Prostate Cancer, Psychosocial Effects of Cancer and Its Treatment, Radiation Toxicity, Sexual Dysfunction
Conditions
Keywords
radiation toxicity, sexual dysfunction, psychosocial effects of cancer and its treatment, adenocarcinoma of the prostate, stage I prostate cancer, stage IIA prostate cancer
Brief summary
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.
Detailed description
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.
Interventions
RADIATION36.25 Gy IMRT
36.25 Gy in 5 fractions of 7.5 Gy twice a week over 15-17 days. A minimum of 72 hours and a maximum of 96 hours will separate each treatment. IMRT or similar techniques that use inverse treatment planning or protons are required.
RADIATION51.6 Gy IMRT
51.6 Gy in 12 fractions of 4.3 Gy 5 days a week over 16-18 days. IMRT or similar techniques that use inverse treatment planning or protons are required.
Sponsors
National Cancer Institute (NCI)
NRG Oncology
Radiation Therapy Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Reduction From Baseline to the One-year EPIC Bowel Domain Score That Exceeds 5 Points | Baseline and one year from the end of protocol treatment | 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. |
| The Percentage of Patients With Reduction From Baseline to One-year EPIC Urinary Domain Score That Exceeds 2 Points | Baseline and one year from the end of protocol treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Disease-free Survival (DFS) | Registration to 5 years | 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. |
| Mean Quality Adjusted Life Years at 5 Years | Registration to 5 years from the end of protocol treatment | 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. |
| Change From Baseline in EPIC Bowel and Urinary HRQOL as Continuous Variables at One Year | Baseline and one year from the end of protocol treatment | 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. |
| The Percentage of Patients With Reduction From Baseline at One Year in EPIC Sexual Domain Score That Exceeds 11 Points | Baseline one year from the end of protocol treatment | 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. |
| Acute and Late Gastrointestinal (GI) and Genitourinary (GU) Toxicity for Each Arm | Start of protocol treatment to one year from the end of protocol treatment | 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. |
| Change From Baseline in EQ-5D Scores | Baseline and one year from the end of protocol treatment | 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. |
| Utilization of Sexual Medications/Devices Questionnaire Response Frequences | Baseline and one year from the end of protocol treatment | 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. |
| Genetic Markers Associated With Normal Tissue Toxicities Resulting From Radiotherapy | Study entry to 5 years 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 | Baseline and one year from the end of protocol treatment | 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. |
| Rate of PSA Failure | Registration to five years | 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 5 Fractions 36.25 Gy IMRT in 5 fractions over two and a half weeks | 119 |
| 12 Fractions 51.6 Gy IMRT in 12 fractions over two and a half weeks | 121 |
| Total | 240 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | No protocol treatment | 2 | 4 |
| Overall Study | Protocol Violation | 6 | 3 |
Baseline characteristics
| Characteristic | 5 Fractions | 12 Fractions | Total |
|---|---|---|---|
| Age, Continuous | 64 years | 66 years | 65 years |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 119 Participants | 121 Participants | 240 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 101 / 119 | 106 / 121 |
| serious Total, serious adverse events | 1 / 119 | 0 / 121 |
Outcome results
Primary
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
Population: Eligible patients who started protocol treatment and completed the bowel domain of the EPIC at baseline and one year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 Fractions | Percentage of Patients With Reduction From Baseline to the One-year EPIC Bowel Domain Score That Exceeds 5 Points | 30.1 percentage of participants |
| 12 Fractions | Percentage of Patients With Reduction From Baseline to the One-year EPIC Bowel Domain Score That Exceeds 5 Points | 28.0 percentage of participants |
Comparison: ≤35% was considered acceptable, ≥55% unacceptable. Each arm analyzed separately. Average score and standard error of each arm calculated and one-sample z-test for proportion with significance level of 0.025 was used. For a given arm, if the null hypothesis of p ≤ 0.35 is rejected, then conclude that the regimen given on that arm is unacceptable. However if it not rejected for both bowel \& urinary domains, then that regimen will be considered acceptable for further use in a Phase III study.p-value: 0.19One sample z-test
Comparison: ≤35% was considered acceptable, ≥55% unacceptable. Each arm analyzed separately. Average score and standard error of each arm calculated and one-sample z-test for proportion with significance level of 0.025 was used. For a given arm, if the null hypothesis of p ≤ 0.35 is rejected, then conclude that the regimen given on that arm is unacceptable. However if it not rejected for both bowel \& urinary domains, then that regimen will be considered acceptable for further use in a Phase III study.p-value: 0.08One sample z-test
Primary
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
Population: Eligible patients who started protocol treatment and completed the urinary domain of the EPIC at baseline and one year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 Fractions | The Percentage of Patients With Reduction From Baseline to One-year EPIC Urinary Domain Score That Exceeds 2 Points | 45.2 percentage of participants |
