Prostate Adenocarcinoma, Stage III Prostate Adenocarcinoma AJCC v7, Stage II Prostate Adenocarcinoma AJCC v7, Stage I Prostate Adenocarcinoma AJCC v7
Conditions
Brief summary
This randomized phase III trial studies how well hypofractionated radiation therapy works compared to conventional radiation therapy after surgery in treating patients with prostate cancer. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Conventional radiation therapy uses high energy x-rays, gamma rays, neutrons, protons, or other sources to kill tumor cells and shrink tumors. It is not yet known whether giving hypofractionated radiation therapy or conventional radiation therapy after surgery may work better in treating patients with prostate cancer.
Detailed description
PRIMARY OBJECTIVES: I. To demonstrate that hypofractionated post-prostatectomy radiotherapy (HYPORT) does not increase patient-reported gastrointestinal (GI) or genitourinary (GU) symptoms over conventionally fractionated post-prostatectomy (COPORT) at the 2-year time point. SECONDARY OBJECTIVES: I. To compare patient-reported GI symptoms using the Expanded Prostate Cancer Index Composite (EPIC)-26 at end of radiation therapy (RT) and 6, 12, 24, and 60 months from end of treatment. II. To compare patient-reported GU symptoms using the EPIC-26 at end of RT and 6, 12, 24, and 60 months from end of treatment. III. To compare time to progression (TTP) where progression is defined as the first occurrence of biochemical failure (BF), local failure, regional failure, distant metastasis (DM), institution of new unplanned anticancer treatment, or death from prostate cancer (prostate cancer specific mortality \[PCSM\]). IV. To compare freedom from biochemical failure (FFBF) and TTP rates with an alternate prostate specific antigen (PSA) \>= PSA nadir + 2 ng/mL definition of BF. V. To compare local failure, regional failure, salvage therapy (i.e. institution of new unplanned anticancer treatment), DM, PCSM, and overall survival (OS) rates. VI. Assessment of adverse events. EXPLORATORY OBJECTIVES: I. To compare utilities for health outcomes using the EuroQol five dimensions questionnaire (EQ-5D). II. Paraffin-embedded tissue block, serum, plasma, whole blood, and urine for future translational research analyses for predictors of toxicity following hypofractionated or conventionally fractionated post-prostatectomy radiotherapy. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo conventional radiation therapy for 37 fractions over 7 weeks in the absence of disease progression or unacceptable toxicity. Patients may also receive androgen deprivation therapy for up to 6 months as per doctor recommendation. ARM II: Patients undergo hypofractionated radiation therapy for 25 fractions over 5 weeks in the absence of disease progression or unacceptable toxicity. Patients may also receive androgen deprivation therapy for up to 6 months as per doctor recommendation. After completion of study treatment, patients are followed up every 6 months for 2 years and every year for 3 years and thereafter.
