Prostate Cancer
Conditions
Keywords
adenocarcinoma of the prostate, stage IIB prostate cancer, stage IIA prostate cancer
Brief summary
RATIONALE: Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells and shrink tumors. Androgens can cause the growth of prostate cancer cells. Androgen-deprivation therapy may lessen the amount of androgens made by the body. It is not yet known whether radiation therapy is more effective with or without androgen-deprivation therapy in treating patients with prostate cancer. PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with radiation therapy given together with androgen-deprivation therapy in treating patients with prostate cancer.
Detailed description
OBJECTIVES: Primary * Demonstrate an overall survival (OS) advantage in patients with intermediate-risk prostate cancer treated with dose-escalated radiotherapy (RT) with versus without short-term androgen-deprivation therapy (ADT). Secondary * Determine whether the addition of ADT to dose-escalated RT versus RT alone improves clinical failures, biochemical failure by the "nadir +2", freedom from failure, rate of salvage ADT, and prostate cancer-specific mortality in these patients. * Estimate the magnitude of benefit of ADT with respect to OS in patients treated with different RT modalities (i.e., external-beam radiation therapy alone vs low-dose rate brachytherapy boost vs high-dose rate brachytherapy boost). * Compare acute and late treatment adverse events of these regimens and correlate these events with the presence or absence of pre-existing comorbidity as documented by the Adult Comorbidity Evaluation 27 assessment. OUTLINE: This is a multicenter, dose-escalation study of radiotherapy. Patients are stratified according to number of risk factors (1 vs 2-3), comorbidity (ACE-27 grade ≥ 2 vs \< 2), and radiotherapy (RT) modality (dose-escalated external-beam RT \[EBRT\] vs EBRT and low-dose rate brachytherapy boost vs EBRT and high-dose rate brachytherapy boost). Patients are randomized to 1 of 2 treatment arms. After completion of study therapy, patients are followed up periodically.
Interventions
DRUGbicalutamide
Administered orally at a dose of one 50 mg tablet per day, beginning within (before, same day as, or after) 10 days of the date of the first LHRH agonist (antagonist) therapy administration and continuing for a total duration of 6 months.
DRUGflutamide
Administered orally at a dose of 250 mg (two 125-mg capsules) three times a day for a total daily dose of 750 mg, beginning within (before, same day as, or after) 10 days of with the date of the first LHRH agonist (antagonist) therapy administration and continuing for a total duration of 6 months.
DRUGLHRH agonist (antagonist) therapy
LHRH agonist (antagonist) therapy consists of leuprolide, goserelin, buserelin, triptorelin, or degarelix. The manufacturer's instructions should be followed. The first administration occurs with the start of anti-androgen treatment 8 weeks prior to the start of RT. The total duration of LHRH agonist (antagonist) therapy is 6 months.
RADIATIONDose-Escalated Radiation Therapy
External beam radiotherapy (EBRT) as 3D Conformal Radiotherapy (3DCRT) or intensity-modulated radiation therapy (IMRT). Brachytherapy is optional, at the discretion of the treating physician. Patients treated entirely via EBRT receive 79.2 Gy delivered in 1.8 Gy fractions. Patients who receive brachytherapy as a component of their RT receive 45 Gy EBRT in 1.8 Gy fractions. Low-dose brachytherapy boost occurs following the EBRT portion of treatment no more than 4 weeks following its completion.High-dose rate brachytherapy boost is delivered in 2 fractions separated by a minimum time span of 6 hours and the implant(s) may be performed during the EBRT portion of the treatment or within 1 week prior to its initiation or following its completion.
