{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T14:16:50Z","timestamp":1788617810490,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008897","name":"Janssen Pharmaceutica","doi-asserted-by":"publisher","award":["56021927PCR4013"],"award-info":[{"award-number":["56021927PCR4013"]}],"id":[{"id":"10.13039\/100008897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Despite promising evidence of the efficacy of the androgen deprivation therapy (ADT) plus apalutamide in metastatic castration\u2010sensitive prostate cancer (mCSPC), it remains unknown how its effectiveness and safety are shaped by genetic factors, particularly among Asian populations. We evaluated whether baseline circulating tumor deoxyribonucleic acid (ctDNA) and germline variants predict outcomes and tolerability in the phase IV, open label, multicenter CUARTET trial in Japan. We enrolled 101 patients with mCSPC starting apalutamide with ADT; 99 contributed pretreatment plasma for ctDNA profiling across 73 prostate cancer driver genes and 86 provided genome\u2010wide single nucleotide polymorphism (SNP) data. Primary endpoints were time to castration resistant prostate cancer (CRPC) and overall survival; skin rash incidence was assessed as a key adverse event. Cox models (adjusted for volume of disease) and exploratory machine\u2010learning\u2013assisted logistic regression were applied. ctDNA presence at baseline was associated with shorter time to CRPC (adjusted hazard ratio [HR] 3.18; 95% confidence interval [CI], 1.17\u201311.09) and overall survival (adjusted HR for all\u2010cause mortality 3.95; 95% CI, 1.06\u201325.63). Among 55 paired samples, ctDNA presence increased from 61.8% pretreatment to 87.2% posttreatment, and alterations in androgen receptor and DNA repair pathways were enriched in patients who discontinued for progression. Any grade skin rash occurred in 59.4% and grade\u2009\u2265\u20093 in 5.9%. An exploratory genome\u2010wide screen identified 12 SNPs associated with skin rash. This study demonstrated that baseline ctDNA predicts prognosis of Japanese patients with mCSPC receiving apalutamide with ADT and identified potential genetic predictors for treatment\u2010related skin rash.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/\">ClinicalTrials.gov<\/jats:ext-link>\n                    identifier: jRCTs071200040\n                  <\/jats:p>","DOI":"10.1111\/cas.70401","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T04:43:52Z","timestamp":1777437832000},"page":"1985-1995","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Predictors of Progression and Skin Rash in Japanese\n                    <scp>mCSPC<\/scp>\n                    Patients Treated With Apalutamide:\n                    <scp>CUARTET<\/scp>\n                    Study"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3306-4858","authenticated-orcid":false,"given":"Masaki","family":"Shiota","sequence":"first","affiliation":[{"name":"Department of Urology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7638-6048","authenticated-orcid":false,"given":"Taku","family":"Naiki","sequence":"additional","affiliation":[{"name":"Department of Nephro\u2010Urology Nagoya City University Graduate School of Medical Sciences  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Hatano","sequence":"additional","affiliation":[{"name":"Department of Urology The University of Osaka Graduate School of Medicine  Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5741-6280","authenticated-orcid":false,"given":"Akira","family":"Yokomizo","sequence":"additional","affiliation":[{"name":"Department of Urology Harasanshin Hospital  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Medical Affairs Department J&amp;J Innovative Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Medical Affairs Operations, Global Development, Johnson &amp; Johnson  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Medical Affairs, Oncology Group, Johnson &amp; Johnson  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Medical Affairs, Oncology Group, Johnson &amp; Johnson  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3665-9523","authenticated-orcid":false,"given":"Hirotsugu","family":"Uemura","sequence":"additional","affiliation":[{"name":"Kindai University Faculty of Medicine  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.75.3657"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.0591"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-3948"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1903307"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.03488"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.14843"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevOncog.2022043298"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2018.12.042"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-024-03294-8"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.2702"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euros.2025.05.001"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.16449"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1503747"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44276-024-00093-3"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.7051"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euros.2024.10.008"},{"issue":"25","key":"e_1_2_12_18_1","first-page":"864","article-title":"Tumor Transcriptome\u2010Wide Expression Classifiers Predict Treatment Sensitivity in Advanced Prostate Cancers","volume":"0092","author":"Grist E.","year":"2025","journal-title":"Cell"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26115309"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201025\u20101178"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.05.534"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/02770903.2019.1666867"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70401","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.70401","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70401","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T14:10:13Z","timestamp":1788617413000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.70401"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,28]]},"references-count":21,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/cas.70401"],"URL":"https:\/\/doi.org\/10.1111\/cas.70401","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,28]]},"assertion":[{"value":"2026-01-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}