This trial is designed to determine whether an 8-week course of escalated dose conformal radiation can be compressed safely, and with similar efficacy into a 4-week course.

In this trial, men with intermediate risk prostate cancer will be randomized to a shorter course of radiotherapy (6000cGy in 20 fractions over 4 weeks-hypofractionated) or treatment with a conventional fractionation course (7800cGy in 39 fractions over 8 weeks-standard). Three-dimensional conformal radiation treatment techniques, including intensity modulated radiotherapy will be used for both hypofractionated and standard treatments to avoid normal tissue exposure to radiation and minimize the risk of acute and late treatment related toxicity. The primary outcome measure is biochemical (PSA) failure defined by the ASTRO consensus criteria. Secondary outcomes include biochemical-clinical failure (BCF), mortality from cancer, toxicity and health-related quality of life. It is planned to recruit 1204 patients to the study. If the safety and efficacy of the shorter course are demonstrated, then its adoption would reduce the social, emotional and economic burden of treatment for patients and their families.

Inclusion Criteria:

1. Histologic diagnosis of carcinoma of the prostate within 6 months of entry without evidence of metastatic disease to the lymph nodes, bone or lung;
2. Intermediate risk prostate cancer (that is, T1-2a, Gleason score <6, PSA 10.1-20.0 ng/ml; T2b-c Gleason <6, PSA ≤ 20.0 ng/ml; T1-2, Gleason 7, PSA ≤ 20.0 ng/ml).

Exclusion Criteria:

1. Histologic diagnosis of carcinoma of the prostate more than six months prior to study entry;
2. Previous therapy for carcinoma of the prostate other than biopsy or transurethral resection;
3. Patients previously on more than 12 weeks of hormone therapy for treatment of their prostate cancer;
4. Any other active malignancy (untreated, progressive or recurrent), except for non-melanoma skin cancer. Any inactive malignancy diagnosed within 5 years of entry, except for non-melanoma skin cancer;
5. Treatment plan cannot meet dose constraints for the hypofractionation arm of the trial;
6. Previous pelvic radiotherapy;
7. Inflammatory bowel disease.