Radiation Therapy in Treating Patients With Prostate Cancer

Radiation Therapy Oncology Group255 enrolled

Overview

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Given radiation therapy in different ways may kill more tumor cells. PURPOSE: This randomized phase II trial studies radiation therapy to see how well it works in treating patients with prostate cancer.

OBJECTIVES: Primary * To demonstrate that 1-year health-related quality of life (HRQOL) for at least one hypofractionated arm is not significantly lower than baseline as measured by the Bowel and Urinary domains of the Expanded Prostate Cancer Index Composite (EPIC) instrument. Secondary * To estimate the degree of change in HRQOL in each arm for the Sexual and Hormonal EPIC domains and the Utilization of Sexual Medications/Devices from baseline to 1 year, 2 years, and 5 years. * To estimate the degree of change in global HRQOL in each arm as measured by the Euro Quality of Life, 5 dimensions (EQ-5D) from baseline to 1 year, 2 years, and 5 years. * To estimate the rate of acute and late gastrointestinal (GI) and genitourinary (GU) toxicity for each arm at 1, 2, and 5 years. * To estimate prostate-specific antigen (PSA) failure in each arm at 1, 2, and 5 years. * To estimate disease-free survival (DFS) in each arm at 1, 2, and 5 years. * To estimate Quality Adjusted Life Years for each arm at 1, 2, and 5 years using the EQ-5D and DFS. * To identify genetic markers associated with normal tissue toxicities resulting from radiotherapy. * To collect tumor tissue for biomarker studies. * To estimate EPIC bowel and urinary HRQOL as continuous variables. OUTLINE: This is a multicenter study. Patients are stratified according to treatment techniques/machine (all linear accelerator-based treatment \[excluding cyberknife\] vs cyberknife vs protons). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients undergo hypofractionated radiotherapy using intensity-modulated radiation therapy (IMRT), cyberknife, or protons twice a week for approximately 2½ weeks (36.25 Gy total). * Arm II: Patients undergo hypofractionated radiotherapy using IMRT, cyberknife, or protons once a day, 5 days a week, for approximately 2½ weeks (51.6 Gy total). Patients may undergo blood and tumor tissue collection for correlative studies. Patients may also complete the Utilization of Sexual Medications/Devices, the European Questionnaire-5D, and the Bowel and Urinary domains of the Expanded Prostate Cancer Index Composite (EPIC) questionnaires at baseline and at 1, 2, and 5 years after completion of radiation therapy. After completion of study therapy, patients are followed-up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

DISEASE CHARACTERISTICS: * Histologically confirmed diagnosis of adenocarcinoma of the prostate within 180 days of randomization * History/physical examination with digital rectal examination of the prostate within 60 days prior to registration * Histological evaluation of prostate biopsy with assignment of a Gleason score to the biopsy material; Gleason scores 2-6 within 180 days of randomization * Clinical stage T1-2a (AJCC 7th edition) within 90 days of randomization * Prostate-specific antigen (PSA) \< 10 ng/mL within 60 days prior to registration; * PSA should not be obtained within 10 days after prostate biopsy * No evidence of distant metastases * No regional lymph node involvement PATIENT CHARACTERISTICS: * Zubrod performance status 0-1 * Willingness and ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire * No prior or concurrent invasive malignancy (except non-melanomatous skin cancer) or lymphomatous/hematogenous malignancy unless continually disease-free for a minimum of 5 years (for example, carcinoma of the oral cavity is permissible; however, patients with prior history of bladder cancer are not allowed) * No severe, active co-morbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects * Laboratory tests for liver function and coagulation parameters are not required for entry into this protocol * Acquired Immune Deficiency Syndrome (AIDS) based upon current Center for Disease Control (CDC) definition * HIV testing is not required for entry into this protocol * Protocol-specific requirements may also exclude immuno-compromised patients PRIOR CONCURRENT THERAPY: * No prior radical surgery (prostatectomy), cryosurgery, or high-intensity focused ultrasonography (HIFU) for prostate cancer * No prior pelvic irradiation, prostate brachytherapy, or bilateral orchiectomy * No prior hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH) agonists (e.g., goserelin, leuprolide) or LHRH antagonists (e.g., degarelix), anti-androgens (e.g., flutamide, bicalutamide), estrogens (e.g., diethylstilbestrol (DES)), or surgical castration (orchiectomy) * No finasteride within 30 days prior to registration * Prostate-specific antigen (PSA) should not be obtained prior to 30 days after stopping finasteride * No dutasteride within 90 days prior to registration * PSA should not be obtained prior to 90 days after stopping dutasteride * No prior or concurrent cytotoxic chemotherapy for prostate cancer * Patients on Coumadin or other blood-thinning agents are eligible for this study * No concurrent 3D-conformal radiation therapy

Locations (37)

UAB Comprehensive Cancer Center

Birmingham, Alabama, United States

Arizona Center for Cancer Care - Peoria

Peoria, Arizona, United States

Arizona Oncology Services Foundation

Phoenix, Arizona, United States

Kaiser Permanente - Division of Research - Oakland

Oakland, California, United States

Rohnert Park Cancer Center

Rohnert Park, California, United States

Outcomes

Primary Outcomes

Percentage of Patients With Reduction From Baseline to the One-year EPIC Bowel Domain Score That Exceeds 5 Points

The co-primary endpoint is the percentage of patients with a reduction in the Expanded Prostate Cancer Index Composite (EPIC) bowel domain score from baseline to 1 year that exceeds 5 points (baseline - one year \> 5). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.

