{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:54:41Z","timestamp":1790362481320,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Apalutamide treatment for prostate cancer may require discontinuation because of adverse events, particularly rashes. We evaluated the real-world outcomes of switching to other androgen receptor signaling inhibitors (ARSI) following such discontinuations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter retrospective cohort study included men with metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant prostate cancer (nmCRPC) who received apalutamide between July 2019 and August 2025. Those who discontinued apalutamide comprised the switch group. We noted the reasons for discontinuation and compared progression-free survival (PFS) or metastasis-free survival (MFS) and overall survival (OS) between the switch and no-switch groups by disease category. Rash recurrence after switching was also assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 117 total patients, 17 (14.5%) comprised the switch group. Rashes accounted for all of the discontinuations, with 40% being grades \u22653. PFS and OS did not differ significantly between the switch and non-switch patients with mCSPC (log-rank P\u00a0=\u00a0.548 and P\u00a0=\u00a0.785, respectively), and similar MFS and OS results were observed in those with nmCRPC (P\u00a0=\u00a0.674 and P\u00a0=\u00a0.861, respectively). The rashes recurred after switching to alternative therapies in 5.8% (n\u00a0=\u00a01) of the patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This real-world multicenter analysis demonstrated that approximately one in seven patients with prostate cancer discontinued apalutamide treatment because they developed rashes. However, switching to other ARSIs preserved oncological outcomes, with no significant differences in PFS, MFS, or OS observed, regardless of prostate cancer subtype. Therefore, this type of switching does not appear to compromise subsequent treatment efficacy if it is done while the disease remains sensitive to ARSIs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jjco\/hyaf205","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T12:54:17Z","timestamp":1765284857000},"page":"345-351","source":"Crossref","is-referenced-by-count":1,"title":["Real-world efficacy of switching androgen receptor signaling inhibitor therapy following apalutamide discontinuation because of adverse events in advanced prostate cancer: a multicenter study"],"prefix":"10.1093","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3884-8915","authenticated-orcid":false,"given":"Yoichiro","family":"Tohi","sequence":"first","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Kagawa University , 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2047-496X","authenticated-orcid":false,"given":"Takuma","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Kagawa University , 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kengo","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Kagawa University , 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushi","family":"Hayashida","sequence":"additional","affiliation":[{"name":"Department of Urology, Sakaide City Hospital , 3-1-2 Kotobuki-cho, Sakaide-shi, Kagawa 762-8550 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Department of Urology, KKR Takamatsu Hospital , 4-18 Tenjinmae, Takamatsu-shi, Kagawa 760-0018 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Hirama","sequence":"additional","affiliation":[{"name":"Department of Urology, KKR Takamatsu Hospital , 4-18 Tenjinmae, Takamatsu-shi, Kagawa 760-0018 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Urology, Shodoshima Central Hospital , 2060-1 Ikeda, Shodoshima-cho, Shozu-gun, Kagawa 761-4301 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Tsunemori","sequence":"additional","affiliation":[{"name":"Department of Urology, Takinomiya General Hospital , 486 Takinomiya, Ayagawa-cho, Ayauta-gun, Kagawa 761-2305 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironobu","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Urology, Mizushima Kyodo Hospital , 1-1 Mizushima-minami Kasuga-cho, Kurashiki-shi, Okayama 712-8567 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaku","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Urology, Kinashi Obayashi Hospital , 435-1 Kinashi-cho, Takamatsu-shi, Kagawa 761-8024 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyoshi","family":"Yamaoka","sequence":"additional","affiliation":[{"name":"Department of Urology, Kagawa Prefectural Shirotori Hospital , 963 Matsubara, Higashikagawa-shi, Kagawa 769-2788 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Mashima","sequence":"additional","affiliation":[{"name":"Department of Urology, Yashima General Hospital , 2105-17 Yashima Nishimachi, Takamatsu-shi, Kagawa 761-0186 