{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:01:46Z","timestamp":1780470106838,"version":"3.54.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"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. Pharmacol."],"abstract":"<jats:p>Locally advanced prostate cancer (LAPC) is associated with a higher risk of recurrence and metastasis. Perioperative intensified systemic therapy may contribute to tumor downstaging. However, clinical evidence supporting darolutamide-based treatment in LAPC remains limited, and biomarker-informed treatment in this setting is not well established. We report the case of a 70-year-old man with cT4N1M0 LAPC without PTEN or RB1 loss by immunohistochemistry (IHC). At presentation, the patient\u2019s total prostate-specific antigen (TPSA) level was 88.80\u00a0ng\/mL. Prostate multiparametric magnetic resonance imaging (mpMRI) revealed the invasion of right lateral bladder wall, bladder neck and bilateral seminal vesicles, and enlarged pelvic lymph nodes. Conventional imaging, including bone scintigraphy and computed tomography showed no evidence of distant metastasis. Transperineal prostate biopsy confirmed prostatic acinar adenocarcinoma with a Gleason score of 5 + 4 = 9 (ISUP Grade Group 5). The initial intensified systemic regimen is the doublet therapy of Darolutamide (600\u00a0mg orally twice daily) and goserelin (10.8\u00a0mg administered subcutaneously every 3\u00a0months). Castration-level testosterone was achieved after 1 month, and TPSA decreased sharply from 88.80\u00a0ng\/mL to 0.15\u00a0ng\/mL at month 1 and 0.008\u00a0ng\/mL at month 8. After 8 months of doublet therapy, follow-up mpMRI showed no residual suspicious lesion or enlarged pelvic lymph nodes. As a tailored local consolidation strategy, the patient underwent laparoscopic radical prostatectomy (LRP) and pelvic lymph node dissection after MDT discussion. A pathological complete response (pCR) was achieved, as confirmed by postoperative pathology showing no residual tumor in the prostatectomy specimen or pelvic lymph nodes (ypT0N0). The recovery of urinary incontinence was achieved after 2\u00a0months following LRP, while Darolutamide plus ADT was continued postoperatively. During 20 months of follow-up, the patient maintained an undetectable PSA, and had no radiographic evidence of disease relapse with well treatment tolerance. This case suggests that darolutamide plus ADT, administered as a tailored perioperative intensified systemic strategy, may induce a rapid and profound PSA response and may be associated with pCR in selected patients with very high-risk LAPC, while further investigation is warranted.<\/jats:p>","DOI":"10.3389\/fphar.2026.1829605","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:05:21Z","timestamp":1780466721000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pathological complete response to perioperative treatment with darolutamide plus ADT in locally advanced prostate cancer without PTEN or RB1 loss: a case report"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhihui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwei","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qimei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]},{"name":"Central Sterile Supply Department, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhu","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Kan","sequence":"additional","affiliation":[{"name":"Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhao","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxiao","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.ccr.2011.04.008","article-title":"Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer","volume":"19","author":"Carver","year":"2011","journal-title":"Cancer Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"254","DOI":"10.2165\/00003495-199141020-00008","article-title":"Goserelin. 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