{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T19:04:04Z","timestamp":1772823844432,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T00:00:00Z","timestamp":1518393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005026","name":"Stichting Tegen Kanker","doi-asserted-by":"publisher","award":["C\/2014\/227"],"award-info":[{"award-number":["C\/2014\/227"]}],"id":[{"id":"10.13039\/501100005026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The outcome to treatment administered to patients with metastatic castration\u2010resistant prostate cancer (mCRPC) greatly differs between individuals, underlining the need for biomarkers guiding treatment decision making.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the prognostic value of circulating tumor cell (CTC) enumeration and dynamics, in the context of second\u2010line endocrine therapies (ie, abiraterone acetate or enzalutamide), irrespective of prior systemic therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Settings, and Participants<\/jats:title><jats:p>In a prospective, multicentre study blood samples for CTC enumeration were collected from patients with mCRPC at baseline (<jats:italic>n\u2009<\/jats:italic>=\u2009174). In patients who responded for minimally 10\u201012 weeks a follow\u2010up sample was collected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Outcome Measurements and Statistical Analysis<\/jats:title><jats:p>For baseline analysis, patients were stratified in &lt;5 or \u22655 CTCs\/7.5\u2009mL, whereas for the analysis of CTC dynamics at 10\u201012 weeks, in patients with stable, increasing or decreasing CTC counts. Progression\u2010free survival (PFS), overall survival (OS), and PSA changes at 10\u201012 weeks were compared between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients demonstrating increasing CTCs on therapy had a shorter median PFS (4.03 vs 12.98 vs 13.67 months, HR 3.6, 95%CI 1.9\u20106.8; <jats:italic>P\u2009<\/jats:italic>&lt;\u20090.0001) and OS (11.2 months vs not reached, HR 9.5, 95%CI 3.7\u201024; <jats:italic>P\u2009<\/jats:italic>&lt;\u20090.0001), compared to patients with decreasing or stable CTCs. Multivariable Cox regression showed that prior chemotherapy (HR 4.1, 95%CI 1.9\u20108.9; <jats:italic>P\u2009<\/jats:italic>=\u20090.0003), a high baseline CTC count (HR 1.5, 95%CI 1.2\u20101.9; <jats:italic>P\u2009<\/jats:italic>=\u20090.002) and increasing CTCs at follow\u2010up (HR 3.3, 95%CI 1.4\u20107.6; <jats:italic>P\u2009<\/jats:italic>=\u20090.005) were independent predictors of worse PFS. Previous chemotherapy (HR 7, 95%CI 1.9\u201025; <jats:italic>P\u2009<\/jats:italic>=\u20090.003), high baseline CTC counts (HR 2.2, 95%CI 1.4\u20103.7; <jats:italic>P\u2009<\/jats:italic>=\u20090.002) and increasing CTCs during therapy (HR 4.6, 95%CI 1.4\u201015; <jats:italic>P\u2009<\/jats:italic>=\u20090.01) were independently associated with shorter OS. \u226530% and \u226550% PSA responses less frequently occurred in patients with CTC inclines at 10\u201012 weeks on therapy (<jats:italic>\u03c7<\/jats:italic><jats:sup>2<\/jats:sup> test: <jats:italic>P\u2009<\/jats:italic>&lt;\u20090.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CTC dynamics during therapy are associated with PSA response and provide independent clinical prognostication over PSA declines. Hence the study demonstrates the pharmacodynamic properties of CTCs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.23488","type":"journal-article","created":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T12:03:14Z","timestamp":1518436994000},"page":"435-445","source":"Crossref","is-referenced-by-count":23,"title":["Circulating tumor cells and survival in abiraterone\u2010 and enzalutamide\u2010treated patients with castration\u2010resistant prostate cancer"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1174-0384","authenticated-orcid":false,"given":"Bram","family":"De Laere","sequence":"first","affiliation":[{"name":"Center for Oncological Research (CORE) University of Antwerp Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffi","family":"Oeyen","sequence":"additional","affiliation":[{"name":"Center for Oncological Research (CORE) University of Antwerp Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Van Oyen","sequence":"additional","affiliation":[{"name":"Department of Urology AZ Sint\u2010Jan Brugge\u2010Oostende AV Brugge Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Ghysel","sequence":"additional","affiliation":[{"name":"Department of Urology AZ Sint\u2010Jan Brugge\u2010Oostende AV Brugge Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jozef","family":"Ampe","sequence":"additional","affiliation":[{"name":"Department of Urology AZ Sint\u2010Jan Brugge\u2010Oostende AV Brugge Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piet","family":"Ost","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Ghent University Hospital Ghent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wim","family":"Demey","sequence":"additional","affiliation":[{"name":"Department of Oncology AZ KLINA Brasschaat Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucien","family":"Hoekx","sequence":"additional","affiliation":[{"name":"Department of Urology Antwerp University Hospital Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Schrijvers","sequence":"additional","affiliation":[{"name":"Department of Oncology ZNA Middelheim Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Brouwers","sequence":"additional","affiliation":[{"name":"Department of Oncology AZ Sint\u2010Jan Brugge\u2010Oostende AV Brugge Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willem","family":"Lybaert","sequence":"additional","affiliation":[{"name":"Department of Oncology AZ Nikolaas Sint\u2010Niklaas Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Els","family":"Everaert","sequence":"additional","affiliation":[{"name":"Department of Oncology AZ Nikolaas Sint\u2010Niklaas Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piet","family":"Van Kerckhove","sequence":"additional","affiliation":[{"name":"Department of Oncology AZ Sint\u2010Jan Brugge\u2010Oostende AV Brugge Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daan","family":"De Maeseneer","sequence":"additional","affiliation":[{"name":"Department of Oncology AZ Sint\u2010Lucas Brugge Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiel","family":"Strijbos","sequence":"additional","affiliation":[{"name":"Department of Oncology AZ KLINA Brasschaat Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Bols","sequence":"additional","affiliation":[{"name":"Department of Oncology AZ Sint\u2010Jan Brugge\u2010Oostende AV