prostate advances in comparative evidence

Conditions: Prostate Cancer

Summary: 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.


Eligibility 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).

Keywords: prostate cancer prostate adenocarcinoma organ-confined prostate cancer low-risk prostate cancer intermediate-risk prostate cancer