{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T15:54:22Z","timestamp":1771257262297,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004948","name":"Astellas Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004948","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate the longitudinal transcriptomic changes that occurred over time in patients from the ENACT trial (ClinicalTrials.gov identifier: NCT02799745). ENACT evaluated patients with low\u2010 or intermediate\u2010risk prostate cancer, comparing the efficacy and safety of enzalutamide plus active surveillance (AS) to AS alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>Gene\u2010expression profiling was conducted using the Decipher Genomic Resource for Intelligent Discovery (GRID) platform (Veracyte, Inc.) on 131 patient samples (enzalutamide plus AS: <jats:italic>n<\/jats:italic>\u2009=\u200957; AS alone: <jats:italic>n<\/jats:italic>\u2009=\u200974) collected at screening, Year 1, and Year 2. Pre\u2010defined GRID signatures were analysed for associations with biological and clinical features, including immune activity, treatment sensitivity, metastatic risk, and molecular subtypes. Statistical analyses utilised Cox proportional hazards models and logistic\/linear regression, while longitudinal changes were evaluated using linear mixed\u2010effects models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At Year 1, patients treated with enzalutamide plus AS showed significant transcriptomic changes, such as downregulation of androgen\u2010receptor signalling and immune\u2010suppressor signatures, alongside upregulation of immune\u2010activated and basal\u2010like markers. Many of these transcriptomic alterations, including immune\u2010related changes, were transient and reverted to baseline levels at Year 2 after enzalutamide treatment cessation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This exploratory biomarker analysis highlights transcriptomic changes in patients undergoing AS and those treated with enzalutamide, providing insights into molecular disease progression on surveillance and the effects of transient exposure to enzalutamide. The observed immune modulation during enzalutamide treatment suggests opportunities to explore immunotherapy strategies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bju.16861","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T12:14:34Z","timestamp":1753964074000},"page":"920-929","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptome profiling of prostatic tumours from ENACT trial patients with or without enzalutamide"],"prefix":"10.1111","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0700-7200","authenticated-orcid":false,"given":"Nicole","family":"Handa","sequence":"first","affiliation":[{"name":"Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neal D.","family":"Shore","sequence":"additional","affiliation":[{"name":"Carolina Urologic Research Center  Myrtle Beach SC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4339-6685","authenticated-orcid":false,"given":"Matthew R.","family":"Cooperberg","sequence":"additional","affiliation":[{"name":"Urology and Epidemiology &amp; Biostatistics, UCSF Helen Diller Comprehensive Cancer Center  San Francisco CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elai","family":"Davicioni","sequence":"additional","affiliation":[{"name":"Veracyte, Inc.  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