High-Dose-Rate Brachytherapy

Two hundred and nineteen thousand new cases of prostate cancer have been projected in the Unites States for 2007, with external beam radiotherapy (EBRT) constituting the mainstay of local therapy for an increasing proportion of newly diagnosed patients. Despite improvements in the delivery and reduction in associated toxicity of external beam radiotherapy, local persistence or recurrence of disease remains prevalent in 25-51% of patients. Local disease after EBRT is a risk factor for subsequent metastatic progression and prostate cancer-specific mortality, and is a cause of morbidity including hematuria, obstructive uropathy, and chronic pain. Given its prevalence, and the lack of satisfactory local salvage treatments, fear of prostate cancer recurrence has been shown to impose a substantial burden of suffering in patients.

Stereotactic needle placement under MRI-guidance enables two critical steps in tumor-targeted brachytherapy: 1) directly guiding brachytherapy catheters to sites of tumor recurrence, and 2) permitting treatment planning and delivery to be based on 3D MRI images. MRI-based HDR brachytherapy will precisely identify the location of brachytherapy catheters relative to the target volumes and adjacent normal structures at risk of radiation injury, obviating the need for invasive saturation (24-100) mapping biopsies.

This study will build the evidence supporting the concept of MRI-guidance and tumor-targeted HDR brachytherapy in the management of prostate cancer. This trial will strive to demonstrate improvements in technical performance under MRI-guidance, while exploring a novel paradigm of patient-specific modulation of dose intensity based on regions of tumor burden.

Inclusion criteria

• Prior enrollment of UHN 05-0641-C or UHN 12-5015-C (Arm 1)
• Histological evidence of recurrent prostate adenocarcinoma (Arm 1)
• PSA doubling time > 6 months (Arm 1)
• Intermediate and High-risk localized prostate cancer (>T1 or PSA>10 or Gleason > 6) (Arm 2)
• Planned for EBRT + HDR boost (+/- hormone therapy) (Arm 2)
• ECOG 0 or 1
• Age > 18 years
• Informed consent: All patients must sign a document of informed consent indicating their understanding of the investigational nature and risks of the study before any protocol related studies are performed.

Exclusion criteria

• Radiological evidence of regional or distant metastases
• Contraindications to MRI (Patient weight as per MRI Technologist's discretion, Patients with pacemakers, cerebral aneurysm clips, shrapnel injury, or implantable electronic devices not compatible with MRI)
• Bleeding diathesis and anti-coagulative therapy that cannot be temporarily ceased during brachytherapy
• Previous prostate brachytherapy
• Active hormonal therapy at time of brachytherapy (Arm 1)
• Previous pelvic radiotherapy (Arm 2)
• Contraindications to endorectal coil, surgically absent rectum, severe hemorrhoids or colorectal surgery.
• Latex Allergy
• Contraindications to conscious sedation, local anesthesia, or spinal/epidural anesthesia.
• IPSS >18
• Large TURP defect
• TURP within the past 6 months
• Prostate gland size >80cc (Arm 2, whole gland HDR patients only)
• History of Ulcerative Colitis and SLE (except for patients where the clinician determines benefit outweighs the risk of radiation)
• Other medical conditions deemed by the PI to make patient ineligible for MRI-guided Prostate HDR brachytherapy.