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Kohashiguchi","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Kagawa University , 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Kagawa University , 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1045-1978","authenticated-orcid":false,"given":"Hirohito","family":"Naito","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Kagawa University , 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Homare","family":"Okazoe","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Kagawa University , 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikiya","family":"Taoka","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Kagawa University , 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobufumi","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Kagawa University , 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9266-782X","authenticated-orcid":false,"given":"Mikio","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Kagawa University , 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"key":"2026060811215794600_ref1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1056\/NEJMoa1903307","article-title":"Apalutamide for metastatic, castration-sensitive prostate cancer","volume":"381","author":"Chi","year":"2019","journal-title":"N Engl J Med"},{"key":"2026060811215794600_ref2","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.eururo.2020.08.011","article-title":"Apalutamide and overall survival in prostate cancer","volume":"79","author":"Smith","year":"2021","journal-title":"Eur Urol"},{"key":"2026060811215794600_ref3","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.eururo.2024.04.010","article-title":"EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on prostate cancer. Part II-2024 update: treatment of relapsing and metastatic prostate cancer","volume":"86","author":"Tilki","year":"2024","journal-title":"Eur Urol"},{"key":"2026060811215794600_ref4","doi-asserted-by":"publisher","year":"2026","DOI":"10.1111\/bcpt.70176"},{"key":"2026060811215794600_ref5","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1111\/iju.15545","article-title":"Japanese clinical practice guidelines for prostate cancer 2023","volume":"31","author":"Kohjimoto","year":"2024","journal-title":"Int J Urol"},{"key":"2026060811215794600_ref6","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1093\/jjco\/hyaf025","article-title":"Real-world clinical usage and efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer: a multi-institutional study in the CsJUC","volume":"55","author":"Tohi","year":"2025","journal-title":"Jpn J Clin Oncol"},{"key":"2026060811215794600_ref7","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/j.euo.2023.12.013","article-title":"Clinical outcomes of patients with high-risk metastatic hormone-na\u00efve prostate cancer: a 3-year interim analysis of the observational J-ROCK Study","volume":"7","author":"Miyake","year":"2024","journal-title":"Eur Urol Oncol"},{"key":"2026060811215794600_ref8","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1093\/jjco\/hyad143","article-title":"Real-world prostate-specific antigen response and progression to castration-resistant prostate cancer among men with metastatic castration-sensitive prostate cancer treated with apalutamide: a multi-institutional study in the Chu-Shikoku Japan Urological Consortium","volume":"54","author":"Tohi","year":"2024","journal-title":"Jpn J Clin Oncol"},{"key":"2026060811215794600_ref9","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1186\/s12894-020-00689-0","article-title":"Skin rash following Administration of Apalutamide in Japanese patients with advanced prostate cancer: an integrated analysis of the phase 3 Spartan and Titan studies and a phase 1 open-label study","volume":"20","author":"Uemura","year":"2020","journal-title":"BMC Urol"},{"key":"2026060811215794600_ref10","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1002\/pros.24453","article-title":"Effects of apalutamide dose reduction on skin-related adverse events in patients with advanced prostate cancer: a multicenter retrospective study","volume":"83","author":"Oishi","year":"2023","journal-title":"Prostate"},{"key":"2026060811215794600_ref11","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.21873\/anticanres.15682","article-title":"Low body weight as a risk factor for apalutamide-related cutaneous adverse events","volume":"42","author":"Katsuta","year":"2022","journal-title":"Anticancer Res"},{"key":"2026060811215794600_ref12","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1007\/s10147-022-02183-z","article-title":"Real-world analysis of apalutamide-associated skin adverse events in Japanese patients with advanced prostate cancer: a multi-institutional study in the Chu-Shikoku Japan Urological Consortium","volume":"27","author":"Tohi","year":"2022","journal-title":"Int