Evaluation of the Interest of Hyaluronic Acid in the Preservation of Sexual Function During Prostate Curietherapies

Study Overview
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Brief Summary
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Prostate cancer is the most common cancer in humans, but low mortality, around 10 / 100,000 patients / year. It differs from other cancers by its high rate of cure, as well as a long term survival. Numerous treatment techniques are available and of comparable effectiveness: as a result it must be given importance to the short and long term side effects of these different treatments. Prostate brachytherapy with permanent implants is thus one of the standard techniques for the treatment of localized prostate cancers of favorable grades (WHO grade 1-2). In comparison with prostatectomy and RTE, brachytherapy allows low rates of long-term urinary toxicities, and comparable rates of erectile function preservation. With regard to erectile dysfunction, their pathophysiology after irradiation is complex and poorly understood, including damage to the erector apparatus, innervation, vascularization, and of course the level of libido. As an example, the radiotherapy team of the Lyon Sud hospital showed that the delivering a the lowest dose of radiation to the pudendal arteries and to the penile bulb during RTE, leads to erectile preservation rates comparable with those from the literature with nearly 85% of patients with erectile function retained at 2 years . They were also able to retrospectively show that a lower dose to the pudendal arteries correlated with better erectile function during brachytherapy. The brachytherapy procedure requires general anesthesia and endorectal ultrasound, which are optimal conditions for injecting hyaluronic acid between the prostate, rectum, and pudendal arteries. This gesture has shown to induce very few morbidity. They want to demonstrate that the injection of hyaluronic acid during prostate brachytherapy will reduce the radiation dose to the pudendal arteries and penile bulb, and thus improve the rate of preservation of erectile function in selected patients. This randomized phase III study comparing dyserection rates after CT performed with (Arm A) and without (Arm B) injection of HA, in a patient population without erectile dysfunction before treatment.

Detailed Description
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Prostate cancer is the most common cancer in humans with an incidence of about 100 / 100,000 cases / year in Europe, but low mortality, around 10 / 100,000 patients / year. It differs from other cancers by its high rate of cure, as well as a long term survival. Numerous treatment techniques are available and of comparable effectiveness: as a result it must be given importance to the short and long term side effects of these different treatments. Prostate brachytherapy with permanent implants is thus one of the standard techniques for the treatment of localized prostate cancers of favorable grades (WHO grade 1-2). The overall survival and survival rates without biochemical recurrence at 5 and 10 years are comparable to those of other techniques such as prostatectomy or external radiotherapy (RTE), exceeding 95%. In comparison with prostatectomy and RTE, brachytherapy allows low rates of long-term urinary toxicities, and comparable rates of erectile function preservation. With regard to erectile dysfunction, their pathophysiology after irradiation is complex and poorly understood, including damage to the erector apparatus, innervation, vascularization, and of course the level of libido. As an example, the radiotherapy team of the Lyon Sud hospital showed that the delivering a the lowest dose of radiation to the pudendal arteries and to the penile bulb during RTE, leads to erectile preservation rates comparable with those from the literature with nearly 85% of patients with erectile function retained at 2 years (18.5% moderate erectile dysfunction at 2 years, for moderate to severe degradation rates usually seen between 30 and 70% after external beam radiotherapy. They were also able to retrospectively show that a lower dose to the pudendal arteries correlated with better erectile function during brachytherapy. The brachytherapy procedure requires general anesthesia and endorectal ultrasound, which are optimal conditions for injecting hyaluronic acid between the prostate, rectum, and pudendal arteries. This gesture has shown to induce very few morbidity. They want to demonstrate that the injection of hyaluronic acid during prostate brachytherapy will reduce the radiation dose to the pudendal arteries and penile bulb, and thus improve the rate of preservation of erectile function in selected patients. This randomized phase III study comparing dyserection rates after CT performed with (Arm A) and without (Arm B) injection of HA, in a patient population without erectile dysfunction before treatment.

Official Title
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Phase III Trial Randomized to Evaluate the Interest of Hyaluronic Acid in the Preservation of Sexual Function During Prostate Curietherapies

Conditions
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Prostate Cancer

Intervention / Treatment
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* Device: Hyaluronic acid arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18 to 80 years old. Patients over 75 years old must have a G8 score ≥ 14 or oncogeriatric assessment.The geriatrician's expertise will validate the brachytherapy treatment. Karnofsky performance status ≥ 60% (ECOG performance status 0-2) Patients diagnosed with histologically proven localized prostate adenocarcinoma Prostate cancer eligible for brachytherapy according to the following criteria: at. Low risk prostate cancer: Gleason score <7 and PSA <10 ng / ml AND cT1-cT2a Intermediate risk prostate cancers with a single adverse factor: Gleason score = 7 (3 + 4) OR PSA 10-15ng / ml OR cT2b-cT2c / ml less than 50% positive biopsies Volume of the prostate <60 cc No middle lobe IPSS <15/35 Initial IIEF5 score, no treatment, greater than or equal to 20/25 Patient able to sign an informed consent form Patient benefiting from a social insurance system or similar system Exclusion Criteria: Nodal or distant metastatic evolution History of abdominal or pelvic irradiation Anterior treatment for prostate cancer, including hormone therapy with LHRH analogue or GnRH antagonist. History of prostate resection, not allowing brachytherapy seeds implantation. Uncontrolled cancer (except basal cell skin cancer) Current clinical study that may interfere with this study Patient unable to complete a self-administered questionnaire and understand the ins and outs of the trial Major patients protected by law Allergy to hyaluronic acid

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hyaluronic acid arm<br>Patients included in this arm, will have, before insertion of brachytherapy seeds in the prostate, an injection of hyaluronic acid between the prostate, rectum, and pudendal arteries | Device: Hyaluronic acid arm<br>* Patients included in this arm, will have, before insertion of brachytherapy seeds in the prostate, an injection of hyaluronic acid between the prostate, rectum, and pudendal arteries<br>|
| Active Comparator: Conventional brachytherapy<br>Patients included in this arm will have the conventional brachytherapy. | Device: Hyaluronic acid arm<br>* Patients included in this arm, will have, before insertion of brachytherapy seeds in the prostate, an injection of hyaluronic acid between the prostate, rectum, and pudendal arteries<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| interest of Hyalurocnic injection to protect pudendal arteries during prostate brachytherapy in the preservation of Erectile function at 2years. | The primary endpoints is the comparison between the 2 groups of the proportion of patient with preserved erectile function. The erectile function will be assessed with the variation of IIEF-5 score between pre-treatment evaluation and 2years after treatment evaluation. Erectile function will be considered preserved in the absence of a decrease in the IIEF-5 score by more than 5 points. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of erectile function. | comparison between the 2 groups of the International Index of Erectile Function (IIEF5) score evolution during the 2 years of follow-up. | 2 years | 
| The IPDE5 consumption at 2 years | The consumption of IPDE5 at 2 years will be defined by the proportion of patients who have used IPDE5 at least once after the intervention. | 2 years | 
| Erection satisfaction at 2 years | Erection satisfaction at 2 years will be measured using a numerical scale rated from 0 to 10, 0 being not at all satisfied and 10 completely satisfied | 2 years |