Prostate Cancer
Conditions
Keywords
Prostate cancer, Prostate adenocarcinoma, Organ-confined prostate cancer, Low-risk prostate cancer, Intermediate-risk prostate cancer
Brief 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.
Interventions
PROCEDUREProstatectomy
Radical prostatectomy: performed open, laparoscopically or using a robotically assisted laparoscopic approach.
RADIATIONConventionally Fractionated Prostate Radiotherapy
Conventional fractionation delivered to a dose of: (PACE-B) 78 Gy in 39 fractions or 62 Gy in 20 fractions; (PACE-C) 60 Gy in 20 fractions
RADIATIONProstate SBRT
Prostate SBRT delivered to a dose of 36.25 Gy in 5 fractions.
Sponsors
The Institute of Cancer Research, Sutton, Surrey, UK
Royal Marsden NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multicentre, international phase 3 randomised controlled study comprising three parallel randomisations with a common experimental arm.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PACE-B and PACE-C: Freedom from biochemical or clinical failure | 5 years from randomisation (primary timepoint) | Biochemical progression is defined as: Phoenix definition Clinical progression is defined as: commencement (PACE-B) or re-commencement (PACE-C) of androgen deprivation therapy, local recurrence, nodal recurrence and distant metastases |
| PACE-A: Co-primary patient reported outcomes of urinary incontinence and bowel bother | 2 years from treatment (primary timepoint) | Urinary incontinence assessed by the number of absorbent pads required per day to control leakage measured by The Expanded Prostate Cancer Index (EPIC) questionnaire. Bowel bother assessed by summary score from the EPIC questionnaire. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All arms: Patient reported acute and late bowel, bladder and erectile dysfunction symptoms. | 10 years | Assessed using International Index of Erectile Function-5 (IIEF-5), International Prostate Symptom Score (IPSS), Vaizey score, and Expanded Prostate Index Composite-26 (EPIC-26) instruments. |
| All arms: Disease-specific and overall survival | 10 years | Disease-specific and overall survival |
| All arms: Clinician reported acute toxicity | 10 years | CTCAE and RTOG (SBRT and conventional RT patients) or Clavien scale (surgical patients). |
| PACE-A and PACE-B: Commencement of androgen deprivation therapy; PACE-C: Re-commencement of androgen deprivation therapy | 10 years | LHRH analogues, anti-androgens, orchidectomy |
| PACE-A: Freedom from biochemical or clinical failure | 5 years from randomisation (primary timepoint) | Biochemical progression is defined as: Phoenix definition (SBRT arm) or \>0.2ng/ml (surgical arm) Clinical progression is defined as: commencement of androgen deprivation therapy, local recurrence, nodal recurrence and distant metastases |
| All arms: Progression-free survival | 10 years | Radiographic, clinical or biochemical evidence of local or distant failure |
| All arms: Clinician reported late toxicity | 10 years | CTCAE and RTOG (SBRT and conventional RT patients only). |
Countries
Canada, Ireland, New Zealand, United Kingdom
Outcome results
None listed