J Clin Oncol"},{"key":"2026060811215794600_ref13","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1093\/jjco\/hyaf082","article-title":"Skin rash induced by apalutamide correlated with age and relative dose intensity adjusted by body surface area in Japanese patients with prostate cancer","volume":"55","author":"Akagi","year":"2025","journal-title":"Jpn J Clin Oncol"},{"key":"2026060811215794600_ref14","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1111\/iju.13137","article-title":"Androgen receptor targeted therapies in castration-resistant prostate cancer: bench to clinic","volume":"23","author":"Imamura","year":"2016","journal-title":"Int J Urol"},{"key":"2026060811215794600_ref15","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1056\/NEJMoa1815671","article-title":"Darolutamide in nonmetastatic, castration-resistant prostate cancer","volume":"380","author":"Fizazi","year":"2019","journal-title":"N Engl J Med"},{"key":"2026060811215794600_ref16","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1200\/JCO.2017.75.3657","article-title":"Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial","volume":"36","author":"Kyriakopoulos","year":"2018","journal-title":"J Clin Oncol"},{"key":"2026060811215794600_ref17","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1200\/JCO.2007.12.4487","article-title":"Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the prostate cancer clinical trials working group","volume":"26","author":"Scher","year":"2008","journal-title":"J Clin Oncol"},{"key":"2026060811215794600_ref18","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation of the freely available easy-to-use software \u2018EZR\u2019 for medical statistics","volume":"48","author":"Kanda","year":"2013","journal-title":"Bone Marrow Transplant"},{"key":"2026060811215794600_ref19","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1158\/1535-7163.MCT-20-0015","article-title":"Cross-resistance among next-generation antiandrogen drugs through the AKR1C3\/AR-V7 axis in advanced prostate cancer","volume":"19","author":"Zhao","year":"2020","journal-title":"Mol Cancer Ther"},{"key":"2026060811215794600_ref20","doi-asserted-by":"publisher","first-page":"3176","DOI":"10.1002\/cam4.5189","article-title":"Sequential therapy with darolutamide in patients with non-metastatic castration-resistant prostate cancer resistant to enzalutamide or apalutamide","volume":"12","author":"Fujmoto","year":"2023","journal-title":"Cancer Med"},{"key":"2026060811215794600_ref21","doi-asserted-by":"publisher","first-page":"2974","DOI":"10.1200\/JCO.19.00799","article-title":"ARCHES: a randomized, Phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer","volume":"37","author":"Armstrong","year":"2019","journal-title":"J Clin Oncol"},{"key":"2026060811215794600_ref22","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1093\/oncolo\/oyae019","article-title":"Extended safety and tolerability of darolutamide for nonmetastatic castration-resistant prostate cancer and adverse event time course in ARAMIS","volume":"29","author":"Shore","year":"2024","journal-title":"Oncologist"},{"key":"2026060811215794600_ref23","doi-asserted-by":"publisher","first-page":"161","DOI":"10.4103\/aja.aja_64_21","article-title":"Apalutamide for patients with metastatic castration-sensitive prostate cancer in East Asia: a subgroup analysis of the TITAN trial","volume":"24","author":"Chung","year":"2022","journal-title":"Asian J Androl"},{"key":"2026060811215794600_ref24","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1111\/iju.15587","article-title":"Management of apalutamide-induced rash with focus on early peaks","volume":"32","author":"Hashimoto","year":"2025","journal-title":"Int J Urol"},{"key":"2026060811215794600_ref25","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1038\/s41391-024-00858-4","article-title":"Impact of a rash management guide in patients receiving apalutamide for high-risk localized prostate cancer in the Apa-RP study","volume":"28","author":"Shore","year":"2025","journal-title":"Prostate Cancer Prostatic Dis"}],"container-title":["Japanese Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jjco\/article-pdf\/56\/3\/345\/66128029\/hyaf205.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jjco\/article-pdf\/56\/3\/345\/66128029\/hyaf205.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T15:22:05Z","timestamp":1780932125000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jjco\/article\/56\/3\/345\/8404857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,26]]},"references-count":25,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,12,26]]},"published-print":{"date-parts":[[2026,3,13]]}},"URL":"https:\/\/doi.org\/10.1093\/jjco\/hyaf205","relation":{},"ISSN":["1465-3621"],"issn-type":[{"value":"1465-3621","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2025,12,26]]}}}