Interventions
RADIATIONHypofractionated Radiation Therapy
Undergo hypofractionated radiation therapy
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERQuality-of-Life Assessment
Ancillary studies
RADIATIONRadiation Therapy
Undergo conventional radiation therapy
Sponsors
NRG Oncology
National Cancer Institute (NCI)
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
* PRIOR TO STEP 1 REGISTRATION * Adenocarcinoma of the prostate treated primarily with radical prostatectomy * Any type of radical prostatectomy will be permitted, including retropubic, perineal, laparoscopic, or robotically assisted; there is no time limit for the date of radical prostatectomy * One of the following pathologic T-classifications: pT2 or pT3 * Patients with positive surgical margins are eligible * One of the following pathologic N-classifications: pN0, pNX * If a lymph node dissection is performed, the number of lymph nodes removed per side of the pelvis and the extent of the pelvic lymph node dissection (obturator versus \[vs.\] extended lymph node dissection) should be noted whenever possible * No clinical evidence of regional lymph node metastasis * Computed tomography (CT) (with contrast if renal function is acceptable; a noncontrast CT is permitted if the patient is not a candidate for contrast), magnetic resonance imaging (MRI), nodal sampling, or dissection of the pelvis within 120 days prior to step 1 registration * Patients with pelvic lymph nodes equivocal or questionable by imaging are eligible if the nodes are =\< 1 cm in the short axis * A post-radical prostatectomy study entry PSA \>= 45 days after prostatectomy and within 30 days prior to step 1, \< 2.0 ng/mL * No evidence of a local recurrence in the prostate fossa based on a digital rectal examination (DRE) within 60 days prior to step 1 registration * Patients with equivocal or questionable DRE findings should have an MRI of the pelvis to exclude the presence of a prostate fossa mass * Patients with equivocal or questionable exam findings by DRE or MRI are eligible if a biopsy of the lesion is negative for tumor * No evidence of bone metastases (M0) on bone scan (Na F positron emission tomography (PET)/CT is an acceptable substitute) within 120 days prior to step 1 registration * Equivocal bone scan findings are allowed if plain films and/or MRI are negative for metastasis * Zubrod performance status 0-1 within 60 days prior to step 1 registration * The patient or a legally authorized representative must provide study-specific informed consent prior to step 1 registration * Willingness and ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire * Only English and French-speaking patients are eligible to participate as these are the only language the EPIC has been validated in * PRIOR TO STEP 2 REGISTRATION * The EPIC must be completed in full and entered within 10 business days after step 1 registration; NRG Oncology Statistical and Data Management Center has 3 business days to score the results and send a notification to the site to proceed to step 2 randomization
Exclusion criteria
* A post-prostatectomy PSA nadir \>= 0.2 ng/mL AND Gleason \>= 7 (Considered for NRG-GU002, principal investigator \[PI\]: Hurwitz) * pT2 with a negative surgical margin and PSA \< 0.1 ng/mL * Androgen deprivation therapy started prior to prostatectomy for \> 6 months (180 days) duration; * Note: The use of finasteride or dutasteride (+/- tamsulosin) for longer periods prior to prostatectomy is acceptable * Androgen deprivation therapy started after prostatectomy and prior to step 1 registration for \> 6 weeks (42 days) * Neoadjuvant chemotherapy before or after prostatectomy * Prior invasive (except non-melanoma skin cancer) malignancy unless disease-free for a minimum of 3 years and not in the pelvis; (for example, carcinoma in situ of the oral cavity is permissible if disease free for a minimum of 3 years; however, patients with prior history of bladder cancer are not allowed no matter the disease free duration); prior hematological (e.g., leukemia, lymphoma, myeloma) malignancy is not allowed * Previous chemotherapy for any other disease site if given within 3 years prior to step 1 * Prior radiotherapy, including brachytherapy, to the region of the study cancer that would result in overlap of radiation therapy treatment volumes * 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 step 1 registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 1 registration * Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C hepatic disease * Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count \< 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count \>= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol * End-stage renal disease (ie, on dialysis or dialysis has been recommended) * Prior allergic reaction to the study drugs involved in this protocol * History of inflammatory bowel disease, prior bowel surgeries (or colostomy) for any reason, or prior partial/radical cystectomy for any reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urinary Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years | Baseline (randomization), 2 years | The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The urinary domain contains 12 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL. |
| Change in Bowel Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years | Baseline, 2 years | The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The bowel domain contains 14 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urinary Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of Radiation Therapy (RT), 6 Months, 1 and 5 Years | Baseline, end of RT, then 6 months,1 and 5 years from the start of RT (5 year time point has not yet been reached). RT dates depend on timing and duration of androgen deprivation therapy (ADT) (optional) and RT. | The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The urinary domain contains 12 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL. |
