Comparative Study of Radiotherapy Treatments to Treat High Risk Prostate Cancer Patients

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate diagnosed within 6 monthsprior to randomization, (if longer than 6 months, needs to be approved by the PI).

• Clinical stage including at least one of the following: T3 or T4, Gleason Score > 8,and/ or Prostate-specific antigen (PSA) > 20 (ng/ml or μg/L).

• Pelvic and para-aortic lymph nodes must be negative on CT scan or MRI of the abdomenand pelvis performed within 12 (recommended time limit, may exceed in certain cases)weeks prior to randomization. For patients who have started androgen suppressionprior to randomization, CT or MRI may be done after start of therapy, provided it isdone no more than 28 days following start of androgen suppression therapy (any lymphnode appearing > 1.5 cm on CT or MRI must be histologically negative by eitherneedle aspirate or lymph node dissection performed within 12 weeks prior torandomization).

• Investigations, including chest x-ray (CXR is recommended and not mandatory) CT scanand bone scan (with radiographs of suspicious areas) have been performed within 12weeks (recommended time limit) prior to randomization and are negative formetastases. For patients who have started androgen suppression prior torandomization, bone scan may be done up to and including 28 days after thecommencement of therapy.

• Patients will have had a PSA test done at the time of diagnosis. This PSA test couldbe repeated within 28 days prior to randomization. The PSA value used to confirmhigh risk disease and the value to be entered on the eligibility checklist must bethe higher of these two values. These criteria will be the same regardless ofwhether or not the patient has initiated hormone therapy prior to randomization.

• The patient may have received prior androgen suppression therapy provided thatandrogen suppression therapy commenced no more than 28 days prior to randomization.

• The patient must not have received any cytotoxic anticancer therapy for prostatecancer prior to randomization. Patients may have received treatment with a 5-alpha-reductase inhibitor (e.g. Finasteride) for benign prostatic hypertrophy (BPH), which must have been discontinued prior to the randomization.

• ECOG performance status must be 0 or 1.

• Hematology and Biochemistry: Laboratory requirements have been done within 28-42days prior to randomization: hemoglobin > 100 g/L, absolute Neutrophils > 1.5 x 109/L, platelets > 100 x 109/L, serum creatinine < 1.5 x ULN

Exclusion Criteria:

• Patients with a history of other malignancies, except: non-melanoma skin cancer; orother solid tumours curatively treated with no evidence of disease for > 5 years.

• The presence of small-cell or transitional-cell carcinoma in the biopsy specimen.

• Patients who had previous chemotherapy for carcinoma of the prostate.

• Patients who had prior surgical treatment for carcinoma of the prostate apart fromtrans-urethral resection, including bilateral orchiectomy.

• Patients with any contraindication to pelvic radiotherapy: including, but notlimited to, previous pelvic radiotherapy. Inflammatory bowel disease (at thediscretion of the treating oncologist) or severe bladder irritability.

• Patients with serious non malignant disease resulting in a life expectancy less than 3 years.

• Other serious illness, psychiatric or medical condition that would not permit thepatient to be managed according to the protocol including active uncontrolledinfection and significant cardiac dysfunction. Patients with medical conditions thatwould contraindicate the treatment regimen outlined in the protocol [e.g. intake ofstudy drugs].

• Known hypersensitivity to any protocol-indicated study medications.

• Presence of bilateral hip replacement prostheses.

• Patients with history of severe congestive heart failure will not be eligible.

• Patients with congenital long QT syndrome or patients taking Class IA, Class III orClass IC anti-arrhythmic medications will require a cardiologist's evaluation priorto eligibility assessment. Patients with cardiovascular diseases can be included aslong as the benefits of androgen deprivation therapy outweigh the potential risk ofcardiovascular events.