{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:17:11Z","timestamp":1788283031160,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000},"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":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Genomic defects in DNA\u2010damage repair (DDR) mechanisms have been proposed to affect the radiosensitivity of prostate cancers. In this study, we intended to evaluate the prevalence of genetic alterations in a cohort of metastatic castration\u2010resistant prostate cancer (mCRPC) patients undergoing radioligand therapy (RLT) with prostate\u2010specific membrane antigen (PSMA)\u2010inhibitors as well as the impact of such mutations on treatment outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data of consecutive mCRPC patients from 2017 to 2021 who were treated with PSMA\u2010RLT and underwent next\u2010generation sequencing (NGS) were collected and analyzed for response and survival outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In 95 patients of mCRPC treated with PSMA\u2010RLT, 15 patients (median age: 66 years, range: 50\u201373 years; [<jats:sup>177<\/jats:sup>Lu]Lu\u2010PSMA\u2010617,<jats:italic>n<\/jats:italic>\u2009=\u200912; [<jats:sup>225<\/jats:sup>Ac]Ac\u2010PSMA\u2010617,<jats:italic>n<\/jats:italic>\u2009=\u20093) underwent NGS. The median progression\u2010free survival (PFS) of this cohort was 3 months (95% confidence interval: 1.6\u20134.4 months). On NGS, 21 genetic alterations were reported in 10\/15 (67%) patients, of which 13 were DDR\u2010associated alterations involving the genes:<jats:italic>ATM<\/jats:italic>(<jats:italic>n<\/jats:italic>\u2009=\u20093),<jats:italic>BRCA2<\/jats:italic>(<jats:italic>n<\/jats:italic>\u2009=\u20093),<jats:italic>TP53<\/jats:italic>(<jats:italic>n<\/jats:italic>\u2009=\u20092),<jats:italic>PTEN<\/jats:italic>(<jats:italic>n<\/jats:italic>\u2009=\u20092),<jats:italic>FANCD2<\/jats:italic>(<jats:italic>n<\/jats:italic>\u2009=\u20091),<jats:italic>FANCM<\/jats:italic>(<jats:italic>n<\/jats:italic>\u2009=\u20091), and<jats:italic>NBN<\/jats:italic>(<jats:italic>n<\/jats:italic>\u2009=\u20091). Overall, 5\/15 (33%) patients harbored six pathogenic variants (<jats:italic>BRCA2<\/jats:italic>,<jats:italic>n<\/jats:italic>\u2009=\u20092;<jats:italic>ATM<\/jats:italic>,<jats:italic>n<\/jats:italic>\u2009=\u20091;<jats:italic>TP53<\/jats:italic>,<jats:italic>n<\/jats:italic>\u2009=\u20091;<jats:italic>PTEN<\/jats:italic>,<jats:italic>n<\/jats:italic>\u2009=\u20092). No significant difference was noted for the biochemical response, radiological response, PFS, and overall survival between the patients with and without genetic alterations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patients of mCRPC undergoing PSMA\u2010RLT were frequently seen to harbor DDR\u2010associated aberrations, albeit with no significant impact on treatment outcomes. Large prospective trials comparing PSMA\u2010RLT\u2010related outcomes in DDR\u2010deficient and \u2010proficient patients are required to bring out the differences, if any, in a more observable manner.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24450","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T08:08:20Z","timestamp":1666166900000},"page":"169-178","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Genomic characterization of metastatic castration\u2010resistant prostate cancer patients undergoing PSMA radioligand therapy: A single\u2010center experience"],"prefix":"10.1002","volume":"83","author":[{"given":"Swayamjeet","family":"Satapathy","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine Post Graduate Institute of Medical Education and Research Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2159-8227","authenticated-orcid":false,"given":"Chandan K.","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology and Medical Oncology Post Graduate Institute of Medical Education and Research Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyush","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Post Graduate Institute of Medical Education and Research Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7228-0361","authenticated-orcid":false,"given":"Ashwani","family":"Sood","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Post Graduate Institute of Medical Education and Research Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwin S.","family":"Parihar","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Post Graduate Institute of Medical Education and Research Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrawan K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Urology Post Graduate Institute of Medical Education and Research Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5318-6644","authenticated-orcid":false,"given":"Bhagwant R.","family":"Mittal","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Post Graduate Institute of Medical Education and Research Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107322"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00237-3"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-021-05618-3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41391-021-00349-w"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23912"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-020-04723-z"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.35759"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/RLU.0000000000003307"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2016.08.037"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2020-0697"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2009.06.016"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/238757"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2018.03.007"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.119.234559"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/35071124"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijnm.IJNM_130_20"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.2702"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01114-x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.629266"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2016.09.001"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2018.09.040"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2020.05.001"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/RLU.0000000000002141"},{"key":"e_1_2_8_26_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.18.00237","article-title":"Exceptional response to 177Lutetium prostate\u2010specific membrane antigen in prostate cancer harboring DNA repair defects","volume":"3","author":"Crumbaker M","year":"2019","journal-title":"JCO Precis Oncol"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/RLU.0000000000003541"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41391-021-00424-2"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20805"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2021.03.004"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9040430"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-15-0945"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.24450","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pros.24450","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.24450","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T03:36:40Z","timestamp":1701229000000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.24450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,19]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1002\/pros.24450"],"URL":"https:\/\/doi.org\/10.1002\/pros.24450","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,19]]},"assertion":[{"value":"2022-08-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}