| Change in Bowel Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of RT, 6 Months, 1 and 5 Years | Baseline, end of RT, then 6 months,1 and 5 years from the start of RT (5 year time point has not yet been reached). RT dates depend on timing and duration of ADT (optional) and RT. | The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The bowel domain contains 14 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL. |
| Percentage of Participants With Biochemical Failure | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. | Biochemical failure was analyzed using two different definitions. The protocol definition of biochemical failure is a PSA measurement ≥ 0.4 ng/mL and rising (i.e. PSA ≥ 0.4 ng/mL followed by a value higher than the first by any amount) or followed by initiation of salvage hormones. The Phoenix definition of biochemical failure is a PSA measurement ≥ PSA nadir + 2 ng/mL where nadir is the lowest post-RT PSA value. Time to biochemical failure is defined as time from randomization to the date of first biochemical failure, last known follow-up (censored), or death without biochemical failure (competing risk). Biochemical failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided. |
| Percentage of Participants With Progression | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. | Progression (failure) is defined as the first occurrence of biochemical failure, local failure, regional failure, distant failure, institution of new unplanned anticancer treatment, or death from prostate cancer. Time to progression is defined as time from randomization to the date of progression, last known follow-up (censored), or death without progression (competing risk). Progression rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided. |
| Percentage of Participants With Local-Regional Failure | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. | Local-regional failure is defined as local or regional failure. Local failure is defined as the development of a new biopsy-proven mass in the prostate bed. Regional failure is defined as radiographic evidence (CT or MRI) of lymphadenopathy (lymph node size ≥ 1.0 cm in the short axis) in a patient without the diagnosis of a hematologic/lymphomatous disorder associated with adenopathy. Time to local-regional failure is defined as time from randomization to the date of first local-regional failure, last known follow-up (censored), or death without local-regional (competing risk). Local-regional failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided. |
| Percentage of Participants Receiving Salvage Therapy | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. | Salvage therapy is defined as the initiation of new unplanned anticancer treatment. Time to salvage therapy initiation is defined as time from randomization to the date of first salvage therapy, last known follow-up (censored), or death without salvage therapy (competing risk). Salvage therapy rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of salvage initiation times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided. |
| Percentage of Participants With Distant Metastasis | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. | Distant metastasis (failure) is defined as radiographic evidence of hematogenous spread evaluated by bone scan, CT, or MRI. Time to distant metastasis is defined as time from randomization to the date of first distant metastasis, last known follow-up (censored), or death without local recurrence (competing risk). Distant metastasis rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided. |
| Percentage of Participants Who Died From Prostate Cancer (Prostate Cancer Specific Mortality) | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. | Cause of death was centrally reviewed. Count and percentage at time of analysis are reported. |
| Percent of Participants Alive (Overall Survival) | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. | Overall survival time is defined as time from registration/randomization to the date of death (failure) from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. 2-year rates are provided. |
| Number of Participants With Grade 3+ Adverse Events | From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly. | Common Terminology Criteria for Adverse Events (CTCAE) version 4 grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. Counts of participants with any grade 3 or higher adverse event, any grade 3 or higher gastrointestinal adverse events, and any grade 3 or higher genitourinary adverse events are reported. Adverse events of any attribution are included. |
Countries
Canada, Switzerland, United States
Contacts
PRINCIPAL_INVESTIGATORMark K Buyyounouski
NRG Oncology
Participant flow
Pre-assignment details
Of 298 screened, 296 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Conventional Radiation Therapy Conventional post-prostatectomy radiation therapy (COPORT) over 7 weeks. Patients may also receive optional androgen deprivation therapy per doctor recommendation.
Conventional radiation therapy: 66.6 Gy in 37 daily fractions of 1.8 Gy to the prostate bed in the absence of disease progression or unacceptable toxicity.
Optional androgen deprivation therapy: Any LHRH agonist/antagonist with or without an oral antiandrogen can be used up to a six-month administration dose, starting 7-9 weeks before radiation therapy and may begin as early as 42 days prior to or any time after screening. An oral antiandrogen alone is not allowed. | 151 |
| Hypofractionated Radiation Therapy Hypofractionated post-prostatectomy radiation therapy (HYPORT) over 5 weeks. Patients may also receive optional androgen deprivation therapy per doctor recommendation.
