{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:00:31Z","timestamp":1770746431841,"version":"3.49.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Contemporary guidelines recommend docetaxel as first-line chemotherapy for chemotherapy-na\u00efve men with metastatic castration-resistant prostate cancer (mCRPC) who progress on an androgen receptor signaling inhibitor (ARSI). Cabazitaxel is preferred after prior docetaxel and one ARSI. However, real-world constraints\u2014such as patient preference, access, or comorbidity\u2014often preclude chemotherapy, and cross-resistance among ARSIs is common, making robust responses to same-agent rechallenge uncommon. We report a 74-year-old man diagnosed in 2015 with\n                    <jats:italic>de novo<\/jats:italic>\n                    metastatic hormone-sensitive prostate cancer (Gleason 4 + 4; cT4N1M1b). Under continuous medical castration, he received sequential first- and next-generation ARSIs but consistently declined chemotherapy and radiotherapy. Following biochemical progression on enzalutamide in early 2025, which was accompanied by imaging findings suggestive of a new T12 lesion, and after a brief bicalutamide interval, enzalutamide was rechallenged under a time-limited, PCWG3-aligned protocol with predefined stop rules. Over five months, prostate-specific antigen (PSA) levels declined from 17.73 ng\/mL to 2.62 ng\/mL (~85% reduction); this PSA response was maintained for \u22655 months through the last follow-up while the patient remained on enzalutamide, without new adverse events or increased analgesic use. This case suggests that in a preference-constrained, chemotherapy-na\u00efve patient, same-agent enzalutamide rechallenge can yield a clinically meaningful PSA response. The observation raises the hypothesis that ARSI resistance may be reversible in a subset of patients, warranting prospective evaluation of biomarker-guided rechallenge strategies to optimize patient selection and minimize opportunity cost.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1759642","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T05:22:02Z","timestamp":1770700922000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Deep and durable PSA response to same-agent enzalutamide rechallenge in metastatic castration-resistant prostate cancer without chemotherapy"],"prefix":"10.3389","volume":"16","author":[{"given":"Huan","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Qu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1207506","article-title":"Increased survival with enzalutamide in prostate cancer after chemotherapy","volume":"367","author":"Scher","year":"2012","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1056\/NEJMoa1014618","article-title":"Abiraterone and 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