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High-Risk Prostate Cancer Treated with Radiation Therapy: Favorable Outcomes in Men with PSA > 20 as the Sole High-Risk Factor

Year: 2026

Type: article

Abstract: Background/Objectives: The National Comprehensive Cancer Network (NCCN) classifies prostate cancer with PSA > 20 ng/mL as high risk; however, outcomes within this group are heterogeneous. Emerging data suggest that men with PSA > 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–Meier 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 > 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 > 20 alone did not. Conclusions: PSA > 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.

Source: Journal of Clinical Medicine

DOI: 10.3390/jcm15031119

Authors: Aoi Shimomura, Abed R. Kawakibi, Muzamil Arshad, Stanley L. Liauw

Institutions: Cedars-Sinai Medical Center, University of Chicago Medical Center

Language: English

Topic: Prostate Cancer Diagnosis and Treatment

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,137