Hypofractionated radiation therapy: 62.5 Gy in 25 daily fractions of 2.5 Gy to the prostate bed in the absence of disease progression or unacceptable toxicity.
Optional androgen deprivation therapy: Any LHRH agonist/antagonist with or without an oral antiandrogen can be used up to a six-month administration dose, starting 7-9 weeks before radiation therapy and may begin as early as 42 days prior to or any time after screening. An oral antiandrogen alone is not allowed. | 143 |
| Total | 294 |
Baseline characteristics
| Characteristic | Conventional Radiation Therapy | Hypofractionated Radiation Therapy | Total |
|---|---|---|---|
| Age, Customized ≤ 49 years | 3 Participants | 2 Participants | 5 Participants |
| Age, Customized 50 - 59 years | 27 Participants | 31 Participants | 58 Participants |
| Age, Customized 60 - 69 years | 74 Participants | 83 Participants | 157 Participants |
| Age, Customized ≥ 70 years | 47 Participants | 27 Participants | 74 Participants |
| EPIC Group A Score Group (bowel domain score > 96, urinary domain score > 84) | 56 Participants | 52 Participants | 108 Participants |
| EPIC Group B Score Group (bowel domain score > 96, urinary domain score ≤ 84) | 29 Participants | 32 Participants | 61 Participants |
| EPIC Group C Score Group (bowel domain score ≤ 96, urinary domain score > 84) | 31 Participants | 31 Participants | 62 Participants |
| EPIC Group D Score Group (bowel domain score ≤ 96, urinary domain score ≤ 84) | 35 Participants | 28 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 5 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 142 Participants | 136 Participants | 278 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Gleason score 10 | 1 Participants | 1 Participants | 2 Participants |
| Gleason score 6 | 16 Participants | 7 Participants | 23 Participants |
| Gleason score 7 | 105 Participants | 109 Participants | 214 Participants |
| Gleason score 8 | 14 Participants | 15 Participants | 29 Participants |
| Gleason score 9 | 15 Participants | 11 Participants | 26 Participants |
| N-Stage N0 | 121 Participants | 110 Participants | 231 Participants |
| N-Stage NX | 30 Participants | 33 Participants | 63 Participants |
| Prior androgen deprivation therapy (ADT) No | 118 Participants | 110 Participants | 228 Participants |
| Prior androgen deprivation therapy (ADT) Yes | 33 Participants | 33 Participants | 66 Participants |
| Prostate-specific antigen (PSA) ng/mL 0.0 - 0.5 | 135 Participants | 128 Participants | 263 Participants |
| Prostate-specific antigen (PSA) ng/mL 0.6 - 1.0 | 10 Participants | 14 Participants | 24 Participants |
| Prostate-specific antigen (PSA) ng/mL 1.1 - 1.5 | 3 Participants | 1 Participants | 4 Participants |
| Prostate-specific antigen (PSA) ng/mL 1.6 - 2.0 | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 21 Participants | 43 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) White | 125 Participants | 114 Participants | 239 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 151 Participants | 143 Participants | 294 Participants |
| T-Stage T2 | 76 Participants | 60 Participants | 136 Participants |
| T-Stage T3 | 75 Participants | 83 Participants | 158 Participants |
| Zubrod 0 | 128 Participants | 127 Participants | 255 Participants |
| Zubrod 1 | 23 Participants | 16 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 151 | 0 / 143 |
| other Total, other adverse events | 130 / 148 | 120 / 141 |
| serious Total, serious adverse events | 1 / 148 | 8 / 141 |
Outcome results
Primary
Change in Bowel Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years
The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The bowel domain contains 14 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL.