| 12 Fractions | The Percentage of Patients With Reduction From Baseline to One-year EPIC Urinary Domain Score That Exceeds 2 Points | 42.0 percentage of participants |
Comparison: ≤40% was considered acceptable, ≥60% unacceptable. Each arm analyzed separately. Average score and standard error of each arm calculated and one-sample z-test for proportion with significance level of 0.025 was used. For a given arm, if the null hypothesis of p ≤ 0.40 is rejected, then conclude that the regimen given on that arm is unacceptable. However if it not rejected for both bowel \& urinary domains, then that regimen will be considered acceptable for further use in a Phase III study.p-value: 0.18One sample z-test
Comparison: ≤40% was considered acceptable, ≥60% unacceptable. Each arm analyzed separately. Average score and standard error of each arm calculated and one-sample z-test for proportion with significance level of 0.025 was used. For a given arm, if the null hypothesis of p ≤ 0.40 is rejected, then conclude that the regimen given on that arm is unacceptable. However if it not rejected for both bowel \& urinary domains, then that regimen will be considered acceptable for further use in a Phase III study.p-value: 0.38One sample z-test
Secondary
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
Population: Eligible patients who started protocol treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5 Fractions | Acute and Late Gastrointestinal (GI) and Genitourinary (GU) Toxicity for Each Arm | Acute | 1.7 percentage of participants |
| 5 Fractions | Acute and Late Gastrointestinal (GI) and Genitourinary (GU) Toxicity for Each Arm | Late | 0.8 percentage of participants |
| 12 Fractions | Acute and Late Gastrointestinal (GI) and Genitourinary (GU) Toxicity for Each Arm | Acute | 1.7 percentage of participants |
| 12 Fractions | Acute and Late Gastrointestinal (GI) and Genitourinary (GU) Toxicity for Each Arm | Late | 0.8 percentage of participants |
Secondary
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
Population: Eligible patients who started protocol treatment and completed the respective domain of the EPIC at baseline and one year
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 5 Fractions | Change From Baseline in EPIC Bowel and Urinary HRQOL as Continuous Variables at One Year | 1-year Bowel | 1.79 units on a scale |
| 5 Fractions | Change From Baseline in EPIC Bowel and Urinary HRQOL as Continuous Variables at One Year | 1-year Urinary | 0 units on a scale |
| 12 Fractions | Change From Baseline in EPIC Bowel and Urinary HRQOL as Continuous Variables at One Year | 1-year Bowel | 0 units on a scale |
| 12 Fractions | Change From Baseline in EPIC Bowel and Urinary HRQOL as Continuous Variables at One Year | 1-year Urinary | 0 units on a scale |
Comparison: \[Bowel one-year results\] Originally the t-test was planned to test if the change in each arm is different from 0. Wilcoxon Mann-Whitney was used instead due to the normality of the data.p-value: 0.03Wilcoxon (Mann-Whitney)
Comparison: \[Bowel one-year results\] Originally the t-test was planned to test if the change in each arm is different from 0. Wilcoxon Mann-Whitney was used instead due to the normality of the data.p-value: 0.03Wilcoxon (Mann-Whitney)
Comparison: \[Urinary one-year results\] Originally the t-test was planned to test if the change in each arm is different from 0. Wilcoxon Mann-Whitney was used instead due to the normality of the data.p-value: 0.09Wilcoxon (Mann-Whitney)
Comparison: \[Urinary one-year results\] Originally the t-test was planned to test if the change in each arm is different from 0. Wilcoxon Mann-Whitney was used instead due to the normality of the data.p-value: 0.43Wilcoxon (Mann-Whitney)
Secondary
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
Population: All eligible patients who started study treatment and completed the EQ-5D at baseline and the specified timepoint
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 5 Fractions | Change From Baseline in EQ-5D Scores | 1-year Index Score | 0 units on a scale |
| 5 Fractions | Change From Baseline in EQ-5D Scores | 1-year VAS | 0 units on a scale |
| 12 Fractions | Change From Baseline in EQ-5D Scores | 1-year Index Score | 0 units on a scale |
| 12 Fractions | Change From Baseline in EQ-5D Scores | 1-year VAS | 0 units on a scale |
Comparison: \[One-year Index Score\] Originally the t-test was planned to test if the change in each arm is different from 0. Wilcoxon Mann-Whitney was used instead due to the non-normality of the data. Each arm analyzed separately.p-value: 0.16Wilcoxon (Mann-Whitney)
Comparison: \[One-year Index Score\] Originally the t-test was planned to test if the change in each arm is different from 0. Wilcoxon Mann-Whitney was used instead due to the non-normality of the data. Each arm analyzed separately.p-value: 0.03Wilcoxon (Mann-Whitney)
Comparison: \[One-year VAS Score\] Originally the t-test was planned to test if the change in each arm is different from 0. Wilcoxon Mann-Whitney was used instead due to the non-normality of the data. Each arm analyzed separately.p-value: 0.83Wilcoxon (Mann-Whitney)
Comparison: \[One-year VAS Score\] Originally the t-test was planned to test if the change in each arm is different from 0. Wilcoxon Mann-Whitney was used instead due to the non-normality of the data. Each arm analyzed separately.p-value: 0.86Wilcoxon (Mann-Whitney)
Secondary
Genetic Markers Associated With Normal Tissue Toxicities Resulting From Radiotherapy
Time frame: Study entry to 5 years from the end of protocol treatment
Population: The biomarker data will not be obtained due to lack of funding therefore no patients have outcome measure data.
