Focal Prostate Ablation Versus Radical Prostatectomy

Study Overview
=================
Brief Summary
-----------------
This study aims to compare the treatment results of HIFU and Radical prostatectomy.

Detailed Description
-----------------
The FARP randomized control study will compare focal ablation of prostate using High Intensity Focused Ultrasound (HIFU) applied by FocalOne® or TULSA® device versus Radical Prostatectomy (RP) in patients with unilateral, intermediate risk prostate cancer.

Official Title
-----------------
A Randomized Control Trial of Focal Prostate Ablation Versus Radical Prostatectomy

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Device: Focal HIFU treatment using Focal One (EDAP TMS) or TULSA-PRO (Profound Medical)
* Procedure: Radical prostatectomy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: PSA ≤ 20 ng/ml Initial diagnosis of localized prostate cancer (stage ≤ T2b) Biopsy proven unilateral prostate cancer Gleason score 3+3 and not eligible to active surveillance program [cancer invades over a length of at least 5 mm and MRI demonstrates cancer suspicious lesion score ESUR ≥ 4/5 localized in line with the biopsy AND/OR Gleason score 3+4 (without length criteria of positive biopsies or tumor volume on MRI) Patients may have biopsy verified clinically insignificant prostate cancer on the contra-lateral prostate lobe (Gleason score 3+3, maximal cancer core length < 5 mm, MRI score ESUR ≤ 3) Exclusion Criteria: Clinical stage T3 Metastatic lymph node on MRI or CT Patients already treated for Pca (hormone therapy, EBRT) Patients with contra-indications to MRI Patients with inflammatory bowel disease or rectal fistula History of previous pelvic radiotherapy History of bladder cancer History of bladder neck or urethral stricture Urogenital infection in progress Allergy to latex or gadolinium Patients on life support or suffering form unstable neurological diseases

Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Focal prostate cancer treatment by HIFU<br>Patients with target lesion distance < 30 mm from the rectum will be treated with High Intensity Focused Ultrasound (HIFU) applied by FocalOne HIFU device and patients with lesion > 30 mm from the rectum will be treated with TULSA applied by TULSA-PRO. | Device: Focal HIFU treatment using Focal One (EDAP TMS) or TULSA-PRO (Profound Medical)<br>* HIFU arm: Focal ablation of prostate cancer using HIFU Focal One or TULSA -PRO<br>|
| Active Comparator: Radical Prostatectomy<br>Robot assisted laparoscopic radical prostatectomy or open retro-pubic radical prostatectomy will be performed using validated radical prostatectomy technique. Nerve sparing surgery on side of cancer free prostate lobe will be performed and type of nerve sparing procedure will be specified. | Procedure: Radical prostatectomy<br>* Prostatectomy arm: Robot assisted or open retropubic prostatectomy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment failure. | Treatment failure in HIFU focal ablation arm is classified as the need for secondary whole gland treatment as radical prostatectomy or EBRT. Treatment failure in radical prostatectomy arm is classified as PSA > 0.2 or positive surgical margins and need for EBRT. | At 36 months from the treatment date. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare urinary continence between focal ablation and radical prostatectomy. | Expanded Prostate Cancer Index Composite-26 (EPIC-26) questionnaire for the evaluation of continence will be used. Variation in urinary continence according to the number of pads used/day due to continence problems compared to baseline. Categories are defined as (full continence= 0 pads/day; security pad or mild incontinence =1pad/day; moderate incontinence= 2pads/day and severe incontinence >2pads/day). | Within 36 months from the treatment date. | 
| To compare erectile function between focal ablation and radical prostatectomy. | International Index of Erectile Function (IIEF-5) questionnaire for the evaluation erectile function will be used. A score of 1-5 is awarded to each of the 5 questions. Change in total score will be measured between the baseline and most recent follow-up visit. | Within 36 months from the treatment date. | 
| To compare quality of life between focal ablation and radical prostatectomy. | The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-c30) for the evaluation of quality of life between focal ablation and radical prostatectomy will be used. | Within 36 months from the treatment date. | 
| Focal ablation failure. | Focal ablation failure is classified as presence of clinically significant cancer on control MRI-3D TRUS image fusion guided biopsy in the treated prostate zone. At least 2 targeted biopsy cores will be localized in the treatment zone. Prostate biopsy will be performed at 12 and 36 months from the treatment date. | Within 36 months from the treatment date. | 
| To compare short, medium and long term adverse events related to treatments. | All adverse events will be registered prospectively. | Within 36 months from the treatment date | 
| Diagnostic failure. | Diagnostic failure is classified as diagnosis of clinically significant cancer localized outside of treatment zone in treated lobe and in any region of non- treated prostate lobe. MRI and systematic radom prostate biopsy form each prostate sextant will be performed and location of each biopsy trajectory will be registered using Trinity (Koelis) device. Prostate biopsy will be performed at 12 and 36 months from the treatment date. | Within 36 months from the treatment date. | 
| Cancer progression including development of metastases. | Whole body MRI or PET CT will be performed if suspicion on metastases. | Within 36 months years from the treatment date. | 
| Cancer specific and all-cause mortality. | Cause of the mortality will be evaluated and registered. | Within 36 months from the treatment date. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prostate Cancer, HIFU Focal Treatment, Radical prostatectomy