Partial Prostate Salvage High Dose Rate Brachytherapy

Study Overview
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Brief Summary
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A dose-response relationship for radiation in the management of prostate cancer is well established. Local recurrence of prostate cancer after external beam radiotherapy occurs in at least 40% of patients treated because of inability to deliver sufficient dose through external beam techniques. These patients respond well to re-irradiation using brachytherapy with about 50% of selected patients remaining free of recurrence 5 years after salvage. Advanced imaging using multiparametric Magnetic Resonance Imaging (mpMRI) allows identification of the site of recurrence, permitting partial prostate salvage brachytherapy. There is extensive literature on Low Dose Rate salvage brachytherapy but less on High Dose Rate.

Detailed Description
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Appropriately selected patients with histologically documented recurrence 3 years or more after initial external beam radiotherapy will undergo mpMRI for identification of the site of recurrence. A planning transrectal ultrasound (TRUS) will be obtained for fusion with the mpMRI and transposition of the target volume (GTV=gross tumor volume). A margin of 4.5 cm will be added to the GTV to create a focal planning target volume (PTV). The margin may be cropped at the interface with critical organs. Two fractions of HDR brachytherapy will be delivered, each from a single implant, 2 weeks apart. Following treatment patients will be monitored for toxicity and quality of life using the Expanded Prostate cancer Index (EPIC) questionnaire as well as the International Prostate Symptom score. Efficacy will be evaluated by monitoring the Prostate Specific Antigen (PSA) and repeat mpMRI at 2 years.

Official Title
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High Dose Rate Partial Prostate Brachytherapy as Salvage Treatment for Local Failures After Previous External Beam Radiotherapy

Conditions
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Recurrent Prostate Cancer

Intervention / Treatment
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* Radiation: HDR partial prostate brachytherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >45 and Life expectancy >10 years Previous External Beam Radiotherapy (EBRT) dose up to 78Gray/39 fractions, 81 Gray/45 fractions or 70 Gray/28 fractions > 3 year interval since EBRT No late toxicity from prior EBRT > grade 2 Rising PSA post EBRT > nadir + 2 ng/ml but < 10 ng/ml PSA Doubling time > 6 months Negative staging with CT scan of the abdomen/pelvis and bone scan Able to undergo multiparametric MRI with endorectal coil Radiographic evidence of dominant intraprostatic lesion (DIL) as only area of recurrence (i.e unifocal recurrence) and corresponding to site of original disease Biopsy confirmation of DIL with pathology review by British Columbia Cancer Agency GenitoUrinary pathologist (TB) Willing to provide informed consent History and physical examination within 90 days of registration ECOG performance status 0-1 prior to registration IPSS < 16, or adequate voiding study (post void residual < 100cc and peak flow rate > 10 cc/second). No prior trans urethral prostatic resection Recurrence suitable for implant with HDR brachytherapy as assessed on ultrasound simulation (maximum PTV ideally < 65% of prostate volume) No history of inflammatory bowel disease or previous rectal surgery Suitable for procedure under anesthesia, spinal or general INR <2.5 and platelet count >75 x 109/L Androgen Deprivation Therapy may be initiated at the discretion of the treating oncologist Exclusion Criteria: Not compliant with criteria above Unable to give informed consent

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Interventional Model Description: High Dose Rate brachytherapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HDR partial prostate brachytherapy<br>2 fractions of high dose rate prostate brachytherapy will be delivered to the site of recurrent disease as determined by mp-MRI | Radiation: HDR partial prostate brachytherapy<br>* temporary radioactive implant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late adverse gastrointestinal or genitourinary events grade 3 or higher | Common Terminology Criteria for Adverse Events (CTCAE V4.0) | 3-60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late Quality of Life | Expanded Prostate Cancer Index (EPIC) | 3-60 months | 
| Late lower urinary tract symptoms | International Prostate Symptom Score | 3-60 months | 
| Acute grade 3 or higher gastrointestinal or genitourinary adverse events | Common Terminology Criteria for Adverse Events (CTCAE V4.0) | 0-3 months | 
| Acute Quality of Life changes | Expanded Prostate Cancer Index (EPIC) | 0-3 months | 
| Acute lower urinary symptoms | International Prostate Symptoms Score | 0-3 months | 
| Biochemical disease free survival | PSA < 0.4 ng/ml at 60 months | 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent prostate cancer, mpMRI, salvage HDR brachytherapy