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

## TL;DR

Men with high-risk prostate cancer due only to high PSA levels had better outcomes with radiation therapy compared to other high-risk groups.

## Contribution

Identifies PSA > 20 ng/mL as a weaker high-risk criterion for prostate cancer when used alone.

## Key findings

- Men with PSA > 20 ng/mL as sole high-risk factor had 94% 5-year freedom from biochemical failure.
- PSA > 20 alone did not independently predict poor outcomes in multivariable analysis.
- Outcomes for PSA-only high-risk group were comparable to intermediate-risk prostate cancer patients.

## 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.