SABR-Dual: a phase II/III trial of two-fraction versus five-fraction stereotactic radiotherapy for localized low- and favorable intermediate-risk prostate cancer

Abstract

Background Dose-escalated radiotherapy is known to improve progression free survival in patients with localized prostate cancer, and recent advances have led to the standardization of ultrahypofractionated stereotactic ablative radiotherapy (SABR) delivered in just 5-fractions. Based on the known effectiveness of the accepted though invasive 2-fraction treatment method of high-dose-rate brachytherapy and given the ubiquity of prostate cancer, a further reduction in the number of treatments of external-beam SABR is possible. This study aims to evaluate the safety, efficacy, and non-inferiority of generalizable 2-fraction SABR compared to the current 5-fraction regimen. Methods 502 patients will be enrolled on this phase II/III randomized control trial. Eligible patients will have previously untreated low- or favorable intermediate-risk adenocarcinoma of the prostate. Patients will be randomized between standard SABR of 40 Gy in 5 fractions given every-other-day and 27 Gy in 2 fractions at least two days apart but completing within seven days. MRI-based planning, radiopaque hydrogel spacer insertion, and fiducial marker placement are required, and SABR will be delivered on either a standard CT-guided linear accelerator or MR-LINAC. The primary endpoint will be freedom from disease progression, with additional secondary clinical, toxicity, and quality of life endpoints. Discussion This study will be the largest prospective randomized trial, adequately powered to demonstrate non-inferiority, comparing 2-fraction SABR to standard 5-fraction SABR for localized prostate cancer. As the protocol does not obligate use of an MRI-LINAC or other adaptive technologies, results will be broadly generalizable to the wider community. Trial registration This trial is registered on Clinicaltrials.gov: ClinicalTrials.gov Identifier: NCT06027892.

Stereotactic Body Radiotherapy (SBRT) to Localised Prostate Cancer in the Era of MRI-Guided Adaptive Radiotherapy: Doses Delivered in the HERMES Trial Comparing Two- and Five-Fraction Treatments

“…With 68% of men in MIRAGE and all men in HERMES receiving hormonal treatment the data on PSA kinetics from these small trials are still maturing. A secondary end point of HERMES includes 5-year biochemical recurrence-free survival, which will help to confirm the safety of CTV-PTV margin reduction in the context of 2-fraction prostate MRIgART, along with other two fraction trials such as FORT (NCT04984343), iSMART (NCT05600400) and SABR-Dual (NCT0602789) [ 37 , 38 ]. Cost-effectiveness of 2-fraction vs. 5-fraction MRIgART, or longer schedules, is yet to be determined.…”

The role of a radiopaque peri-rectal hydrogel spacer in aiding accurate daily image-guidance for prostate stereotactic radiotherapy

“…There was no correlation between setup consistency and prostate volume, and accuracy of the novel methodology was seen in SABR targeting the prostate alone, SVs, and pelvic lymph nodes. Newer technologies have been reported to enhance intra-fraction accuracy using either live- or interval timed-tracking of fiducial markers ( 30 ), or of the prostate itself ( 31 ). These can be further methods for enhancing precision during delivery of radiation therapy, though some of these abilities are not widely available in many centers globally.…”