Radiation Therapy Followed by Surgery in High-Risk, Localized Carcinoma of the Prostate

A Phase I Dose-Escalation Study of Preoperative Radiation Therapy Followed by Radical Prostatectomy in Patients With High-Risk, Localized Carcinoma of the Prostate

The purpose of the study is to assess the safety of four different doses of radiation therapy followed by to surgery to remove prostate tumor.

Patients in Groups 1 and 2 will receive 39.6 Gy and 45 Gy (at 1.8 Gy/fraction), respectively, to the whole pelvis. Patients in Groups 3 and 4 will receive 45 Gy to the whole pelvis, followed by a boost to the prostate and periprostatic tissue, for total doses of 50.4 and 54 Gy, respectively. The patients will then undergo radical prostatectomy between 4-8 weeks after completion of radiation.

Inclusion Criteria:

• Subjects must have biopsy-confirmed adenocarcinoma of the prostate.
• Subjects must have a negative bone scan.
• Subjects must have "high-risk" prostate cancer, defined as:

A. PSA >/= 20, and/or B. Gleason Score (GS) >/= 8, and/or C. Clinical stage T3 disease per AJCC Staging Manual, 6th edition; or D. At least two out of three of the following: PSA 10-19.9, GS = 7, or clinical stage = T2b / T2c.

• Subjects must be medically fit to undergo surgery as determined by treating urologist.
• Subjects must be under 70 years of age.
• KPS must be >/= 80.
• Subjects must not have a synchronous primary tumor, or a previous cancer unless disease free for >/= 5 years.
• Subjects must not have had prior pelvic radiation therapy, chemotherapy, or androgen deprivation.
• Subjects must freely sign informed consent to enroll in the study.

Exclusion Criteria:

• Metastatic disease as demonstrated by bone scan, CT scan or MRI of the pelvis, or chest x-ray.
• Pathologically documented positive pelvic lymph nodes. If Pre-operative CT scan or MRI (ordered at the discretion of the treating physicians) demonstrates lymph nodes which are suspicious for involvement, then biopsy must be undertaken and nodes proven negative before patient can enroll on this trial.
• Declared high-risk for anesthesia by attending anesthesiologist, cardiologist, or other physician.
• History of prior pelvic radiation therapy.
• History of androgen deprivation therapy or chemotherapy.