Hypofractionated Radiation Therapy in Treating Participants With Prostate Cancer High-Risk Features Following Radical Prostatectomy

PRIMARY OBJECTIVES:

I. To determine if stereotactic body radiation therapy (SBRT) would result in similar freedom
from failure (FFF) than standard fractionation photon therapy.

SECONDARY OBJECTIVES:

I. After completion of radiation therapy, determine the incidence of grade 2 or greater
genitourinary (GU) and gastrointestinal (GI) toxicity at 6 months (Common Terminology
Criteria for Adverse Events [CTCAE] version 4).

II. After completion of radiation therapy, determine the incidence of grade 3 or greater GU
and GI toxicity at 6 months (CTCAE version 4).

III. After completion of radiation therapy, determine the incidence of quality of life issues
following completion of radiation therapy.

IV. After completion of radiation therapy, determine the incidence of impotence after the use
of radiation therapy at 3 years.

V. After completion of radiation therapy, determine the incidence of freedom from biochemical
failure (FFBF) at 5 years.

VI. After completion of radiation therapy, determine the incidence of clinical failure: local
and/or distant at 5 years.

VII. After completion of radiation therapy, determine the incidence of salvage androgen
deprivation use (SAD) at 5 years.

VIII. After completion of radiation therapy, determine the incidence of progression free
survival: using clinical, biochemical and SAD as events at 5 years.

IX. After completion of radiation therapy, determine the incidence of overall survival at 5
years.

X. After completion of radiation therapy, determine the incidence of disease-specific
survival at 5 years.

XI. Determine the impact of radiation therapy on quality of life. XII. Determine overall GI
and GU toxicity. XIII. Determine prostate and normal structure movement during radiation
therapy (RT) with the use of scans.

XIV. Correlate pathologic and radiologic findings with outcomes. XV. Correlate pre-RT
prostate specific antigen (PSA) levels with outcomes. XVI. Correlate variation in proton
therapy or x-ray dosimetry and outcomes. XVII. Develop a quality assurance process for
prostate proton therapy. XVIII. Prospectively collect information that will help to define
dose-volume relationships of normal structures with acute and chronic toxicity.

XIX. Allow for future research of pathologic risk factors that may influence prognosis; this
information will help us to attempt to characterize their presence in prostate cancer with
high risk features after prostatectomy and their potential effect on outcomes.

XX. Possibly compare dosimetric parameters of an IMRT plan with the proton therapy radiation
plan.

OUTLINE: Participants are assigned to 1 of 3 groups.

GROUP I: Participants undergo hypofractionated radiation therapy over 15-30 minutes every
other day over 2 weeks, for 5 treatments.

GROUP II: Beginning 8-10 weeks before radiation therapy, participants receive androgen
suppression therapy subcutaneously (SC) or intramuscularly (IM) for up to 6 months (at the
discretion of the treating physician). Participants then undergo hypofractionated radiation
therapy as Group I.

GROUP III: Participants receive androgen suppression therapy as Group II for up to 18 months
(at the discretion of the treating physician), then undergo hypofractionated radiation
therapy over 15-30 minutes every other day over 1-2 weeks, for 1-5 treatments.

After completion of study treatment, participants are followed up at 3 and 12 months, every 6
months for 2 years, annually for 3 years, then biennially thereafter.

Inclusion Criteria:

- Histologically confirmed prostate adenocarcinoma at the time of surgery

- Pathologic stages T2-T3b, N0-Nx-N1, M0-1 as staged by the pathology report (American
Joint Committee on Cancer [AJCC] criteria 8th edition [Ed.])

- One or more high risk features including: seminal vesicle invasion, extracapsular
extension, positive margins, or a PSA post surgery between 0.2 and < 2.0

- PSA values < 2 ng/ml within 90 days prior to enrollment. Obtained at least 6 weeks
after surgery

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 assessed within 90
days of enrollment

- Patients must sign Institutional Review Board (IRB) approved study specific informed
consent

- Patients must complete all required pre-entry tests within the specified time frames

- Patients must be able to start treatment (androgen suppression [AS] or radiation)
within 120 days of study registration

- Positron emission tomography (PET) scan is suggested for a PSA >= 0.2 ngs/ml

- Magnetic resonance imaging (MRI) pelvis, computed tomography (CT) pelvic, or bone scan
for a PSA >= 0.2 ngs/ml may be done, based on the physician preference

- Members of all races and ethnic groups are eligible for this trial

- Patients from outside of the United States may participate in the study

Exclusion Criteria:

- Previous pelvic radiation

- Prior androgen suppression therapy for prostate cancer for more than 6 months

- Active rectal diverticulitis, Crohn?s disease affecting the rectum or ulcerative
colitis (non-active diverticulitis and Crohn?s disease not affecting the rectum are
allowed)

- Prior systemic chemotherapy for prostate cancer

- History of proximal urethral stricture requiring dilatation

- Current and continuing anticoagulation with warfarin sodium (coumadin), heparin, low-
molecular weight heparin, Clopidogrel bisulfate (plavix), or equivalent (unless it can
be stopped to manage treatment related toxicity, to have a biopsy if needed, or place
markers)

- Major medical, addictive or psychiatric illness which in the investigator?s opinion,
will prevent the consent process, completion of the treatment and/or interfere with
follow-up. (Consent by legal authorized representative is not permitted for this
study)

- Evidence of any other cancer within the past 5 years and < 50% probability of a 5 year
survival. (Prior or concurrent diagnosis of basal cell or non-invasive squamous cell
cancer of the skin is allowed)

- History of myocardial infarction or decompensated congestive heart failure (CHF)
within the last 6 months