Time frame: Baseline, 2 years
Population: Eligible participants with baseline and two-year data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Conventional Radiation Therapy | Change in Bowel Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years | -1.42 units on a scale | Standard Error 8.35 |
| Hypofractionated Radiation Therapy | Change in Bowel Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years | -4.21 units on a scale | Standard Error 11 |
Comparison: Null hypothesis (H0): mean change score of HYPORT (∆2) is worse than that of COPORT (∆1), specifically ∆2 - ∆1 \< -5. Alternative hypothesis (HA): ∆2 is not worse than ∆1, specifically ∆2 - ∆1 ≥ -5. The study sample size is based on 91% power for this endpoint and 90% power for the urinary endpoint (resulting in 81.9% statistical power to reject the null hypothesis for both endpoints) and a one-sided alpha=0.025 with an overall type I error of 0.05 with a Bonferroni adjustment.p-value: 0.96t-test, 1 sided
Primary
Change in Urinary Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years
The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The urinary domain contains 12 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL.
Time frame: Baseline (randomization), 2 years
Population: Eligible participants with baseline and two-year data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Conventional Radiation Therapy | Change in Urinary Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years | -4.12 units on a scale | Standard Deviation 14.72 |
| Hypofractionated Radiation Therapy | Change in Urinary Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years | -5.06 units on a scale | Standard Deviation 15.16 |
Comparison: Null hypothesis (H0): mean change score of HYPORT (∆2) is worse than that of COPORT (∆1), specifically ∆2 - ∆1 \< -5. Alternative hypothesis (HA): ∆2 is not worse than ∆1, specifically ∆2 - ∆1 ≥ -5. The study sample size is based on 90% power for this endpoint and 91% power for the bowel endpoint (resulting in 81.9% statistical power to reject the null hypothesis for both endpoints) and a one-sided alpha=0.025 with an overall type I error of 0.05 with a Bonferroni adjustment.p-value: 0.98t-test, 1 sided
Secondary
Change in Bowel Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of RT, 6 Months, 1 and 5 Years
The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The bowel domain contains 14 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL.
Time frame: Baseline, end of RT, then 6 months,1 and 5 years from the start of RT (5 year time point has not yet been reached). RT dates depend on timing and duration of ADT (optional) and RT.
Population: Eligible participants with baseline data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Conventional Radiation Therapy | Change in Bowel Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of RT, 6 Months, 1 and 5 Years | End of RT | -6.83 units on a scale | Standard Deviation 15.82 |
| Conventional Radiation Therapy | Change in Bowel Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of RT, 6 Months, 1 and 5 Years | 6 months | -1.90 units on a scale | Standard Deviation 13.63 |
| Conventional Radiation Therapy | Change in Bowel Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of RT, 6 Months, 1 and 5 Years | 1 year | -2.67 units on a scale | Standard Deviation 12.65 |
| Hypofractionated Radiation Therapy | Change in Bowel Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of RT, 6 Months, 1 and 5 Years | 6 months | -2.70 units on a scale | Standard Deviation 13.98 |
| Hypofractionated Radiation Therapy | Change in Bowel Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of RT, 6 Months, 1 and 5 Years | 1 year | -3.11 units on a scale | Standard Deviation 13.93 |
| Hypofractionated Radiation Therapy | Change in Bowel Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of RT, 6 Months, 1 and 5 Years | End of RT | -14.96 units on a scale | Standard Deviation 21.32 |
Comparison: End of RTp-value: 0.0011t-test, 2 sided
Comparison: 6 monthsp-value: 0.93t-test, 2 sided
Comparison: 1 yearp-value: 0.3t-test, 2 sided
Secondary
Change in Urinary Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of Radiation Therapy (RT), 6 Months, 1 and 5 Years
The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The urinary domain contains 12 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL.
Time frame: Baseline, end of RT, then 6 months,1 and 5 years from the start of RT (5 year time point has not yet been reached). RT dates depend on timing and duration of androgen deprivation therapy (ADT) (optional) and RT.
