This is a study that assesses the safety and efficacy of using stereotactic radiotherapy in conjunction with hormone therapy for patients with metastatic prostate cancer where there are a limited number of metastatic tumours.

Patients will receive androgen deprivation therapy (ADT) for a minimum of 1 year. After this, an intermittent hormone therapy approach will be taken, where ADT will not be restarted until the prostate specific antigen (PSA) reaches a minimum of 10-15 ng/mL. Lupron 30 mg IM will be delivered every 4 months when on ADT.

The prostate (if not previously treated) will be treated to a dose of 35-40 Gy in 5 fractions. All visible nodal metastases will be treated to a dose of 30-35 Gy in 5 fractions. It is very likely that nodal metastases will shrink significantly (often completely) with ADT. In this scenario, the involved nodal regions will be treated to a more modest dose of 25 Gy in 5 fractions (roughly equivalent to a dose of 46 Gy in 23 fractions assuming an α/β value of 1.4). Non-spine bone metastases will be treated to a dose of 30-40 Gy in 5 fractions. Metastases in the brain, spine, lung, liver, and adrenal will be treated according to established stereotactic radiotherapy (SRT) policies at Sunnybrook Odette Cancer Centre. Comprehensive SRT should be delivered within 3 months of starting ADT.

During any "off" period of ADT (before the PSA rises above 10-15 ng/mL), comprehensive SRT can be repeated if there are new oligometastases that become visible. One month after initiation comprehensive SRT, patients will be contacted to assess for acute toxicities.

After completion of radiotherapy to all disease sites, patients will be followed every 3-4 months with PSA testing until the development of castrate resistant prostate cancer. At the same time points, late toxicity and quality of life will be collected for a minimum of 2 years. Computed tomography (CT) of the chest/abdo/pelvis +/- magnetic resonance imaging (MRI) of previously irradiated body sites and bone scan will be performed whenever the PSA reaches ≥ 10 ng/mL (prior to re-starting androgen deprivation therapy during intermittent hormone therapy approach), or at a minimum frequency of once per year.

Inclusion Criteria:

• Able to provide informed consent.
• ECOG performance status 0-1.
• Histologic confirmation of prostate adenocarcinoma.
• Stage IV disease, with up to 5 metastatic tumours outside of the prostate and pelvic lymph nodes.
• ≤ 3 tumours within any given organ system (e.g. up to 3 brain metastases, or 3 liver metastases).
• All sites of disease are amenable to stereotactic radiotherapy.

Exclusion Criteria:

• Castrate resistant prostate cancer.
• Evidence of spinal cord compression.
• Previous radiotherapy for current cancer (with the exception of upfront management of the primary prostate tumour, brain metastasis(es) prior to androgen deprivation therapy).
• Inability to safely treat all sites of visible disease.
• Prior malignancy within the past 5 years, excluding non-melanoma skin cancer, and in-situ cancer.