The goal of this clinical research study is to compare using external beam radiotherapy with intensity modulated beams for fewer days at a higher dose per day to the same type of therapy for more days at a lower dose per day in the treatment of prostate cancer. The safety of these treatments will also be studied and compared.

Patients in this study will be randomly picked (as in the toss of a coin) to be in one of two treatment groups. There is an equal chance of being in either group.

Patients in Group 1 will be treated with intensity modulated radiotherapy (IMRT). These patients will receive 42 treatments, 5 days per week, over 8.5 weeks. This method has become the standard treatment at M.D. Anderson Cancer Center.

Patients in Group 2 will also be treated with IMRT. However, these patients will only receive 30 treatments, 5 days per week, over 6 weeks. The dose per day for Group 2 patients is higher than for Group 1 and has the possibility of killing more tumor cells.

Each external beam treatment requires about 10-20 minutes. However, patients can expect to spend 20 - 30 minutes on the treatment table because imaging measurements of prostate position will be done before each treatment. The total time in the radiation department each treatment day will be about an hour.

After the radiotherapy is completed, patients will have a PSA blood test every 3 months for 2 years, then every 6 months for Years 3 - 5, then annually. They will be examined every 6 months during the first 2 years beginning 3 months after the completion of treatment, then annually. A needle biopsy of the prostate will be performed if these tests suggest recurrence.

This is an investigational study. 225 patients will take part in this study. This study will take place at M. D. Anderson and possibly some affiliated hospitals.

Inclusion Criteria:

1. Biopsy proof of adenocarcinoma of the prostate.
2. Bone scan (If PSA >10 ng/ml or T3 disease) within 3 months of starting androgen ablation or signing protocol consent if no androgen ablation.
3. CT-scan of pelvis (If Stage T3 disease) within 3 months of starting androgen ablation or signing protocol consent if no androgen ablation.
4. Suitable medical condition; Zubrod <2.
5. Pretreatment PSA </=20 ng/ml. If PSA <4, must have Gleason greater than or equal to 7 and/or Stage T2b-T2c. PSA within 30 days of signing protocol consent. If neoadjuvant androgen ablation has been given, then the preandrogen ablation PSA should be used for stratification.
6. Clinical (palpable) Stage T1b - T3b disease (1992 AJCC staging system).
7. While a transrectal ultrasound will be obtained before treatment, the staging will not be based on these findings. If palpable T3 disease is present, then must have Gleason score <8 and pretreatment PSA less than or equal to 10 ng/ml
8. Gleason score <10.
9. If Gleason score 8 or 9, then must have stage T1/T2 disease and pretreatment PSA less than or equal to 10 ng/ml.
10. The patient must be able to understand the protocol and adhere to follow-up at 6-month intervals for the first 2 years and at yearly intervals thereafter.
11. Informed consent must be given.
12. Patients randomized to Arm 1 may also participate in protocol 2004-0428.

Exclusion Criteria:

1. Prior pelvic radiotherapy.
2. Greater than 4 months of prior hormone ablation therapy.
3. Prior or planned radical prostate surgery.
4. Clinical, radiographic or pathologic evidence of nodal or distant metastatic disease.
5. Concurrent, active malignancy, other than nonmetastatic skin cancer or early stage -chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for greater than or equal to 5 yr then the patient is eligible.
6. Zubrod status greater than or equal to 2.
7. Pretreatment PSA >20 ng/ml.
8. Gleason score of 10.
9. Palpable stage T3c (seminal vesicle involvement) or T4 disease.

8.5 years