Botulinum Toxin Injection With Prostate Brachytherapy

Study Overview
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Brief Summary
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The purpose of this study is to see if botox injection into the prostate during seed implantation (brachytherapy) for prostate cancer a) improves urinary symptoms or avoids need for urinary tract instrumentation over the 6-8 month post-operative period when one wants to avoid manipulating the radioactive seeds, and b) speeds up the drop in PSA. Patients will be randomized to botox vs saline injection, at the completion of the seed implantation procedure.

Detailed Description
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Brachytherapy is a popular treatment modality for localized prostate cancer, where radioactive seeds are implanted through 18 gauge needles into the prostate via a perineal template with rectal ultrasound guidance. The radioactivity is delivered over several months, depending on the isotope used. During this time, there can be exacerbation of urinary voiding symptoms from early edema of the prostate gland due to the implantation procedure, then later from the inflammatory reaction of the radiation. Because the initial acute inflammation may persist for many months despite steadily declining doses of radiation, attempts are made to minimize urinary symptoms prior to brachytherapy with pharmacologic therapy (alpha-blockers) or minimally invasive surgical therapy (transurethral incision or limited transurethral resection to avoid significant distortion of the prostate parenchyma for future seed implantation). Even with these precautions, around 30-40% of brachytherapy patients will still develop voiding symptoms. With such bothersome symptoms, intervention is deferred for at least 8-10 months to avoid distorting the planned field of radiation. Once symptoms develop, various additional pharmacologic measures are employed, such as increased doses of alpha-blockers, medrol steroid taper, and non-steroidal anti-inflammatory agents. Some patients require intermittent self-catheterization or suprapubic catheter for urinary diversion. Botulinum toxin has been used for cosmetic uses, and has been successfully used for treatment of overactive bladder, external sphincter dyssynergia, and benign prostatic hyperplasia (BPH). The studies with BPH show reduction in symptoms scores, PSA, and prostate volume, the latter from atrophy due to the denervation effect. The response lasts for 6-9 months. We propose to study botox intraprostatic injection during brachytherapy to see whether this improves urinary symptoms or avoids need for urinary tract instrumentation over this 6-8 month post-operative period when one wants to avoid manipulating the radioactive seeds. We will also monitor PSA, and see if there is any measurable augmentation of PSA decline with botox + Brachytherapy vs Brachytherapy alone. We will randomize patients to botox (100 units for < 30 cc prostate; 200 units for > 30 cc prostate) vs saline injection, administering 2 transperineal injections into both lateral lobes of the prostate (25-50 mg per injection), just 5-10 mm proximal to the bladder neck. Study design: N= 60 (30 receive Botox, 30 receive saline) Followup: AUA Symptoms scores weekly for 4 weeks, monthly thereafter Medications for urinary symptoms Need for catheterization PSA checked at 1 mo, 3 mo, 6 mo, 9 mo, 1 year, 15 mo, 18 mo, 24 mo

Official Title
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Botulinum Toxin Injection With Prostate Brachytherapy: A Randomized, Placebo-controlled Study Monitoring Urinary Symptoms and PSA

Conditions
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Prostate Cancer, Lower Urinary Tract Symptoms, Radioactive Seed Implantation

Intervention / Treatment
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* Drug: Botox injection
* Drug: Saline injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven prostate cancer undergoing brachytherapy Exclusion Criteria: Prior allergic reaction to botulinum toxin

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Botox injection | Drug: Botox injection<br>* Intraprostatic injection of Botox (100 units for < 30 cc prostate; 200 units for > 30 cc prostate) administering 2 transperineal injections into both lateral lobes of the prostate (25-50 units per injection), just 5-10 mm proximal to the bladder neck.<br>* Other names: Botox;|
| Placebo Comparator: B<br>Saline injection | Drug: Saline injection<br>* Saline injection, administering 2 transperineal injections into both lateral lobes of the prostate (1-2 cc per injection), just 5-10 mm proximal to the bladder neck.<br>* Other names: NS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary symptoms |  | Weekly for 4 weeks, monthly thereafter until 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA |  | 1 mo, 3 mo, 6 mo, 9 mo, 1 year, 15 mo, 18 mo, 24 mo | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate specific antigen (PSA), Prostate cancer, Lower urinary tract symptoms, Radioactive seed implantation