Randomized Trial of Adjuvant Hormonal Therapy in Surgically Treated Prostate Cancer Patients at High Risk for Recurrence

OBJECTIVES:

- Determine the effect of one year of adjuvant hormonal ablation on disease-free survival
at 5 years in node-negative radical prostatectomy patients at high risk for
progression.

- Determine the effect of this treatment on the incidence of androgen independent
prostate cancer and on disease specific and overall survival.

- Determine the impact of one year of total androgen ablation on quality of life and
serum testosterone levels.

- Assess differences in quality of life between wives of patients in the androgen
ablation condition compared to wives of patients in the control condition.

- Obtain blood samples from patients at high risk for failure post-prostatectomy to
evaluate serum markers of prognosis.

OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms.

- Arm I: Patients receive leuprolide intramuscularly once every 3 months and oral
flutamide three times daily for 1 year.

- Arm II: Patients receive no initial treatment. Quality of life is assessed every 6
months for 5 years. Quality of life of wives/partners of patients is assessed every 6
months for two years.

Patients are followed every 3 months for 1 year and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 496 patients (248 per treatment arm) will be accrued for this
study within 3.5 years.

Inclusion Criteria:

1. Organ confined prostate cancer (stage T1-T2c) subsequent to clinical staging

2. Radical prostatectomy and bilateral lymph node dissection performed

3. Pathologic assessment of surgical specimens by MDACC pathologist

4. High risk of clinical or biochemical failure post prostatectomy (must fulfill one of
the following criteria): pathology; a) Gleason grade sum score greater than or equal
to 8, b) Seminal vesicle involvement, c) Extraprostatic extension with positive
surgical margins and Gleason greater than or equal to 7

5. Radical prostatectomy performed within 90 days of enrollment and serum PSA level <
0.1ng/ml

6. Written informed consent

Exclusion Criteria:

1. Any evidence of metastatic disease confirmed prior to enrollment

2. Inability to confirm pathologic risk factors or inadequate prostatectomy (see item
4.1.5).

3. Hormonal ablation for greater than 3 months or radiotherapy for prostate cancer

4. Failure to achieve prostate specific antigen level of less than 0.1ng/ml prior to
enrollment in study

5. Elevation of liver function tests 2x normal

6. Contraindication to the use of LH-RH agonists or antiandrogens

7. Active secondary malignancy (other than squamous or basal cell skin cancer) within
five years prior to enrollment in study

8. Any concomitant medical condition that would make it undesirable for the 7patient to
participate in the trial or jeopardize compliance with the protocol