Population: Eligible participants with baseline data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Conventional Radiation Therapy | Change in Urinary Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of Radiation Therapy (RT), 6 Months, 1 and 5 Years | End of RT | -4.34 units on a scale | Standard Deviation 22.61 |
| Conventional Radiation Therapy | Change in Urinary Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of Radiation Therapy (RT), 6 Months, 1 and 5 Years | 6 months | 0.08 units on a scale | Standard Deviation 20.26 |
| Conventional Radiation Therapy | Change in Urinary Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of Radiation Therapy (RT), 6 Months, 1 and 5 Years | 1 year | -2.32 units on a scale | Standard Deviation 22.63 |
| Hypofractionated Radiation Therapy | Change in Urinary Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of Radiation Therapy (RT), 6 Months, 1 and 5 Years | End of RT | -7.90 units on a scale | Standard Deviation 20.93 |
| Hypofractionated Radiation Therapy | Change in Urinary Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of Radiation Therapy (RT), 6 Months, 1 and 5 Years | 6 months | -1.71 units on a scale | Standard Deviation 18.55 |
| Hypofractionated Radiation Therapy | Change in Urinary Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of Radiation Therapy (RT), 6 Months, 1 and 5 Years | 1 year | -5.41 units on a scale | Standard Deviation 21.15 |
Comparison: End of RTp-value: 0.7t-test, 2 sided
Comparison: 6 monthsp-value: 0.67t-test, 2 sided
Comparison: 1 yearp-value: 0.66t-test, 2 sided
Secondary
Number of Participants With Grade 3+ Adverse Events
Common Terminology Criteria for Adverse Events (CTCAE) version 4 grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. Counts of participants with any grade 3 or higher adverse event, any grade 3 or higher gastrointestinal adverse events, and any grade 3 or higher genitourinary adverse events are reported. Adverse events of any attribution are included.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly.
Population: Eligible with adverse event data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Conventional Radiation Therapy | Number of Participants With Grade 3+ Adverse Events | All adverse events | 25 Participants |
| Conventional Radiation Therapy | Number of Participants With Grade 3+ Adverse Events | Gastrointestinal Adverse Events | 3 Participants |
| Conventional Radiation Therapy | Number of Participants With Grade 3+ Adverse Events | Genitourinary Adverse Events | 6 Participants |
| Hypofractionated Radiation Therapy | Number of Participants With Grade 3+ Adverse Events | All adverse events | 20 Participants |
| Hypofractionated Radiation Therapy | Number of Participants With Grade 3+ Adverse Events | Gastrointestinal Adverse Events | 2 Participants |
| Hypofractionated Radiation Therapy | Number of Participants With Grade 3+ Adverse Events | Genitourinary Adverse Events | 10 Participants |
Comparison: Patients with any grade 3 or higher adverse event of any attributionp-value: 0.53Chi-squared
Comparison: Patients with any grade 3 or higher gastrointestinal adverse event of any attributionp-value: 0.6929Chi-squared
Comparison: Patients with any grade 3 or higher genitourinary adverse event of any attributionp-value: 0.2605Chi-squared
Secondary
Percentage of Participants Receiving Salvage Therapy
Salvage therapy is defined as the initiation of new unplanned anticancer treatment. Time to salvage therapy initiation is defined as time from randomization to the date of first salvage therapy, last known follow-up (censored), or death without salvage therapy (competing risk). Salvage therapy rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of salvage initiation times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conventional Radiation Therapy | Percentage of Participants Receiving Salvage Therapy | 7.5 percentage of participants |
| Hypofractionated Radiation Therapy | Percentage of Participants Receiving Salvage Therapy | 5.8 percentage of participants |
p-value: 0.41Gray's test
Secondary
Percentage of Participants Who Died From Prostate Cancer (Prostate Cancer Specific Mortality)
Cause of death was centrally reviewed. Count and percentage at time of analysis are reported.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly.