Secondary
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
Population: Eligible patients who started protocol treatment with baseline EQ-5D and at least 1 follow-up assessment (EQ-5D Index Score)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 Fractions | Mean Quality Adjusted Life Years at 5 Years | 6.13 quality-adjusted life years | Standard Deviation 10.55 |
| 12 Fractions | Mean Quality Adjusted Life Years at 5 Years | 4.87 quality-adjusted life years | Standard Deviation 1.14 |
Secondary
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
Population: Eligible patients who started protocol treatment and were at risk at the given time point
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5 Fractions | Rate of Disease-free Survival (DFS) | One year | 99.2 percentage of participants |
| 5 Fractions | Rate of Disease-free Survival (DFS) | Two years | 99.2 percentage of participants |
| 5 Fractions | Rate of Disease-free Survival (DFS) | Five years | 89.6 percentage of participants |
| 12 Fractions | Rate of Disease-free Survival (DFS) | One year | 99.2 percentage of participants |
| 12 Fractions | Rate of Disease-free Survival (DFS) | Two years | 97.5 percentage of participants |
| 12 Fractions | Rate of Disease-free Survival (DFS) | Five years | 92.3 percentage of participants |
Secondary
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
Population: Eligible patients who started protocol treatment and were at risk at the given time point
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5 Fractions | Rate of PSA Failure | One year | 0.0 percentage of participants |
| 5 Fractions | Rate of PSA Failure | Two years | 0.0 percentage of participants |
| 5 Fractions | Rate of PSA Failure | Five years | 3.4 percentage of participants |
| 12 Fractions | Rate of PSA Failure | One year | 0.8 percentage of participants |
| 12 Fractions | Rate of PSA Failure | Two years | 0.8 percentage of participants |
| 12 Fractions | Rate of PSA Failure | Five years | 3.5 percentage of participants |
Secondary
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
Population: Eligible patients who started study treatment and completed the specified domain of the EPIC at baseline and one year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 Fractions | The Percentage of Patients With Reduction From Baseline at One Year in EPIC Hormonal Domain Score That Exceeds 3 Points | 36.7 percentage of participants |
| 12 Fractions | The Percentage of Patients With Reduction From Baseline at One Year in EPIC Hormonal Domain Score That Exceeds 3 Points | 38.1 percentage of participants |
Comparison: ≤38% was considered acceptable, ≥58% unacceptable. Each arm analyzed separately. Average score and standard error of each arm calculated and one-sample z-test for proportion with significance level of 0.025 was used.p-value: 0.44one sampe z-test
Comparison: ≤38% was considered acceptable, ≥58% unacceptable. Each arm analyzed separately. Average score and standard error of each arm calculated and one-sample z-test for proportion with significance level of 0.025 was used.p-value: 0.53One sample z-test
Secondary
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
Population: Eligible patients who started study treatment and completed the specified domain of the EPIC at baseline and one year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 Fractions | The Percentage of Patients With Reduction From Baseline at One Year in EPIC Sexual Domain Score That Exceeds 11 Points | 32.9 percentage of participants |
| 12 Fractions | The Percentage of Patients With Reduction From Baseline at One Year in EPIC Sexual Domain Score That Exceeds 11 Points | 30.4 percentage of participants |
Comparison: ≤35% was considered acceptable, ≥55% unacceptable. Each arm analyzed separately. Average score and standard error of each arm calculated and one-sample z-test for proportion with significance level of 0.025 was used.p-value: 0.39One-sample z-test
Comparison: ≤35% was considered acceptable, ≥55% unacceptable. Each arm analyzed separately. Average score and standard error of each arm calculated and one-sample z-test for proportion with significance level of 0.025 was used.p-value: 0.21One sample z-test
Secondary
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
Population: Eligible patients who started study treatment and completed the questionnaire at baseline and the specified timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5 Fractions | Utilization of Sexual Medications/Devices Questionnaire Response Frequences | Baseline penile prosthesis question | 6 participants |
| 5 Fractions | Utilization of Sexual Medications/Devices Questionnaire Response Frequences | 1-year Baseline medications/devices question | 25 participants |
| 5 Fractions | Utilization of Sexual Medications/Devices Questionnaire Response Frequences | Baseline medications/devices question | 30 participants |
| 5 Fractions | Utilization of Sexual Medications/Devices Questionnaire Response Frequences | 1-year penile prosthesis question | 2 participants |
| 12 Fractions | Utilization of Sexual Medications/Devices Questionnaire Response Frequences | 1-year Baseline medications/devices question | 29 participants |
| 12 Fractions | Utilization of Sexual Medications/Devices Questionnaire Response Frequences | Baseline penile prosthesis question | 7 participants |
| 12 Fractions | Utilization of Sexual Medications/Devices Questionnaire Response Frequences | 1-year penile prosthesis question | 5 participants |
| 12 Fractions | Utilization of Sexual Medications/Devices Questionnaire Response Frequences | Baseline medications/devices question | 29 participants |