{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T16:34:22Z","timestamp":1776184462268,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2020,9,19]],"date-time":"2020-09-19T00:00:00Z","timestamp":1600473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA208254\u201001"],"award-info":[{"award-number":["R01CA208254\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U10CA180820"],"award-info":[{"award-number":["U10CA180820"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U10CA180794"],"award-info":[{"award-number":["U10CA180794"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UG1CA233180"],"award-info":[{"award-number":["UG1CA233180"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UG1CA233196"],"award-info":[{"award-number":["UG1CA233196"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The immunosuppressive cytokine interleukin\u2010 8 (IL\u20108), produced by tumor cells and some myeloid cells, promotes inflammation, angiogenesis, and metastasis. In our discovery work, elevated serum IL\u20108 at androgen deprivation therapy (ADT) initiation portended worse overall survival (OS). Leveraging serum samples from the phase 3 CHAARTED trial of patients treated with ADT\u2009+\/\u2212\u2009docetaxel for metastatic hormone\u2010sensitive prostate cancer (mHSPC), we validated these findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two hundred and thirty\u2010three patients had serum samples drawn within 28 days of ADT initiation. The samples were assayed using the same Mesoscale Multiplex ELISA platform employed in the discovery cohort. After adjusting for performance status, disease volume, and de novo\/metachronous metastases, multivariable Cox proportional hazards models assessed associations between IL\u20108 as continuous and binary variables on OS and time to castration\u2010resistant prostate cancer (CRPC). The median IL\u20108 level (9.3\u2009pg\/ml) was the a priori binary cutpoint. Fixed\u2010effects meta\u2010analyses of the discovery and validation sets were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Higher IL\u20108 levels were prognostic for shorter OS (continuous: hazard ratio [HR]\u00a02.2, 95% confidence interval [CI]: 1.4\u20133.6, <jats:italic>p<\/jats:italic>\u2009=\u2009.001; binary &gt;9.3: HR 1.7, 95% CI: 1.2\u20132.4, <jats:italic>p<\/jats:italic>\u2009=\u2009.007) and time to CRPC (continuous: HR\u00a02.3, 95% CI: 1.6\u20133.3, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001; binary: HR 1.8, 95% CI: 1.3\u20132.5, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001) and independent of docetaxel use, disease burden, and time of metastases. Meta\u2010analysis including the discovery cohort, also showed that binary IL\u20108 levels &gt;9.3\u2009pg\/ml from patients treated with ADT alone was prognostic for poorer OS (HR\u00a01.8, 95% CI: 1.2\u20132.7, <jats:italic>p<\/jats:italic>\u2009=\u2009.007) and shorter time to CRPC (HR\u00a01.4, 95% CI: 0.99\u20131.9, <jats:italic>p<\/jats:italic>\u2009=\u2009.057).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In the phase 3 CHAARTED study of men with mHSPC at ADT initiation, elevated IL\u20108 portended worse survival and shorter time to castration\u2010resistant prostate cancer independent of docetaxel administration, metastatic burden, and metachronous versus de novo metastatic presentation. These findings support targeting IL\u20108 as a strategy to improve mHSPC outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24074","type":"journal-article","created":{"date-parts":[[2020,9,19]],"date-time":"2020-09-19T12:30:26Z","timestamp":1600518626000},"page":"1429-1437","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Impact of baseline serum IL\u20108 on metastatic hormone\u2010sensitive prostate cancer outcomes in the Phase 3 CHAARTED trial (E3805)"],"prefix":"10.1002","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7636-1588","authenticated-orcid":false,"given":"Lauren C.","family":"Harshman","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Dana\u2010Farber Cancer Institute, Lank Center for Genitourinary Oncology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria X.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Data Science Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anis A.","family":"Hamid","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana\u2010Farber Cancer Institute, Lank Center for Genitourinary Oncology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Santone","sequence":"additional","affiliation":[{"name":"Department of Medicine Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9610-3677","authenticated-orcid":false,"given":"Charles G.","family":"Drake","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Oncology, Herbert Irving Comprehensive Cancer Center Columbia University Medical Center  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Carducci","sequence":"additional","affiliation":[{"name":"Department of Oncology Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert S.","family":"DiPaola","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Kentucky College of Medicine  Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raina N.","family":"Fichorova","sequence":"additional","affiliation":[{"name":"Department of Medicine Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J.","family":"Sweeney","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana\u2010Farber Cancer Institute, Lank Center for Genitourinary Oncology 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