Prostate cancer (PCa) is the most common type of cancer to affect men and, unfortunately, for the majority of PCa patients, death is attributed to metastatic disease. Lifelong androgen deprivation therapy (ADT) with LHRH agonists can help delay cancer progression in metastatic PCa patients. However, patients eventually become castration-resistant (disease progression despite ADT) and develop progressive metastatic disease. This in turn impacts the patient's quality of life and survival. Recently, a new generation of hormonal therapy (such as Enzalutamide) has become available to these castration-resistant prostate cancer (CRPC) patients. We believe that the benefits from this new generation of hormonal therapy can be prolonged in CRPC patients who develop oligometastases by treating the metastatic lesions using stereotactic body radiotherapy (SBRT). This new radiation technique allows for the treatment of many different metastases throughout the body in a very precise manner. This metastases-directed therapy is a new treatment option for patients with a limited number of metastases (less than 5) at the time of recurrence.

This adaptive phase II/III randomized trial is designed to demonstrate that eradication of oligometastases by the new technique SBRT is a promising and emerging way to delay disease progression and to postpone second line systemic therapies. Only patients with an oligometastatic recurrence after local treatment with curative intent will be eligible to take part in this trial. All participating CRPC patients with oligometastases will receive either the standard of care (i.e. LHRH agonist in combination with the new generation of hormonal therapy \[Enzalutamide\]) or the experimental treatment (i.e. LHRH agonist in combination with the new generation of HT \[Enzalutamide\] plus the additional SBRT treatment). The patients will undergo different evaluations before treatment, such as imaging to confirm oligometastatic recurrence and blood tests. Patients will be stratified according to the location of metastasis (visceral \[with or without bone metastases\] vs. bone metastases alone) and PSA doubling time (≤ 3 vs. \> 3 months). As per the standard of care, patients will have PSA testing performed every 6-12 weeks and re-imaging at 6, 9, 12, 18 and 24 months or at PSA progression, whichever occurs first.

The primary objective of this study will be to evaluate the radiographic progression-free survival. We also want to determine the time to the start of second line systemic therapy, the prostate-cancer specific survival, the overall survival as well as to assess the quality of life, the toxicity and the PSA response. This study is the first randomized study in this setting and will employ a randomized phase II design to determine if a larger scale phase III trial is needed, thus the phase II/III design. The Phase II will consist of 130 CRPC patients with oligometastases, and the phase III will consist of the already randomized 130 patients plus an estimated 244 patients for a total sample size of 374 patients. This study will be conducted through the Genitourinary Radiation Oncology Group of Quebec (GROUQ) in different radiation oncology centres across Canada and the recruitment should be completed within 30 months of activation.