CyberKnife Radiosurgery For Low & Intermediate Risk Prostate Cancer: Emulating HDR Brachytherapy Dosimetry

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effects of CyberKnife radiosurgery in patients with early stage organ-confined prostate cancer and to evaluate the effects of this treatment on the quality of life over time.

Detailed Description
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In this study, CyberKnife radiosurgery will be used to produce dose distributions comparable to those created by High Dose Rate (HDR) brachytherapy treatment, without the use of invasive catheters. The radiosurgery volumes will closely be made to resemble HDR brachytherapy therapeutic volumes with similar dose limitation objectives to adjacent normal tissues. The CyberKnife Robotic Radiosurgery System is a unique radiosurgical system capable of treating tumors anywhere in the body noninvasively and with sub-millimeter accuracy. The CyberKnife System delivers radiation using a precise targeting methodology allowing a focal treatment margin around the target, thus limiting the volume of adjacent tissue receiving high doses radiation. This in turn allows the delivery of high doses of radiation to the prostate over a short series of treatments.

Official Title
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Prospective Evaluation of CyberKnife Stereotactic Radiosurgery for Low and Intermediate Risk Prostate Cancer: Emulating HDR Brachytherapy Dosimetry

Conditions
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Prostate Neoplasms, Cancer of the Prostate, Prostate Cancer, Prostatic Cancer, Prostatic Neoplasms

Intervention / Treatment
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* Radiation: CyberKnife Stereotactic Radiosurgery - Low Risk
* Radiation: CyberKnife Stereotactic Radiosurgery - Intermediate Risk