Time frame: Baseline and one year from the end of protocol treatment

The Percentage of Patients With Reduction From Baseline to One-year EPIC Urinary Domain Score That Exceeds 2 Points

The co-primary endpoint is the proportion of patients with a reduction in the Expanded Prostate Cancer Index Composite (EPIC) urinary domain score from baseline to 1 year that exceeds 2 points (baseline - one year \> 2). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.

Time frame: Baseline and one year from the end of protocol treatment

Secondary Outcomes

Acute and Late Gastrointestinal (GI) and Genitourinary (GU) Toxicity for Each Arm

Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. An acute adverse event is defined as the first occurrence of worst severity of the adverse event ≤30 days after the completion of radiation therapy (RT). The high dose RT arm of Radiation Therapy Oncology Group (RTOG) study RTOG-0126 (NCT00033631) reported 1% of patients experienced grade 3+ GI/GU acute toxicity with no patient experiencing a grade 4 or 5 toxicity. If the lower confidence interval is \>1%, then that arm will be further investigated for acceptability. A late adverse event is defined as the first occurrence of worst severity of adverse event \>30 days after RT completion. Arms are not compared to each other.

Time frame: Start of protocol treatment to one year from the end of protocol treatment

Rate of PSA Failure

Failure occurs when the PSA is first noted to be 2 ng/mL or more than the current nadir value (PSA \> current nadir + 2) post RT completion. Time to PSA failure is defined as time from registration to the date of PSA failure, last known follow-up (censored), or death without PSA failure (competing risk). Rate of PSA failure is estimated by the cumulative incidence method. The protocol specified that one-, two-, and five-year rates would be reported. Arms are not compared to each other.

Time frame: Registration to five years

Rate of Disease-free Survival (DFS)

Disease-free survival duration is time from the date of randomization to the date of documentation of disease progression or until the date of death from any cause (censored). DFS is estimated by the Kaplan-Meier method. The protocol specified that one-, two-, and five-year rates would be reported. Arms are not compared to each other.

Time frame: Registration to 5 years

Mean Quality Adjusted Life Years at 5 Years

Quality-adjusted survival time combines disease-free survival time and quality of life as measured by the EuroQol 5-dimensional (EQ-5D) index score. It is calculated for each patient as the weighted sum of different time episodes and added up to total quality-adjusted life years . The EQ-5D measures health-related quality of life and consists of two parts, a general health visual analog scale and 5 general health questions. The latter questions are transformed into a single index score ranging from 0 (worst health state) to 1 (best health state). Arms are not compared to each other.

Time frame: Registration to 5 years from the end of protocol treatment

Change From Baseline in EPIC Bowel and Urinary HRQOL as Continuous Variables at One Year

The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life and a positive change from baseline indicating improvement over time. For this endpoint, in each domain, the actual change score calculated as timepoint score - baseline score will be used as the statistic.

Time frame: Baseline and one year from the end of protocol treatment

The Percentage of Patients With Reduction From Baseline at One Year in EPIC Sexual Domain Score That Exceeds 11 Points

The percentage of patients with a reduction in the EPIC sexual domain score from baseline that exceeds 11 points (baseline - one year \> 11). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.

Time frame: Baseline one year from the end of protocol treatment

The Percentage of Patients With Reduction From Baseline at One Year in EPIC Hormonal Domain Score That Exceeds 3 Points

The percentage of patients with a reduction in the EPIC hormonal domain score from baseline that exceeds 3 points (baseline - one year \> 3). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.

Time frame: Baseline and one year from the end of protocol treatment

Change From Baseline in EQ-5D Scores

The EQ-5D is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). Health states are defined by the combination of the leveled responses to the 5 dimensions, generating 243 health states to which unconsciousness and death are added. The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). Change from baseline is calculated as score at the timepoint of interested - baseline score. One, 2, and 5 years will be entered when they are available. Arms are not compared.

Time frame: Baseline and one year from the end of protocol treatment

Utilization of Sexual Medications/Devices Questionnaire Response Frequences

The Utilization of Sexual Medications/Devices questionaire is designed to assess the use of erectile aids among patients treated for prostate cancer. This instrument is used to complement the sexual symptom domain in the EPIC. The number of subjects responding "Yes" to the following questions are reported: "Do you have a penile prosthesis", "Have you used an medications or devices to aid or improve erections?". Arms are not compared to each other. One, 2, and 5 years will be entered when they are available.

Time frame: Baseline and one year from the end of protocol treatment

Genetic Markers Associated With Normal Tissue Toxicities Resulting From Radiotherapy

Time frame: Study entry to 5 years from the end of protocol treatment

Radiation Therapy in Treating Patients With Prostate Cancer

Overview

Conditions

Interventions

Eligibility

Locations (37)

Outcomes

Primary Outcomes

Secondary Outcomes