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107322"},{"key":"e_1_2_8_4_1","unstructured":"Research C for DE and. FDA approves Pluvicto for metastatic castration\u2010resistant prostate cancer.FDA. Published online March 23 2022. Accessed September 19 2022https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.115.158550"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.115.171397"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2021.03.004"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.119.234559"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24234314"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.116.186338"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.108.058651"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064730"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3569"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.116.178673"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt.14.16"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23180"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw065"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000097"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2016142043"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.2702"},{"key":"e_1_2_8_21_1","unstructured":"Common Terminology Criteria for Adverse Events (CTCAE). Protocol development. CTEP. Accessed September 19 2022https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/ctc.htm"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13643-021-01824-0"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-21416-0"},{"key":"e_1_2_8_24_1","doi-asserted-by":"crossref","unstructured":"Ottawa Hospital Research Institute. Accessed January 10 2023.https:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp","DOI":"10.5152\/eurjrheum.2022.21081"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz248.029"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.119.229229"},{"issue":"5","key":"e_1_2_8_28_1","first-page":"669","article-title":"First clinical results for PSMA\u2010targeted \u03b1\u2010therapy using (225)Ac\u2010PSMA\u2010I&T in advanced\u2010mCRPC patients","volume":"62","author":"Zacherl MJ","year":"2021","journal-title":"J Nucl Med Off Publ Soc Nucl Med"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2020.11.013"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2020.12.002"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/RLU.0000000000003925"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.16_suppl.e17025"},{"issue":"4","key":"e_1_2_8_33_1","first-page":"299","article-title":"Health\u2010related quality\u2010of\u2010life outcomes with Actinium\u2010225\u2010prostate\u2010specific membrane Antigen\u2010617 therapy in patients with heavily pretreated metastatic castration\u2010resistant prostate cancer","volume":"35","author":"Satapathy S","year":"2020","journal-title":"Indian J Nucl Med IJNM Off J Soc Nucl Med India"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12149-021-01617-4"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10050946"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-022-05778-w"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.48107"},{"issue":"5","key":"e_1_2_8_38_1","first-page":"669","article-title":"First clinical results for PSMA targeted alpha therapy using 225Ac\u2010PSMA\u2010I&T in advanced mCRPC patients","volume":"62","author":"Zacherl MJ","year":"2021","journal-title":"J Nucl Med Off Publ Soc Nucl Med"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.4044"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz270"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-18-0837"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.121.262017"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12081926"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.3413\/nukmed-0262"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.117.203539"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2404"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2018.03.007"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.24531","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.24531","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T05:02:45Z","timestamp":1692507765000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.24531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,13]]},"references-count":46,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1002\/pros.24531"],"URL":"https:\/\/doi.org\/10.1002\/pros.24531","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,13]]},"assertion":[{"value":"2022-11-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}