Prostate Advances in Comparative Evidence

Inclusion Criteria

• 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).