{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T21:35:39Z","timestamp":1783632939276,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T00:00:00Z","timestamp":1561680000000},"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":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Our study aims to investigate the association between copy number of the androgen receptor (AR) and testosterone levels in metastatic castration\u2010resistant prostate cancer (mCRPC) treated with second\u2010generation antiandrogen therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We retrospectively collected data from mCRPC treated with abiraterone acetate and enzalutamide. Serum testosterone levels were collected at baseline, at 3 months since the start of therapy and at disease progression. A cohort of cases treated with docetaxel was also used to evaluate the impact of testosterone levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients treated with abiraterone with <jats:italic>AR<\/jats:italic> copy number aberrations and basal testosterone levels below 0.09\u2009nmol\/L had worse progression\u2010free survival (PFS) compared to patients with no \n<jats:italic>AR<\/jats:italic> copy number abnormalities (8.5 vs 2.9 months, \n<jats:italic>P<\/jats:italic>\u2009=\u20090.005). No relevant differences were observed in the enzalutamide group with a PFS of 3.9 months (no \n<jats:italic>AR<\/jats:italic> gain) vs 2.7 months (\n<jats:italic>AR<\/jats:italic> gain, \n<jats:italic>P<\/jats:italic>\u2009=\u20090.004) for patients with below 0.09\u2009nmol\/L testosterone levels. Similar results are obtained for univariate analysis for overall survival (OS). The negative prognostic role of \n<jats:italic>AR<\/jats:italic> copy number gain in OS for both treatment groups (25.5 vs 10.6 months, \n<jats:italic>P<\/jats:italic>\u2009=\u20090.0002 for abiraterone and 14.1 vs 8.3 months, \n<jats:italic>P<\/jats:italic>\u2009=\u20090.031 for enzalutamide) was confirmed, and it was recognized the negative prognostic impact of testosteronemia below 0.09 only for patients treated with enzalutamide (8.8 vs 42.8 months, \n<jats:italic>P<\/jats:italic>\u2009=\u20090.016). On multivariate analysis for patients treated with abiraterone, low testosterone levels below 0.09 and plasma \n<jats:italic>AR<\/jats:italic> gain were significantly associated with worse PFS and OS. These data are confirmed in the enzalutamide group for PFS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Testosterone levels and the AR copy number alterations were considered as independent prognostic factors. The results of this study show that serum testosteronemia associated with changes in copy number of <jats:italic>AR<\/jats:italic> gene could represent a noninvasive biomarker useful to identify a subgroup of patients with worse prognosis that can benefit less from second\u2010generation antiandrogen therapies in the mCRPC setting.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.23804","type":"journal-article","created":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T20:39:13Z","timestamp":1561754353000},"page":"1211-1220","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Testosterone levels and androgen receptor copy number variations in castration\u2010resistant prostate cancer treated with abiraterone or enzalutamide"],"prefix":"10.1002","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0347-9179","authenticated-orcid":false,"given":"Cristian","family":"Lolli","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Meldola Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia","family":"De Lisi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Campus Bio\u2010Medico University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6921-714X","authenticated-orcid":false,"given":"Vincenza","family":"Conteduca","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Meldola Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Gurioli","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory Division Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Meldola Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Scarpi","sequence":"additional","affiliation":[{"name":"Biostatistics and Clinical Trials Division Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Meldola Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Schepisi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Meldola Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Ravaglia","sequence":"additional","affiliation":[{"name":"Biostatistics and Clinical Trials Division Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Meldola Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Menna","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Meldola Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Farolfi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Meldola Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Altavilla","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Meldola Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore Luca","family":"Burgio","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Meldola Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Tonini","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Campus Bio\u2010Medico University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Santini","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Campus Bio\u2010Medico University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugo","family":"De Giorgi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Meldola Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,28]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21442"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.06.007"},{"key":"e_1_2_7_1_4_1","first-page":"3550","article-title":"Amplification and overexpression of androgen receptor gene in hormone\u2010refractory prostate cancer","volume":"61","author":"Linja MJ","year":"2001","journal-title":"Cancer Res."},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737140.2015.999044"},{"key":"e_1_2_7_1_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22365"},{"key":"e_1_2_7_1_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199505253322101"},{"key":"e_1_2_7_1_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/35094009"},{"key":"e_1_2_7_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2017.02.1653"},{"key":"e_1_2_7_1_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.45.4595"},{"key":"e_1_2_7_1_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2015.128"},{"key":"e_1_2_7_1_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1315815"},{"key":"e_1_2_7_1_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9341"},{"key":"e_1_2_7_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2018.09.049"},{"key":"e_1_2_7_1_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-33774-4"},{"key":"e_1_2_7_1_16_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S100901"},{"key":"e_1_2_7_1_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx155"},{"key":"e_1_2_7_1_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2014.189"},{"key":"e_1_2_7_1_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-1417"},{"key":"e_1_2_7_1_20_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon.15.158"},{"key":"e_1_2_7_1_21_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-14-0071"},{"key":"e_1_2_7_1_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2014.05.008"},{"key":"e_1_2_7_1_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0460"},{"key":"e_1_2_7_1_24_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2558"},{"key":"e_1_2_7_1_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-015-3042-5"},{"key":"e_1_2_7_1_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-2666"},{"key":"e_1_2_7_1_27_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.70.1961"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpros.23804","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.23804","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pros.23804","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.23804","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T17:06:11Z","timestamp":1694279171000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.23804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,28]]},"references-count":26,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["10.1002\/pros.23804"],"URL":"https:\/\/doi.org\/10.1002\/pros.23804","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,28]]},"assertion":[{"value":"2019-02-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}