Prostate Advances in Comparative Evidence

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).