Population: Eligible participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conventional Radiation Therapy | Percentage of Participants Who Died From Prostate Cancer (Prostate Cancer Specific Mortality) | 0 Participants |
| Hypofractionated Radiation Therapy | Percentage of Participants Who Died From Prostate Cancer (Prostate Cancer Specific Mortality) | 0 Participants |
Secondary
Percentage of Participants With Biochemical Failure
Biochemical failure was analyzed using two different definitions. The protocol definition of biochemical failure is a PSA measurement ≥ 0.4 ng/mL and rising (i.e. PSA ≥ 0.4 ng/mL followed by a value higher than the first by any amount) or followed by initiation of salvage hormones. The Phoenix definition of biochemical failure is a PSA measurement ≥ PSA nadir + 2 ng/mL where nadir is the lowest post-RT PSA value. Time to biochemical failure is defined as time from randomization to the date of first biochemical failure, last known follow-up (censored), or death without biochemical failure (competing risk). Biochemical failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years.
Population: Eligible participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Conventional Radiation Therapy | Percentage of Participants With Biochemical Failure | Protocol definition | 8.3 percentage of participants |
| Conventional Radiation Therapy | Percentage of Participants With Biochemical Failure | Phoenix definition | 3.5 percentage of participants |
| Hypofractionated Radiation Therapy | Percentage of Participants With Biochemical Failure | Protocol definition | 11.8 percentage of participants |
| Hypofractionated Radiation Therapy | Percentage of Participants With Biochemical Failure | Phoenix definition | 8.0 percentage of participants |
Comparison: Protocol definition of biochemical failurep-value: 0.29Gray's test
Comparison: Phoenix definition of biochemical failurep-value: 0.22Gray's test
Secondary
Percentage of Participants With Distant Metastasis
Distant metastasis (failure) is defined as radiographic evidence of hematogenous spread evaluated by bone scan, CT, or MRI. Time to distant metastasis is defined as time from randomization to the date of first distant metastasis, last known follow-up (censored), or death without local recurrence (competing risk). Distant metastasis rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conventional Radiation Therapy | Percentage of Participants With Distant Metastasis | 0.7 percentage of participants |
| Hypofractionated Radiation Therapy | Percentage of Participants With Distant Metastasis | 2.2 percentage of participants |
p-value: 0.6Gray's test
Secondary
Percentage of Participants With Local-Regional Failure
Local-regional failure is defined as local or regional failure. Local failure is defined as the development of a new biopsy-proven mass in the prostate bed. Regional failure is defined as radiographic evidence (CT or MRI) of lymphadenopathy (lymph node size ≥ 1.0 cm in the short axis) in a patient without the diagnosis of a hematologic/lymphomatous disorder associated with adenopathy. Time to local-regional failure is defined as time from randomization to the date of first local-regional failure, last known follow-up (censored), or death without local-regional (competing risk). Local-regional failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conventional Radiation Therapy | Percentage of Participants With Local-Regional Failure | 0.7 percentage of participants |
| Hypofractionated Radiation Therapy | Percentage of Participants With Local-Regional Failure | 0.8 percentage of participants |
p-value: 0.35Gray's test
Secondary
Percentage of Participants With Progression
Progression (failure) is defined as the first occurrence of biochemical failure, local failure, regional failure, distant failure, institution of new unplanned anticancer treatment, or death from prostate cancer. Time to progression is defined as time from randomization to the date of progression, last known follow-up (censored), or death without progression (competing risk). Progression rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year rates are provided.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conventional Radiation Therapy | Percentage of Participants With Progression | 14.4 percentage of participants |
| Hypofractionated Radiation Therapy | Percentage of Participants With Progression | 14.7 percentage of participants |
p-value: 0.96Gray's test
Secondary
Percent of Participants Alive (Overall Survival)
Overall survival time is defined as time from registration/randomization to the date of death (failure) from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. 2-year rates are provided.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conventional Radiation Therapy | Percent of Participants Alive (Overall Survival) | 98.6 percentage of participants |
| Hypofractionated Radiation Therapy | Percent of Participants Alive (Overall Survival) | 98.5 percentage of participants |
p-value: 0.6195% CI: [0.26, 9.47]Log Rank