The purpose of this study is to determine whether vaccination with the Ad/PSA vaccine will induce an anti-PSA immunity that will result in the destruction of the remaining prostate cancer cells.

Subjects will be randomized to Arm A (vaccine only) or Arm B (androgen deprivation therapy plus vaccine). On Arm A, subjects can begin the three vaccinations immediately. On Arm B, subjects will be started on androgen deprivation therapy (ADT) 14 days prior to beginning the vaccinations.

Subjects will be vaccinated three times, each injection administered at 30-day intervals. Based upon our earlier clinical trial, the vaccine is considered safe and should not induce any major side effects. The investigators hope that vaccination with this PSA virus will cause the body to produce immunity to the PSA and that immunity will destroy any cell that produces PSA. Since the only cells left in the body that produce PSA will be the cancer cells, the investigators propose that the vaccination and ensuing anti-PSA immunity will kill the prostate cancer cells. Importantly, this treatment should not cause any major side effects as would treatment with anti-cancer drugs.

Inclusion Criteria:

• Men with prostate cancer who have received prior local therapy (radical prostatectomy or definitive radiation therapy) and have biochemical (PSA) relapse without evidence of radiographic or clinical metastatic disease.
• For men who had prior prostatectomy, the surgery must have occurred at least 6 months prior to initiation of treatment.
• For men who had prior definitive radiation therapy, radiation must have been completed at least 1 year prior to initiation of treatment.
• Exhibit at least three separate rises in serum PSA, at least one month apart with differences >/= 0.03 ng/ml and a total PSA of >0.2 ng/ml.
• Have a PSA doubling time of >/= 6 months if the baseline serum PSA was >2 ng/ml.
• Negative bone scans.
• Negative CT scans of abdomen and pelvis (no evidence of soft tissue lesions >/= 1 cm).
• Scans must be obtained within 6 weeks of entry into the trial (initiation of treatment).
• Written informed consent.
• Age >/= 18 years.
• Required laboratory values [obtained within 2 weeks of study entry (initiation of treatment)].
• Serum creatinine </= 2.0 mg/dL
• Adequate hematologic function: granulocytes >/= 1800 per mm3, platelets >/= 100,000 per mm3, WBC >/= 3700, and lymphocytes >/= 590.
• Adequate hepatocellular function: AST <3x upper limit of normal and bilirubin <1.5 mg/dl (unless bilirubin elevation is consistent with Gilbert's syndrome).
• PSA used as an eligibility criterion must be drawn within 42 days prior to injection number 1 and will be redrawn on Day 1 for use as a baseline value.

Exclusion Criteria:

• Candidates for salvage radiation therapy unless the patient refuses.
• Active or unresolved clinically significant infection.
• Parenteral antibiotics <7 days prior to initiation of treatment.
• Evidence of prior or current CNS metastases. Specific imaging is not necessary in the absence of signs or symptoms.
• Co-morbid medical conditions which would result in a life expectancy (participation) of less than 1 year.
• Patients with compromised immune systems; congenital, acquired, or drug-induced (immunosuppressive agents) will be excluded from the study. Use of prednisone at doses higher than 10 mg daily (or equipotent steroid doses) for more than 7 days within the last 3 months is not allowed.
• No-pre-existing malignancies that required treatment within the past 5 years except for basal or squamous cell cancers of the skin.
• Prior systemic therapies for prostate cancer not allowed (hormonal therapy, including but not limited to LHRH agonists, antiandrogens, ketoconazole or chemotherapy - mitoxantrone/taxanes/estramustine, etc.) except when patients stopped hormone therapy two or more years prior to enrollment and currently have normal testosterone levels; patients in Arm B, undergoing androgen depletion therapy during the vaccination will be eligible.
• Prior participation in any vaccine studies for non-infectious diseases.
• The inability to understand the language and the clinical protocol.
• Allergy or religious objection to pork products; Gelfoam is produced from pork.

All-Cause Mortality was collected and assessed every 6 months via phone and then via medial record review during long-term follow-up, up to 14 years, AEs collected and recorded at least 4 weeks (30 days) after the last exposure to the study drug (up to day 90).