Medical and Economic Evaluation for Intermediate-risk Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
The aim of the present phase III study is two-folded: 1) to show a superiority of external beam radiotherapy combined with a brachytherapy boost versus exclusive external beam radiotherapy and 2) to evaluate the economic impact of each treatment. The study includes 33 cancer centres, the inclusion time is of 2 years and the follow-up is of 5 years.

Official Title
-----------------
Medical and Economic Evaluation of an External Beam Radiotherapy Combined With a Brachytherapy Boost Compared With an Exclusive External Beam Radiotherapy for Intermediate-risk Prostate Cancer

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

Intervention / Treatment
-----------------
* Radiation: Brachytherapy boost with external beam radiotherapy
* Radiation: Exclusive external beam radiotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age between 18 and 80 years; life expectancy of greater than 10 years; prostate adenocarcinoma histologically proven; prostate cancer has to be of intermediate-risk based on at least one of the three following criteria: PSA between 10 ng/ml and 20 ng/ml, and/or a Gleason score of 7 and/or a T2B. Karnofsky performance status ≥ 60% and consequently performance status ECOG 0-2. the patient has to be the beneficiary of the social security system (order n° 2006-477 from April 26th 2006); the signed consent form. Exclusion Criteria: PSA level > 20; Gleason > 7; clinical T3A or T3B or MRI (a simple suspicion/ doubt on the MRI regarding the T3A won't be an exclusion criterion); prostate volume > 60 cc; pelvic lymph nodes involvement at dissection or imaging (ADP > 1.5 cm); concurrent hormone therapy; the presence of distant metastasis (M1); history of abdominal or pelvic irradiation; history of prostate resection in the previous 6 months and/or not allowing the implantation of markers; history of uncontrolled cancer and/or treated since less than 5 years (excepting the basal-cell carcinoma); urinary discomfort with an IPSS (International Prostate Symptom Score) > 15 (without alpha-blocking); inflammatory bowel disorder such as ulcerative colitis or the Crohn's disease; other undergoing study that may interfere with the present study; patient under legal protection measure.

Ages Eligible for Study
-----------------
Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brachytherapy boost<br>Brachytherapy boost with external beam radiotherapy. External beam radiotherapy of 46 Gy delivered to the prostate and the first centimeter of the seminal vesicles with a brachytherapy boost (of iodine-125 seeds (110Gy) or high dose rate (14Gy) with iridium-192) only to the prostate. Each center will choose the appropriate brachytherapy technique | Radiation: Brachytherapy boost with external beam radiotherapy<br>* Bras A: External beam radiotherapy of 46 Gy delivered with a linear accelerator (Varian) to the prostate and the first centimeter of the seminal vesicles with a brachytherapy boost (of iodine-125 seeds from Bard (110Gy) or high dose rate (14Gy) with a iridium-192 source) only to the prostate. Each center will choose the appropriate brachytherapy technique. The number of seeds or needles will depend on the prostate's volume.<br>|
| Active Comparator: Exclusive external beam irradiation<br>Exclusive external beam radiotherapy. External beam radiotherapy of 46 Gy delivered to the prostate and the first centimeter of the seminal vesicles with an external beam radiotherapy of 80 Gy to the prostate alone. | Radiation: Exclusive external beam radiotherapy<br>* Bras B: External beam radiotherapy of 46 Gy delivered with photons and a linear accelerator (Varian) to the prostate and the first centimeter of the seminal vesicles with an external beam radiotherapy of 80 Gy to the prostate alone.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the biochemical relapse free survival of the patients in two groups at 5 years for an external beam radiotherapy with a brachytherapy boost versus an exclusive external beam radiotherapy | Biochemical relapse is defined using the Phoenix definition of nadir of Prostate Specific Antigen + 2 ng/ml. This will be studied for both arms | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The evaluation of the overall survival at 5 years. | All cause mortality | 5 years | 
| The evaluation of the specific survival at 5 years | Mortality due to prostate cancer | 5 years | 
| The evaluation of the survival without any metastatic evolution at 5 years |  | 5 years | 
| The study of all toxicities | The toxicities include: acute and late toxicities, sexual toxicities, the quality of life of the patients (CTCAE version 4.0) | 5 years | 
| Medical and economical evaluation. | The complete medical and economical evaluation of the strategies | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prostate, external beam radiotherapy, brachytherapy boost, economical evaluation