{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:59:16Z","timestamp":1790035156845,"version":"4.0.1"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Prostate cancer ranks as the second most prevalent cancer among men, with androgen deprivation therapy (ADT) being a cornerstone treatment strategy. Enzalutamide, apalutamide, and darolutamide are key examples of second-generation androgen receptor antagonists (SGARAs). Although severe cutaneous adverse reactions (SCARs) are infrequent, they carry a significant risk of mortality. This study employed four disproportionality analysis algorithms: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) to investigate the potential link between SGARAs and SCARs. As of the second quarter of 2024, reports of SCARs related to enzalutamide, apalutamide, and darolutamide totaled 25, 77, and 1, respectively. The majority of reports came from elderly patients, predominantly reported by health professionals, with Japan and the USA being the primary reporting countries. SCARs related to apalutamide detected positive signals in all four algorithms, while enzalutamide and darolutamide did not show positive signals. The study indicated that the majority of onset times occurred within 37 days, but SCARs could still occur up to 176 days with enzalutamide and 126 days after apalutamide treatment. No onset time was reported for darolutamide. In the treatment of prostate cancer with SGARAs, there is a potential risk of SCARs. When different SGARAs were compared, SCARs were more frequently reported with apalutamide than enzalutamide and darolutamide. This indicates that patients using SGARAs, particularly apalutamide, require closer and more prolonged monitoring to facilitate the early detection and management of SCARs and to reduce the occurrence of serious outcomes.<\/jats:p>","DOI":"10.1371\/journal.pone.0325448","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T17:36:12Z","timestamp":1749576972000},"page":"e0325448","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Severe cutaneous adverse reactions associated with second-generation androgen receptor antagonists in prostate cancer patients"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7113-9374","authenticated-orcid":true,"given":"Junfa","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongfei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8563-2247","authenticated-orcid":true,"given":"Zhitao","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"issue":"3","key":"pone.0325448.ref001","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"F Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"issue":"10437","key":"pone.0325448.ref002","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1016\/S0140-6736(24)00651-2","article-title":"The Lancet Commission on prostate cancer: planning for the surge in cases","volume":"403","author":"ND James","year":"2024","journal-title":"Lancet"},{"key":"pone.0325448.ref003","article-title":"Prostate Cancer in Seniors: Part 1: Epidemiology, Pathology, and Screening","volume":"32","author":"HW Chin","year":"2015","journal-title":"Fed Pract"},{"issue":"1","key":"pone.0325448.ref004","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/annonc\/mdr056","article-title":"Risk for incident and fatal prostate cancer in men with a family history of any incident and fatal cancer","volume":"23","author":"A Brandt","year":"2012","journal-title":"Ann Oncol"},{"issue":"2","key":"pone.0325448.ref005","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.eururo.2021.12.011","article-title":"Defining the Impact of Family History on Detection of High-grade Prostate Cancer in a Large Multi-institutional Cohort","volume":"82","author":"MB Clements","year":"2022","journal-title":"Eur Urol"},{"issue":"7","key":"pone.0325448.ref006","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1038\/s41416-021-01675-5","article-title":"BRCA1 and BRCA2 pathogenic variants and prostate cancer risk: systematic review and meta-analysis","volume":"126","author":"T Nyberg","year":"2022","journal-title":"Br J Cancer"},{"issue":"1","key":"pone.0325448.ref007","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41436-019-0596-9","article-title":"Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database","volume":"22","author":"M Dominguez-Valentin","year":"2020","journal-title":"Genet Med"},{"issue":"6","key":"pone.0325448.ref008","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.euo.2021.09.006","article-title":"Epidemiology and Prevention of Prostate Cancer","volume":"4","author":"G Gandaglia","year":"2021","journal-title":"Eur Urol Oncol"},{"key":"pone.0325448.ref009","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/S0022-5347(02)80307-X","article-title":"Studies on prostatic cancer. 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