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must be at least 18 years of age Histologically proven prostate adenocarcinoma Biopsy within 1 year of date of registration Clinical Stage (CS) T1b-T2b, N0, M0 Patients belonging to one of the following risk categories: Low Risk: CS T1b-T2a, Gleason Score 2-6, Prostate Specific Antigen (PSA) < or = 10 ng/ml Intermediate Risk: CS T2b, Gleason Score 2-6, PSA < or = 10 ng/ml or CS T1b-T2b, Gleason Score 2-6, PSA < or = 20 ng/ml or CS T1b-T2b, Gleason Score 7 and PSA < or = 10 ng/ml Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Exclusion Criteria: Clinical Stage T2c or greater Prior prostatectomy or cryotherapy of the prostate Prior radiotherapy of the prostate or lower pelvis Implanted hardware or other material that would prohibit appropriate treatment planning or delivery History of an invasive malignancy other than basal or squamous skin cancers in the last 5 years Hormone ablation for two months prior to enrollment or during treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Heterogeneous Dose<br>38 Gy delivered in 4 fractions of 9.5 Gy per fraction | Radiation: CyberKnife Stereotactic Radiosurgery - Low Risk<br>* 38 Gy delivered in 4 fractions of 9.5 Gy per fraction with a radial margin of 2 mm around the prostate<br>* Other names: CyberKnife;Radiation: CyberKnife Stereotactic Radiosurgery - Intermediate Risk<br>* 38 Gy delivered in 4 fractions of 9.5 Gy per fraction with a radial margin of 5mm posterolaterally<br>* Other names: CyberKnife;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk for Gastrointestinal (GI) and Genitourinary (GU) Toxicity | To estimate the rates of acute and late Grade 3-5 gastrointestinal and genitourinary toxicities (adverse events [AE]) observed in both low-risk and intermediate-risk cohorts during the 5 years following CyberKnife (CK) treatment for prostate cancer. Kaplan Meier estimates for 5-yr and 10-yr are reported. Adverse events occurring within 3 months of treatment were categorized as acute toxicities, and those developing after 3 months were considered late toxicities. The rates were determined using the first Grade 3 or higher adverse event per patient, reported as possibly, probably, or definitely related to CK treatment. The Common Toxicity Criteria for Adverse Events (CTCAE) Version 3.0 was used to determine the Grade or severity of adverse events in this study, with Grade 3 being severe or medically significant but not immediately life-threatening, Grade 4 being life-threatening and Grade 5 being death related to the adverse event. | Primary Safety Endpoint was measured at 5 years. Sites and patients had the option of continuing follow-up through 10 years. | 
| Biochemical Disease-Free Survival (bDFS) | To determine the rate of biochemical Disease-Free Survival (bDFS), using the Phoenix definition, following CyberKnife treatment. Kaplan Meier survival curves for bDFS were created and the 5-yr and 10-yr percentages are reported. The Phoenix definition uses a Prostate Specific Antigen (PSA) value exceeding the patients lowest PSA value (nadir) + 2 ng/mL as an indicator of disease recurrence. The percentage of patients who did not have such a PSA rise or receive any interventional therapy to treat prostate cancer are reported below. | Primary Efficacy Endpoint was measured at 5 years. Sites and patients had the option of continuing follow-up through 10 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control and Survival Outcomes | To determine the rates of local failure, distant failure, disease-free survival, disease-specific survival, and overall survival following CyberKnife treatment in prostate cancer patients. | Secondary outcomes were measured at 5 years. Sites and patients had the option of continuing follow-up through 10 years. | 
| Quality of Life Assessments: American Urological Association (AUA) Symptom Index (SI) | AUA-SI is a 7-item self-report measure used to assess urinary urgency, frequency, and voiding symptoms with scores ranging from 0 (no symptom) to 5 (symptom occurs almost always) Total score: 0-7 mild symptoms; 8-19 moderate symptoms; 20-35 severe symptoms | AUA questionnaire was completed at Baseline, CK Treatment, and post treatment at: 1 week, 1 month, 3 months, 6 months, and then biannually up to 5 years. Sites and patients had the option of continuing follow-up through 10 years. | 
| Quality of Life Assessments: Expanded Prostate Cancer Index Composite (EPIC) -26 Urinary Incontinence | EPIC-26 is a short form version of the Expanded Prostate Cancer Index Composite, and is a validated comprehensive instrument developed to measure the health-related quality of life among men with prostate cancer. EPIC-26 consists of 26 items under 5 domains of urinary incontinence, urinary irritative/obstructive, bowel, sexual, and hormonal. Answers qualitatively measure patient's bother for each symptom and are then normalized on a scale of 0 (worst) to 100 (best) to calculate domain scores if sufficient input is provided. | Secondary outcomes were measured at 5 years. Sites and patients had the option of continuing follow-up through 10 years. | 
| Quality of Life Assessments: EPIC-26 Urinary Irritative Obstructive | EPIC-26 is a short form version of the Expanded Prostate Cancer Index Composite, and is a validated comprehensive instrument developed to measure the health-related quality of life among men with prostate cancer. EPIC-26 consists of 26 items under 5 domains of urinary incontinence, urinary irritative/obstructive, bowel, sexual, and hormonal. Answers qualitatively measure patient's bother for each symptom and are then normalized on a scale of 0 (worst) to 100 (best) to calculate domain scores if sufficient input is provided. | Secondary outcomes were measured at 5 years. Sites and patients had the option of continuing follow-up through 10 years. | 
| Quality of Life Assessments: EPIC-26 Bowel | EPIC-26 is a short form version of the Expanded Prostate Cancer Index Composite, and is a validated comprehensive instrument developed to measure the health-related quality of life among men with prostate cancer. EPIC-26 consists of 26 items under 5 domains of urinary incontinence, urinary irritative/obstructive, bowel, sexual, and hormonal. Answers qualitatively measure patient's bother for each symptom and are then normalized on a scale of 0 (worst) to 100 (best) to calculate domain scores if sufficient input is provided. | Secondary outcomes were measured at 5 years. Sites and patients had the option of continuing follow-up through 10 years. | 
| Quality of Life Assessments: EPIC-26 Sexual | EPIC-26 is a short form version of the Expanded Prostate Cancer Index Composite, and is a validated comprehensive instrument developed to measure the health-related quality of life among men with prostate cancer. EPIC-26 consists of 26 items under 5 domains of urinary incontinence, urinary irritative/obstructive, bowel, sexual, and hormonal. Answers qualitatively measure patient's bother for each symptom and are then normalized on a scale of 0 (worst) to 100 (best) to calculate domain scores if sufficient input is provided. | Secondary outcomes were measured at 5 years. Sites and patients had the option of continuing follow-up through 10 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, CyberKnife, Stereotactic Radiosurgery, Radiosurgery, Prostate Tumor, Prostate Surgery