The goal of this clinical research study is to find out how treatment with abiraterone acetate in combination with prednisone and a Luteinizing Hormone-Releasing Hormone (LHRH) analogue changes the tumor in comparison to treatment with an LHRH analogue alone.

Objectives:

Primary Objective:

To assess the difference in pathologic stage < pT2 between Group A and Group B.

Secondary Objective:

• To assess and compare the changes in levels of androgens (pre, during, and post treatment) in the serum, primary tumor microenvironment and bone marrow between Group A and Group B.
• To assess changes in biomarkers related to androgen signaling and other cancer-related pathways between Group A and Group B.
• To assess the difference in rate of positive surgical margins between Group A and Group B.
• To assess the safety profile of abiraterone acetate and low dose prednisone in a preoperative setting.

Study Groups:

Participants who are eligible to take part in this study will be randomly assigned (as in the flip of a coin) to 1 of 2 groups:

• Those who are in Group A will take abiraterone acetate, a LHRH analogue, and prednisone.
• Those who are in Group B will receive a LHRH analogue alone. Participants will have 2 out of 3 chances of being placed in Group A or 1 out of 3 chances of being placed in Group B.

Participants in both groups will receive the study drug(s) for about 3 months followed by a prostatectomy (prostate surgery) between 2 and 4 weeks after they stop taking the study drug(s).

Length of Study:

Participants will receive study drugs on this study for about 3 months before having surgery to remove their prostate about 2-4 weeks later. Participants will be removed from this study if the disease gets worse, if they experience intolerable side effects, or their study doctors feel that it is in their best interest to stop the study.

Long-Term Follow-Up:

Participants will return to the clinic 1 month, 3 months, 6 months, and then every 6 months (for up to 8 years) after your surgery for follow-up visits. Up to 66 patients will be take part in this study. All will be enrolled at M. D. Anderson after their surgery.

Inclusion Criteria:

1. Histological proof of prostatic adenocarcinoma via a minimum of 6 core biopsy samples
2. Clinical stage T1c or T2 with high-grade disease (Gleason's 8-10) on initial biopsy, or clinical stage T2b-T2c with Gleason's grade >/= 7 and PSA > 10ng/ml.
3. No evidence of metastatic disease as determined by CT scans and bone scans.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of </= 1
5. Patients should have adequate bone marrow function defined as an absolute peripheral granulocyte count (ANC) > 1,500 and platelet count of > 100,000.
6. Normal pituitary and adrenal function
7. Patients should be deemed to be candidates for radical prostatectomy.

Exclusion Criteria:

1. Histological variants in the primary tumor (histological variants other than adenocarcinoma); neuroendocrine tumor
2. Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection
3. Uncontrolled hypertension
4. Abnormal Liver function
5. Active or symptomatic viral hepatitis or chronic liver disease
6. Clinically significant heart disease
7. Other active malignancy
8. History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
9. Previous treatment with abiraterone acetate
10. Patients who are not appropriate surgical candidates for radical prostatectomy
11. Prior chemotherapy or radiation therapy for prostate cancer.
12. Condition or situation which, in the investigator's opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with patient's participation in the study

Note: There are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

3 years