Phase III randomised controlled trial on PSMA PET/CT guided hypofractionated salvage prostate bed radiotherapy of biochemical failure after radical prostatectomy for prostate cancer (PERYTON-trial): study protocol

Abstract

Background Salvage external beam radiotherapy (sEBRT) for patients with a biochemical recurrence (BCR) after radical prostatectomy provides a 5-year biochemical progression-free survival up to 60%. Multiple studies have shown that dose escalation to the primary prostate tumour improves treatment outcome. However, data is lacking on the role of dose escalation in the recurrent salvage setting. The main objective of the PERYTON-trial is to investigate whether treatment outcome of sEBRT for patients with a BCR after prostatectomy can be improved by increasing the biological effective radiation dose using hypofractionation. Moreover, patients will be staged using the PSMA PET/CT scan, which is superior to conventional imaging modalities in detecting oligometastases. Methods The PERYTON-study is a prospective multicentre open phase III randomised controlled trial. We aim to include 538 participants (269 participants per treatment arm) with a BCR after prostatectomy, a PSA-value of < 1.0 ng/mL and a recent negative PSMA PET/CT scan. Participants will be randomised in a 1:1 ratio between the conventional fractionated treatment arm (35 × 2 Gy) and the experimental hypofractionated treatment arm (20 × 3 Gy). The primary endpoint is the 5-year progression-free survival after treatment. The secondary endpoints include toxicity, quality of life and disease specific survival. Discussion Firstly, the high rate of BCR after sEBRT may be due to the presence of oligometastases, for which local sEBRT is inappropriate. With the use of the PSMA PET/CT before sEBRT, patients with oligometastases will be excluded from intensive local treatment to avoid unnecessary toxicity. Secondly, the currently applied radiation dose for sEBRT may be too low to achieve adequate local control, which may offer opportunity to enhance treatment outcome of sEBRT by increasing the biologically effective radiotherapy dose to the prostate bed. Trial registration This study is registered at ClinicalTrials.gov (Identifier: NCT04642027). Registered on 24 November 2020 – Retrospectively registered. The study protocol was approved by the accredited Medical Ethical Committee (METc) of all participating hospitals (date METc review: 23-06-2020, METc registration number: 202000239). Written informed consent will be obtained from all participants.

Moderate hypofractionated radiotherapy to the prostate bed with or without pelvic lymph nodes: a prospective trial

“…Half of the patients in our series underwent PSMA PET before undergoing radiotherapy, in line with current recommendations. Moreover, our patients underwent PSMA PET with PSA values < 0.5 ng/mL, aligning with the guidelines from recent series [34].…”

A Risk Model for Patients with PSA-Only Recurrence (Biochemical Recurrence) Based on PSA and PSMA PET/CT: An Individual Patient Data Meta-Analysis

“…Ongoing trials aims to elucidate the outcome of treatment for patients with PSA-only recurrence restaged with PSMA PET/CT. The PERYTON trial includes patients with a PSA < 1.0 ng/mL and a negative restaging PSMA PET/CT [ 28 ]. The trial compares conventional SaRT with hypofractionated SaRT.…”

Pretest PSA and Restaging PSMA PET/CT Predict Survival in Biochemically Recurrent Prostate Cancer

“…Ongoing BCR trials study salvage treatment based on restaging PSMA PET/CTs. The Peryton trial evaluates patients with negative PSMA PET/CTs and compares hypo-fractionated and conventionally fractionated RT [ 25 ]. The ADOPT trial studies oligorecurrent patients and evaluates whether ADT adds to MDT [ 26 ].…”