ABSTRACT
Purpose: Curative therapy for high-risk prostate cancer (HR-PrCa) includes androgen deprivation therapy (ADT) and a long course of pelvic and prostate boost radiotherapy (RT), which adds a significant burden on patients. Several non-randomized studies in the past 10 years suggested that 3-fraction Stereotactic body radiotherapy (SBRT) regimens provide promising rates of disease control and may be able to replace the conventionally fractionated (CF) External Beam RT (EBRT) boost, improving significantly the convenience of RT treatment. To address the deficit in randomized data, we opened a regional Prostate Boost irradiation with SBRT (PBS) randomized controlled trial at Juravinski and Walker Family Cancer Centres, in 2019. Materials and Methods: Men with localized HR-PrCa receive ADT for a total duration of three years, pelvic CF-EBRT (45-46Gy in 23-25 fractions) and are randomized to either CF-EBRT boost (32-33Gy in 15-16 fractions) or SBRT boost (19.5-21Gy in 3 fractions) to prostate and seminal vesicles. All patients receive fiducial (gold seed) implants and planning margins compatible with SBRT, regardless of treatment arm. SBRT boost is delivered with a Cyberknife unit at the Juravinski Cancer Centre or with LINACbased VoluMetric Arc Therapy (VMAT) at the Walker Family Cancer Centre) and, therefore, cases are stratified per treatment centre. Primary endpoint is quality of life (based on EPIC), and secondary endpoints include treatment-related toxicity and biochemical control. Biospecimens are collected for future analysis. Salient methodological differences between our study and a 2-fraction randomized phase II trial reported very recently (HYPO-PROST, Nov.2020) include fiducial-guided SBRT-based boost treatment and higher dose weekly fractions of boost RT. Results: We have completed nearly 50% of our target accrual of 100 patients. The mean age at enrollment was 73 (IQR 71-78) with a mean PSA of 12.7, IPSS score of 8.4 (IQR 4-13). 62.5% of the accrued patients had Gleason scores of 8 or higher, 23% had a PSA of 20 or higher, and 10% had findings consistent with cT3a or higher on DRE. Interim safety analysis of this trial will be completed in August 2021 and presented. To date, no Grade 3 or higher toxicity has been reported in either treatment arm. No biochemical failure has been noted. Conclusions: Despite interruption due to the COVID-19 pandemic, accrual on this study is progressing well with no unexpected toxicity or treatment failures detected. This study provides a formal evaluation of SBRT as a boost RT technique in HR-PrCa in a randomized setting. It is an important endeavour given the potential to develop a safe and convenient treatment for HR-PrCa.