Endoscopic Evaluation of Late Rectal Injury Following CyberKnife Radiosurgery for Prostate Cancer

Radiation therapy is a well-established treatment modality for clinically localized prostate
cancer. Current techniques include conventional external beam radiotherapy and intensity
modulated radiation therapy (IMRT). The efficacy of conventional external beam radiation
treatment (60-70 Gy in 2 Gy fractions) using several uniform fields has been documented. The
10-year disease-free survival rate for patients with disease confined to the prostate in the
pre-Prostate Specific Antigen (PSA) era was approximately 50-70%. Analysis of these data
suggested that dose escalation could improve local control in prostate cancer.

On average, men who choose to undergo radiation therapy treatments for prostate cancer will
have to live with the side effects of therapy for many years. Chronic proctitis may occur
after radiotherapy (RT) to the pelvic region. According to a published series, it clinically
occurs after radiation therapy of localized prostate cancer at a frequency of 5-20%. It
occurs months to years after treatment (average 8-12 months) with a large majority within two
years following radiation therapy. Patient characteristics, such as a history of inflammatory
bowel disease or chronic anticoagulation therapy, may increase an individual patient's risk
of clinically significant proctitis. Patients with radiation-induced proctopathy have
described symptoms of rectal pain, diarrhea, urgency, rectal bleeding, and increased
frequency of bowel movements. Endoscopic evaluation shows telangiectasia, congested mucosa
and ulcers. Rectal bleeding occurs from the neovascular telangiectasia seen in about 60% of
patients receiving conventionally fractionated radiation therapy. The other symptoms probably
develop from the decreased rectal compliance associated with rectal wall fibrosis. These
symptoms are, in current reports, most often classified according to the NCI Common Toxicity
Criteria grade for late gastrointestinal side effects. Due to the proximity of the rectum and
bladder to the prostate, using conventional techniques, the prescription dose is limited to
65-70 Gy. Although attempts were made to protect the rectum, the incidence of rectal bleeding
was unacceptable at doses greater than 70 Gy (20%).

The risk of proctitis and rectal bleeding appeared to be dependent upon both the radiation
dose and the volume of the rectum in the high dose area. Radiation Oncologists' efforts to
optimize the therapeutic ratio for prostate cancer treatment have therefore been directed
toward limiting the high dose volume to the prostate while escalation the dose within that
volume. Intensity modulated radiation therapy (IMRT) is a widely used technology to achieve
this goal. It is accomplished by modulating the radiation beam intensity within each
radiation field in accordance with an optimization algorithm. This has allowed greater
dose-escalation without evident increase in acute complications, although follow-up is too
short to fully assess control and complication rates. Whether IMRT will provide a degree of
conformity that proves to eradicate prostate cancer with a high probability while sparing
local structures is as yet unresolved.

Late Rectal Mucosal Injury Following CyberKnife RadioSurgery for Clinically Localized
Prostate Cancer. The type, extent and incidence of rectal mucosal injury following CyberKnife
radiosurgery are currently unknown. The severity of clinical proctitis following radiation
therapy is commonly documented using the NCI Common toxicity criteria/Radiation Therapy
Oncology Group/EORTC. Unfortunately, clinical proctitis has a low sensitivity for detecting
rectal mucosal injury. Endoscopy gives the most accurate estimate of the extent and incidence
of rectal mucosal injury. The Vienna rectoscopy score (VRS) was developed to quantify rectal
mucosal changes following radiation therapy. In this study, endoscopic evaluation of mucosal
damage from CyberKnife treatment will be documented and correlated with gastrointestinal side
effects and treatment planning parameters.

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the prostate (Biopsy within one year of
enrollment)

- Signed Study-Specific Consent

- PSA within 60 days of registration

- Baseline American Urological Association (AUA)/ International Prognostic Scoring
System (IPSS) score of < 20

- Candidate for screening colonoscopy

- Pretreatment Colonoscopy/lower endoscopy done

Exclusion Criteria:

- Prior pelvic radiotherapy

- Prior radical prostate surgery

- Recent (within 5 years) or concurrent cancers other than non-melanoma skin cancer

- Implanted hardware adjacent to the prostate that would prohibit appropriate treatment
planning and/or treatment delivery

- Inflammatory bowel disease