# Reirradiation of Local Recurrences of Prostate Cancer: PROSTARE (PROstate Cancer STereotActic REirradiation) Early Safety Analysis of a Phase 2 Study with a Limited Cohort

## TL;DR

This study shows that re-irradiating prostate cancer recurrences with a focused radiation technique is safe and effective, with minimal severe side effects and significant PSA level reductions.

## Contribution

The study introduces focal salvage stereotactic body radiotherapy as a low-toxicity treatment option for prostate cancer recurrence after prior radiation.

## Key findings

- Only 4.8% of patients experienced Grade 3 toxicity, with no severe complications like fistulas or necrosis.
- All patients showed a PSA decline, with 71.4% achieving more than 50% reduction.
- Larger treatment volumes (PTV > 13 cc) may marginally increase side effects.

## Abstract

The PROSTARE study is an ongoing prospective clinical trial investigating the safety of focal salvage stereotactic body radiotherapy (s-SBRT) for patients with local prostate cancer recurrence after previous radiation therapy. This preliminary analysis reports on the first 21 evaluable patients out of a planned total cohort of 55. The results so far show that the treatment is safe and effective; severe side effects (Grade 3) were rare, occurring in only one patient (4.8%), with no cases of severe complications like fistulas or necrosis. Interestingly, an exploratory analysis suggests that a larger treatment volume (PTV > 13 cc) might be a marginal predictor of increased side effects. Regarding efficacy, all patients (100%) experienced a decrease in PSA levels, with 71.4% achieving a reduction of more than 50%. These early results support the use of focal s-SBRT as a promising, low-toxicity treatment option, though longer follow-up is needed to confirm these findings.

Objective: This study aims to report the early safety outcomes from an ongoing single-center, non-randomized phase 2 trial on focal salvage stereotactic radiotherapy (s-SBRT) for local prostate cancer recurrence. Materials and methods: This prospective phase 2 study includes patients with local recurrence after conventional or hypofractionated radiotherapy, ultrahypofractionated radiotherapy, or post-prostatectomy radiotherapy. The present analysis includes an initial subset of 21 out of 55 planned patients. All patients undergo mpMRI and PSMA-PET; biopsy is not required if imaging results are unambiguous. Focal s-SBRT is delivered to the recurrent lesion with a dose of 5 × 6.75 Gy. The primary endpoint is the rate of treatment-related CTCAE v5.0 grade ≥ 3 genitourinary (GU) or gastrointestinal (GI) toxicity. Secondary endpoints include early biochemical response (BR), defined as any PSA decline at 3 months. Results: With a median follow-up of 14 months (range: 4.5–25), one patient (4.8%) experienced both early and persistent late Grade 3 GU toxicity (bladder bleeding). Late Grade 2 GU and GI toxicities occurred in five (23.8%) and one (4.8%) patients, respectively. In exploratory univariable analysis, PTV volume 13 cc was identified as a marginal predictor for increased GU/GI radiation reactions (p < 0.1). Regarding efficacy, all 21 patients (100%) demonstrated an early biochemical response, with 15 patients (71.4%) achieving a PSA reduction of 50%. Conclusions: Focal s-SBRT demonstrates a favorable early safety profile and consistent biochemical response, supporting the preliminary safety of this ongoing study.