CyberKnife Stereotactic Radiosurgery for Low and Intermediate Risk Prostate Cancer

Due to advances in the ability to detect early stage prostate cancer better than before,
more men diagnosed with the disease are able to be cured. Methods of prostate cancer
treatment include having laparoscopic surgery, open surgery to remove the prostate,
receiving radiation therapy, or brachytherapy (placing high energy x-rays to destroy the
cancer cells). Although these treatment options have the potential to cure patients, these
treatments have drawbacks. The healing time following the removal of the prostate can be
substantial and local treatments from standard radiation and brachytherapy have potentially
negative long-term effects. The CyberKnife system is a new type of radiation machine that
uses a special system to precisely focus large doses of x-rays on the tumor. The device is
designed to concentrate large doses of radiation using robotic image guidance onto the tumor
specifically so that injury from radiation to the nearby normal tissue would be minimal. The
high doses of radiation directly to the tumor would provide a shorter series of treatments
and a faster recovery time. The purpose of this study is to determine the effects of
CyberKnife radiosurgery in patients with prostate cancer. The purpose of this evaluation is
to see if the treatment will help patients with low to intermediate risk prostate cancer and
to evaluate the effect of this treatment on the patients' quality of life over time.

Prior to entrance of this study patients will already have had their prostate specific
antigen (PSA) checked and a prostate biopsy within the last 6 months. To be included in the
study, the results of the biopsy must show that the patient has prostate cancer. In
addition, a patient will have a digital rectal exam (DRE) to determine if the cancer can be
felt. Based on the results of these tests and examination it has been determined that the
patient's prostate cancer is an early stage and has not likely spread outside the prostate
or anywhere else in his body. If the patient agrees to be in this study, he will be asked to
read and sign a consent form before having any procedure that is required for participation.
The patients will be asked to complete some short questionnaires before their CyberKnife
treatment. These questionnaires will ask multiple choice questions about the patient's
bowel, bladder and sexual function. They will also ask the patient some general questions
about his mood, activity and energy levels, and general health. The patient will also have a
physical examination and a procedure to place 3 to 5 small gold seeds into the prostate.
This procedure is commonly done in patients receiving standard external beam radiation (a
type of radiation treatment) for prostate cancer and is not an experimental procedure. These
gold markers will be used to determine the location of the prostate during the CyberKnife
treatment. An ultrasound probe is placed into the rectum and needles containing the gold
seeds are guided into the prostate and then the seeds are deposited. The patient will need
to clean out their rectum and take antibiotics the day of the seed placement. Within 5-10
days after placement of the gold seeds, the patient will be asked to return to the hospital
to have a planning CT scan (a procedure that takes 3 dimensional images) of the pelvis. This
is a regular CT scan and is standard procedure for patients receiving external beam
irradiation. The images obtained during the scan will be used to plan the CyberKnife
treatments. The patient will also have an MRI scan of the pelvis, unless medically
contraindicated (for example if they have a pacemaker) which will be used for treatment
planning purposes. The patient may be asked to undergo these scans with a urethral catheter
in place. The CyberKnife treatment will usually be started after the CT scan of the pelvis.
The patient's course of radiation will consist of 5 separate CyberKnife treatments usually
delivered over 5 week days (maximum 14 days), with no less than 12 hours between any two
fractions. Each treatment session will take approximately 1.5-2.5 hours. The patient will
lie on the treatment table and breathe normally while receiving radiation treatment. On the
last day of treatment a research team member will ask the patient questions about possible
side effects. After CyberKnife treatment, the patient will need follow-up visits to
determine how effective the treatment was and if they are having any treatment related side
effects. One to two weeks after treatment is completed, a member of the research team will
call the patient to see how they are doing. At 1 month after completion of the CyberKnife
treatment, the patient will be asked to return to the hospital for a follow-up examination
to check for any side effects. The patient will also be asked to complete the same
questionnaires they completed prior to CyberKnife treatment. These questionnaires will ask
about bowel, bladder and sexual function, as well as mood, activity and energy levels, and
general health. At 3 and 6 months after completion of the CyberKnife treatment, the patient
will be asked to return to their physician for an examination and a blood test to measure
PSA level. This is the standard procedure for follow-up visits and will occur every 6 months
thereafter for 5 years. At some of these visits, the patient will also be asked to complete
questionnaires about their bowel, bladder and sexual function as well as quality of life. If
it is suspected that the tumor is growing or if there are concerns about disease progression
on the patient's PSA exam, a prostate needle biopsy of the tumor may be performed.

Primary Objective: The primary safety goal of this study is to estimate, in both low-risk
and intermediate-risk cohorts, the rates of acute and late grade 3-5 gastrointestinal and
genitourinary toxicity observed following CyberKnife SABR for prostate cancer. The primary
efficacy goal is to document the rate of biochemical Disease-Free Survival (bDFS) using the
Phoenix and American Society of Radiation Oncology (ASTRO) definitions, at 5 years.

Secondary Objective: To measure the following in the study population: rates of local
failure, distant failure, disease-free survival, disease-specific survival, and overall
survival; quality of life (QOL) in generic and organ-specific domains.

Inclusion Criteria:

1. Histologically proven prostate adenocarcinoma

- Gleason score 2-7 (reviewed by reference lab)

- Biopsy within 6 months of date of registration

2. Clinical stage (CS) T1a-T2b, N0-Nx, M0-Mx (AJCC 6th Edition)

- T-stage and N-stage determined by physical exam and available imaging studies
(ultrasound, CT, and/or MRI)

- M-stage determined by physical exam, CT or MRI. Bone scan not required unless
clinical findings suggest possible osseous metastases.

3. PSA less than or equal to 20 ng/ml

4. Patients belonging in one of the following risk groups:

- Low: CS T1a-T2a and Gleason 2-6 and PSA less than or equal to 10, or

- Intermediate: CS T2b and Gleason 2-6 and PSA less than or equal to 10, or CS
T1b-T2b, and Gleason 2-6 and PSA less than or equal to 20 ng/ml, or Gleason 7
and PSA less than or equal to 10 ng/ml

5. Prostate volume less than or equal to 100 cc

- Determined using: volume = π/6 x length x height x width

- Measurement from CT or ultrasound less than or equal to 90 days prior to
registration

6. Eastern Cooperative Oncology Group (ECOG performance status 0-1

7. No prior prostatectomy or cryotherapy of the prostate

8. No prior radiotherapy to the prostate or lower pelvis

9. No implanted hardware or other material that would prohibit appropriate treatment
planning or treatment delivery, in the investigator's opinion.

10. Completion of patient questionnaires.

11. Consent signed.

12. Intermediate risk patients may be treated with 4-6 months of hormonal therapy at the
discretion of the treating physician.