Prostate Advances in Comparative Evidence

Study Overview
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Brief Summary
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This study is an international multicentre randomised study of organ confined low and intermediate risk prostate cancer and is composed of two parallel randomisation schemes based on applicability of surgery as a treatment for the patient. Patients for whom surgery is a consideration are randomised to either laparoscopic prostatectomy or prostate SBRT. Patients for whom surgery is not a consideration are randomised to either conventionally fractionated radiation therapy or prostate SBRT. Efficacy, toxicity and quality of life outcomes will be compared across the pairs in each randomisation.

Official Title
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International Randomised Study of Laparoscopic Prostatectomy vs Stereotactic Body Radiotherapy (SBRT) and Conventionally Fractionated Radiotherapy vs SBRT for Early Stage Organ-Confined Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Procedure: Laproscopic Prostatectomy
* Radiation: Conventionally Fractionated Prostate Radiotherapy
* Radiation: Prostate SBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All of the following criteria are mandatory for inclusion: Histological confirmation of prostate adenocarcinoma with a minimum of 10 biopsy cores taken within 18 months of randomisation. Gleason score ≤ 3+4 Men aged ≥18 Clinical and MRI stage T1c -T2c, N0-X, M0-X (TNM 6th Edition [72], See Appendix 1) PSA ≤ 20 ng/ml Pre-enrollment PSA must be completed within 60 days of randomisation Patients belonging in one of the following risk groups according to the National Comprehensive Cancer Network (www.nccn.org): Low risk: Clinical stage T1-T2a and Gleason ≤ 6 and PSA < 10 ng/ml, or Intermediate risk includes any one of the following: Clinical stage T2b orT2c PSA 10-20 ng/ml or Gleason 3+4 WHO performance status 0 - 2 Prostate volume ≤ 90 cc measured within 6 months of randomisation (height*width*length *π/6) Ability of the research subject to understand and the willingness to sign a written informed consent document Exclusion criteria: One of the following criteria is sufficient for exclusion: Clinical stage T3 or greater Gleason score ≥ 4 + 3 High risk disease defined by National Comprehensive Cancer Network (www.nccn.org) 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 LHRH agonists and antagonists and anti-androgens) Any prior active treatment for prostate cancer. 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 artifacts Medical conditions likely to make radiotherapy inadvisable eg inflammatory bowel disease, significant urinary symptoms Anticoagulation with warfarin/ bleeding tendency making fiducial placement or surgery unsafe in the opinion of the clinician (see section 11, Treatment). Participation in another concurrent treatment protocol for prostate cancer

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Laparoscopic Prostatectomy vs prostate SBRT<br>Patients for whom surgery is considered will be randomised to laparoscopic prostatectomy or prostate SBRT delivered with 36.25 Gy in 5 fractions. | Procedure: Laproscopic Prostatectomy<br> <br> Radiation: Prostate SBRT<br>* Prostate SBRT delivered to a dose of 36.25 Gy in 5 fractions.<br>|
| Active Comparator: Conventionally Fractionated RT vs Prostate SBRT<br>Patients for whom surgery is not considered or who refuse surgery will be randomised to either conventionally fractionated radiotherapy delivered to a dose of 78 Gy in 2 Gy fractions or SBRT delivered with 36.25 Gy in 5 fractions. | Radiation: Conventionally Fractionated Prostate Radiotherapy<br>* Conventional fractionation delivered to a dose of 78 Gy in 2 Gy fractions.<br>Radiation: Prostate SBRT<br>* Prostate SBRT delivered to a dose of 36.25 Gy in 5 fractions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical progression-free survival | Biochemical progression is defined as follows: For conventional radiation and SBRT arms- Phoenix definition; For surgical arm- PSA > 0.2 ng/mL. | 5 years (primary timepoint) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity assessment for surgical and SBRT arm | CTCAEv4.03 and RTOG for acute and late toxicity. Clavien scale used to assess acute post surgical complications for surgical patients only. | 10 years | 
| Toxicity assessment for conventionally fractionated and SBRT arm | CTCAEv4.03 and RTOG acute and late toxicity scoring. During the treatment period of conventional radiation therapy and SBRT, treatment associated toxicities are assessed using RTOG scoring only. | 10 years | 
| Patient reported outcomes and quality of life assessment for all treatment arms | International Index of Erectile Function-5 (IIEF-5), International Prostate Symptom Score (IPSS), Vaizey score (UK and US patients only) Expanded Prostate Index Composite-26 (EPIC-26) and PR-25 (PR-25 is optional) | 10 years | 
| Disease-specific and overall survival | Disease-specific and overall survival | 10 years | 
| Progression-free survival | Radiographic, clinical or biochemical evidence of local or distant failure | 10 years | 
| Commencement of androgen deprivation therapy | LHRH analogues, anti-androgens, orchidectomy | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate cancer, Prostate adenocarcinoma, Early stage prostate cancer, Organ-confined prostate cancer, Low-risk prostate cancer, Intermediate-risk prostate cancer