Project 463259

External beam radiotherapy (EBRT), brachytherapy boost and androgen deprivation therapy (ADT) is the evidence-based standard of care for unfavourable risk (high-tier intermediate or high risk) prostate cancer. Stereotactic body radiotherapy (SBRT) is a non-invasive high precision radiation technique. Guidelines support SBRT in favourable risk but not for unfavourable risk disease due to the paucity of data at the time the guideline was formulated (2017-2018). To date over 136 unfavourable risk patients have been prospectively accrued to trials led by Sunnybrook Health Sciences Centre where 5 divided doses delivering a total of 25 Gy to the pelvis and 35 - 40 Gy to the prostate have been prescribed. There have been no cancer recurrences and no severe toxicities with follow-up out to 7 years. The oncologic outcomes and tolerability with the proposed intervention in this trial (SBRT, pelvic RT and ADT) appear similar to what is published for brachytherapy boost, pelvic RT and ADT. Other important advantages for the patient and the healthcare system favouring SBRT are the fewer treatment visits (5 for SBRT boost versus 24 for EBRT + brachytherapy boost), lower cost, avoidance of a general anaesthetic and not having to use scarce resources (brachytherapy suite and staff). We feel the best way to properly determine whether SBRT boost is non-inferior to brachytherapy boost for unfavourable risk patients is to conduct a large, phase 3, non-inferiority randomized controlled trial. If the proposed trial, ASCENDE-SBRT, shows that SBRT boost is non-inferior to brachytherapy boost for progression-free survival and is better tolerated, SBRT boost would likely become the preferred treatment choice in the future.