# Influence of PSA level at salvage radiotherapy on metastasis-free survival following radical prostatectomy

## TL;DR

Lower PSA levels before salvage radiotherapy after prostatectomy are linked to better cancer outcomes, especially in high-risk patients.

## Contribution

This study provides evidence supporting early salvage radiotherapy initiation at PSA < 0.5 ng/ml for improved metastasis-free survival.

## Key findings

- Early sRT at PSA < 0.5 ng/ml was associated with significantly better metastasis-free survival (HR: 8.44).
- High-risk patients with early sRT had even greater survival benefits (HR: 12.69).
- Multivariable analysis confirmed the independent benefit of early sRT for all and high-risk subgroups.

## Abstract

The optimal time point of salvage radiotherapy (sRT) for biochemical recurrence (BCR) following radical prostatectomy is still under debate. Current European guidelines recommend salvage intensity-modulated and image‐guided radiotherapy for men with two consecutive PSA rises. However, no specific PSA threshold for initiation time is recommended. Nonetheless, lower PSA level may be associated with better cancer-control outcomes.

Relying on the University Cancer Center Frankfurt database, we evaluated differences in metastasis-free survival (MFS) among patients treated with early sRT (< 0.5 ng/ml) vs. sRT at PSA ≥ 0.5ng/ml. Subgroup analyses addressed sRT patients with high-risk features for indication of adjuvant radiation therapy, including Gleason score 8–10 and/or pT3–4 stage and/or pN1.

Of 190 sRT patients, 69% received early sRT at median PSA 0.24ng/ml vs. 0.89ng/ml. MFS was significantly better for early sRT patients, relative to sRT at PSA > 0.5 ng/ml (hazard ratio [HR]: 8.44, p < 0.01). Similarly, sRT patients with high-risk features also had significant better MFS at sRT with PSA < 0.5ng/ml (HR: 12.69, p < 0.01). After additional multivariable adjustment, early sRT at PSA < 0.5ng/ml was independently associated with better MFS outcomes for all patients (HR: 8.2) and high-risk sRT subgroups (HR: 55.6, both p < 0.05). Finally, we validated the initiation of sRT at an even lower cut-off of a PSA level ≤ 0.25ng/ml. However, this did not result in a significantly different outcomes, probably due to sample size limitations.

Our results validate European guidelines’ recommendation to initiate sRT at low PSA levels < 0.5ng/ml providing better MFS, especially in patients with high-risk features, refusing adjuvant radiation therapy.

The online version contains supplementary material available at 10.1007/s00345-025-05840-w.