A Phase III Intensity Radiotherapy Dose Escalation for Prostate Cancer Using Hypofractionation

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 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.