Brugge Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Fransis","sequence":"additional","affiliation":[{"name":"Department of Urology Antwerp University Hospital Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nick","family":"Beije","sequence":"additional","affiliation":[{"name":"Department of Oncology Erasmus MC Cancer Institute Rotterdam Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inge","family":"de Kruijff","sequence":"additional","affiliation":[{"name":"Department of Oncology Erasmus MC Cancer Institute Rotterdam Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie","family":"van Dam","sequence":"additional","affiliation":[{"name":"Center for Oncological Research (CORE) University of Antwerp Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Center for Oncological Research (CORE) University of Antwerp Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter\u2010Jan","family":"van Dam","sequence":"additional","affiliation":[{"name":"Center for Oncological Research (CORE) University of Antwerp Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gert","family":"Van den Eynden","sequence":"additional","affiliation":[{"name":"Center for Oncological Research (CORE) University of Antwerp Antwerp Belgium"},{"name":"Department of Pathology GZA Hospitals Sint\u2010Augustinus Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemie","family":"Rutten","sequence":"additional","affiliation":[{"name":"Department of Oncology GZA Hospitals Sint\u2010Augustinus Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Sleijfer","sequence":"additional","affiliation":[{"name":"Department of Oncology Erasmus MC Cancer Institute Rotterdam Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Vandebroek","sequence":"additional","affiliation":[{"name":"Department of Oncology GZA Hospitals Sint\u2010Augustinus Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Van Laere","sequence":"additional","affiliation":[{"name":"Center for Oncological Research (CORE) University of Antwerp Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc","family":"Dirix","sequence":"additional","affiliation":[{"name":"Center for Oncological Research (CORE) University of Antwerp Antwerp Belgium"},{"name":"Department of Oncology GZA Hospitals Sint\u2010Augustinus Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,2,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2012.12.027"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2011.02799.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.11.010"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1014618"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209096"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1405095"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1207506"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201303701"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.001"},{"key":"e_1_2_8_11_1","first-page":"707","article-title":"Clinical phenotypes of castration\u2010resistant prostate cancer","volume":"11","author":"Zhang T","year":"2013","journal-title":"Clin Adv Hematol Oncol"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0872"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.55.3487"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.4487"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040766"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.8923"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1506"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdn544"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-08-1173"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(08)70340-1"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2011.07.011"},{"key":"e_1_2_8_22_1","doi-asserted-by":"crossref","first-page":"5026","DOI":"10.1200\/jco.2013.31.15_suppl.5026","article-title":"An exploratory analysis of bone scan lesion area (BSLA), circulating tumor cell (CTC) change, pain reduction, and overall survival (OS) in patients (pts) with castration\u2010resistant prostate cancer (CRPC) treated with cabozantinib (cabo): updated results of a phase II nonrandomized expansion (NRE) cohort","volume":"31","author":"Scher HI","year":"2013","journal-title":"J Clin Oncol"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.54.5954"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-013-1377-5"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.51.7417"},{"key":"e_1_2_8_26_1","first-page":"6705","article-title":"Circulating tumor cells as a biomarker predictive of sensitivity to docetaxel chemotherapy in patients with castration\u2010resistant prostate cancer","volume":"34","author":"Okegawa T","year":"2014","journal-title":"Anticancer Res"},{"key":"e_1_2_8_27_1","doi-asserted-by":"crossref","first-page":"5035","DOI":"10.1200\/jco.2015.33.15_suppl.5035","article-title":"Circulating tumor cell (CTC) enumeration in men with metastatic castration\u2010resistant prostate cancer (mCRPC) treated with enzalutamide post\u2010chemotherapy (phase 3 AFFIRM study)","volume":"33","author":"Fleisher M","year":"2015","journal-title":"J Clin Oncol"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-015-1936-z"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2014.09.002"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2016.07.051"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2016.05.023"},{"key":"e_1_2_8_32_1","first-page":"299","article-title":"Circulating tumor cell number as a response measure of prolonged survival for metastatic castration\u2010Resistant prostate cancer: a comparison with prostate\u2010Specific antigen across five randomized phase III clinical trials","volume":"75","author":"Heller G","year":"2017","journal-title":"J Clin Oncol"},{"key":"e_1_2_8_33_1","first-page":"548","article-title":"Circulating tumor cell eradication as an intermediate efficacy end point for metastatic castration\u2010Resistant prostate cancer: is there enough evidence","volume":"76","author":"Antonarakis ES","year":"2017","journal-title":"J Clin Oncol"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2015.63"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep12270"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.13631"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-1353"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpros.23488","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.23488","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T12:26:20Z","timestamp":1695644780000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.23488"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,12]]},"references-count":36,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1002\/pros.23488"],"URL":"https:\/\/doi.org\/10.1002\/pros.23488","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,12]]}}}