{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T22:00:15Z","timestamp":1770242415172,"version":"3.49.0"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: The National Comprehensive Cancer Network (NCCN) classifies prostate cancer with PSA &gt; 20 ng\/mL as high risk; however, outcomes within this group are heterogeneous. Emerging data suggest that men with PSA &gt; 20 ng\/mL as the sole high-risk feature may have more favorable disease biology. We evaluated outcomes of men with prostate cancer treated with definitive radiation therapy (RT), focusing on the prognostic significance of individual high-risk factors. Methods: We analyzed 742 men with prostatic adenocarcinoma treated with curative-intent RT between 2005 and 2021, including 282 meeting traditional NCCN high-risk criteria. Treatment consisted of dose-escalated RT (median 78 Gy), with androgen deprivation therapy (ADT) administered to 94% (median duration 28 months). Primary endpoints were freedom from biochemical failure (FFBF) and distant metastasis (FFDM). Outcomes were assessed using Kaplan\u2013Meier methods and Cox proportional hazards modeling. Results: At 5 years, high-risk patients demonstrated FFBF of 83% and FFDM of 89%, with significantly worse outcomes among very high-risk subgroups. Men with PSA &gt; 20 ng\/mL as their only high-risk feature (n = 49) achieved superior outcomes compared with other high-risk patients (5-year FFBF 94% vs. 74%; FFDM 97% vs. 82%; both p = 0.05), comparable to intermediate-risk disease. On multivariable analysis, Gleason score and clinical T-stage independently predicted poorer outcomes, whereas PSA &gt; 20 alone did not. Conclusions: PSA &gt; 20 ng\/mL as an isolated high-risk feature is associated with favorable outcomes following definitive RT and appears to be the weakest NCCN high-risk criterion. These findings support refined risk stratification and raise the possibility of treatment de-escalation in select patients.<\/jats:p>","DOI":"10.3390\/jcm15031119","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T17:38:34Z","timestamp":1769794714000},"page":"1119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High-Risk Prostate Cancer Treated with Radiation Therapy: Favorable Outcomes in Men with PSA &gt; 20 as the Sole High-Risk Factor"],"prefix":"10.3390","volume":"15","author":[{"given":"Aoi","family":"Shimomura","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abed R.","family":"Kawakibi","sequence":"additional","affiliation":[{"name":"Department of Radiation and Cellular Oncology, University of Chicago Medical Center, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muzamil","family":"Arshad","sequence":"additional","affiliation":[{"name":"Department of Radiation and Cellular Oncology, University of Chicago Medical Center, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4701-2469","authenticated-orcid":false,"given":"Stanley L.","family":"Liauw","sequence":"additional","affiliation":[{"name":"Department of Radiation and Cellular Oncology, University of Chicago Medical Center, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.urology.2012.07.040","article-title":"Contemporary evaluation of the National Comprehensive Cancer Network prostate cancer risk classification system","volume":"80","author":"Reese","year":"2012","journal-title":"Urology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1001\/jama.280.11.969","article-title":"Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer","volume":"280","author":"Whittington","year":"1998","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.eururo.2013.03.033","article-title":"A new risk classification system for therapeutic decision making with intermediate-risk prostate cancer patients undergoing dose-escalated external-beam radiation therapy","volume":"64","author":"Zumsteg","year":"2013","journal-title":"Eur. 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