Prostate Advances in Comparative Evidence

This study is an international multicentre randomised study of low, intermediate, and high risk prostate cancer and is composed of three parallel randomisation schemes based on applicability of surgery as a treatment for the patient and risk group. Low and intermediate risk patients, for whom surgery is a consideration, are randomised to either prostatectomy or prostate SBRT. Low and intermediate risk patients, for whom surgery is not a consideration, are randomised to either conventionally fractionated radiotherapy or prostate SBRT. Intermediate and high risk patients, for whom ADT treatment is indiacted and surgery is not a consideration, are randomised to either conventionally fractionated radiotherapy or prostate SBRT. Efficacy, toxicity and quality of life outcomes will be compared across the pairs in each randomisation.

Inclusion critieria (all arms): * Histological confirmation of prostate adenocarcinoma within the last 18 months (unless on active surveillance and not clinically indicated) * Men aged ≥18 years at randomisation * WHO performance status 0 - 2 * Patients considered candidates for surgery are eligible for PACE-A; patients not considered candidates for surgery and patients who decline surgery or prefer to avoid surgery are eligible for PACE-B and PACE-C. * Ability of the research subject to understand and the willingness to sign a written informed consent document. Specific risk stratification inclusion criteria for PACE-A and PACE-B: * Minimum of 10 biopsy cores. * Gleason score ≤ 3+4 * Clinical and/or MRI stage T1c -T2c, N0-X, M0-X * PSA ≤ 20 ng/ml (completed within 60 days of randomisation) * Patients belonging to one of the following risk groups: * Low risk - patients with tumours meeting all of the following criteria: * Gleason ≤ 6 * Clinical stage T1-T2a * PSA \< 10 ng/ml (within 60 days prior to randomisation) * Intermediate risk - patients with tumours meeting any one of the following criteria: * Gleason 3+4 * Clinical stage T2b or T2c * PSA 10-20 ng/ml (within 60 days prior to randomisation) Specific risk stratification inclusion criteria for PACE-C: * Patient planned for a minimum of 6 months ADT (maximum of 12 months). Patients receiving extended androgen deprivation therapy (18 months maximum) to permit safe delay of radiotherapy as a result of the COVID19 pandemic (only) are eligible. * Gleason score ≤ 4+4 * MRI stage T1c -T3a, N0-X, M0-X * PSA ≤ 30 ng/ml (within 60 days prior to starting ADT) * Patients belonging to one of the following risk groups: * Intermediate risk - includes the presence of any of the following, assuming no high risk features apply: * Gleason 7 (3+4 or 4+3) * T2 (N0, M0-X) * PSA 10-20 ng/ml * High risk - patients with tumours that meet a maximum of 2 of the following criteria: * Gleason 4+4 (max ≤ 50% cores) * T3a (N0, M0) * PSA \>20 ng/ml Exclusion criteria (all arms): * Previous malignancy within the last 2 years (except basal cell carcinoma or squamous cell carcinoma of the skin), or if previous malignancy is expected to significantly compromise 5 year survival. * Prior pelvic radiotherapy. * Prior androgen deprivation therapy (including androgen agonists and antagonists) for PACE-A and PACE-B participants. * Any prior active treatment for prostate cancer (with the exception of ADT for PACE-C participants). Patients previously on active surveillance are eligible if they continue to meet all other eligibility criteria. * Life expectancy \<5 years. * Bilateral hip prostheses or any other implants/hardware that would introduce substantial CT artefacts. * Medical conditions likely to make radiotherapy inadvisable eg inflammatory bowel disease, significant urinary symptoms. * For patients having fiducials inserted: Anticoagulation with warfarin/ bleeding tendency making fiducial placement or surgery unsafe in the opinion of the clinician. * Participation in another concurrent treatment protocol for prostate cancer. Specific exclusion criteria for PACE-C: * \>14 weeks of androgen deprivation therapy prior to randomisation * Medical conditions likely to make ADT inadvisable (e.g. significant and ongoing cardiac issues).