Sponsors
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
NRG Oncology
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
1. Pathologically (histologically) proven diagnosis of prostatic adenocarcinoma, at intermediate risk for recurrence, within 180 days prior to registration as determined by having one or more of the following intermediate-risk features: Gleason score 7; prostate-specific antigen (PSA) \>10 but ≤20; clinical stage T2b-T2c. * Patients previously diagnosed with low risk (Gleason score ≤ 6, clinical stage \< T2a, and PSA \< 10) prostate cancer undergoing active surveillance who are re-biopsied and found to have intermediate risk disease according to the protocol criteria are eligible for enrollment within 180 days of the repeat biopsy procedure. 2. Clinically negative lymph nodes as established by imaging (pelvic +/- abdominal CT or MRI), nodal sampling, or dissection within 60 days prior to registration, except as noted immediately below: * Patients with a single intermediate risk factor only do not require abdominopelvic imaging, but these studies may be obtained at the discretion of the treating physician. Patients with 2 or 3 risk factors are required to undergo pelvic +/- abdominal CT or MRI. * Patients with lymph nodes equivocal or questionable by imaging are eligible without biopsy if the nodes are ≤1.5 cm; any node larger than this on imaging will require negative biopsy for eligibility. 3. No evidence of bone metastases (M0) on bone scan within 60 days prior to registration. * Bone scan is not required for patients enrolled with a single intermediate risk factor only, but this scan may be obtained at the discretion of the treating physician. Patients with 2 or 3 risk factors will require a negative bone scan for eligibility. * Equivocal bone scan findings are allowed if plain film x-rays are negative for metastasis. 4. History/physical examination (to include, at a minimum, digital rectal examination of the prostate and examination of the skeletal system and abdomen, and formal comorbidity assessment via the ACE-27 instrument) within 60 days prior to registration. 5. Zubrod Performance Status 0-1 6. Age ≥ 18 7. Baseline serum PSA value performed with an FDA-approved assay (e.g., Abbott, Hybritech) within 60 days prior to registration * Study entry PSA must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of ADT; (3) within 30 days after discontinuation of finasteride; or (4) within 90 days after discontinuation of dutasteride. 8. For patients undergoing brachytherapy only: complete blood count (CBC)/differential obtained within 60 days prior to registration, with adequate bone marrow function defined as follows: * Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3 * Platelets ≥ 100,000 cells/mm3 * Hemoglobin (Hgb) ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.) 9. Patient must be able to provide study-specific informed consent prior to study entry.
Exclusion criteria
1. Patients with Gleason Score ≥ 8; PSA \> 20; OR Clinical Stage ≥ T3 are ineligible for this trial. * Should findings of extracapsular extension or seminal vesicle invasion be noted on prostate MRI, this study, if used, will not render patients ineligible for accrual to this protocol. Primary tumor staging for eligibility purposes is to be based on palpable or core biopsy evidence only with respect to extracapsular extension or seminal vesicle involvement. 2. Patients with all three intermediate risk factors who also have ≥ 50% of the number of their biopsy cores positive for cancer are ineligible for this trial. 3. Prior invasive malignancy (except non-melanomatous skin cancer) or hematological (e.g., leukemia, lymphoma, myeloma) malignancy unless disease free for a minimum of 5 years (prior diagnoses of carcinoma in situ are permitted) 4. Prior radical surgery (prostatectomy), high-intensity focused ultrasound (HIFU) or cryosurgery for prostate cancer 5. Prior hormonal therapy, such as LHRH agonists (e.g., goserelin, leuprolide), antiandrogens (e.g., flutamide, bicalutamide), estrogens (e.g., DES), or bilateral orchiectomy 6. Use of finasteride within 30 days prior to registration 7. Use of dutasteride within 90 days prior to registration 8. Prior or concurrent cytotoxic chemotherapy for prostate cancer; prior chemotherapy for a different cancer is permitted. 9. Prior RT, including brachytherapy, to the region of the study cancer that would result in overlap of RT fields * Any patient undergoing brachytherapy must have transrectal ultrasound confirmation of prostate volume \<60 cc, American Urological Association Symptom Index (AUA-SI) score ≤15 within 60 days of registration, and no history of prior transurethral resection of the prostate (TURP); prior TURP is permitted for patients who receive EBRT only) 10. 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 within 30 days before registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol. * Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. While the treatment employed in this study is not significantly immunosuppressive, it is felt that a diagnosis of AIDS associated with prostate cancer is likely to impact this study's primary endpoint of overall survival. Patients who are HIV seropositive but do not meet criteria for diagnosis of AIDS are eligible for study participation. 11. Men who are sexually active with a woman of child-bearing potential and not willing/able to use medically acceptable forms of contraception (e.g., surgical, barrier, medicinal) during protocol treatment and during the first 3 months after cessation of protocol treatment; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Alive (Overall Survival) | From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here. | Overall survival time is defined as time from randomization to the date of death 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Biochemical Failure | From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here. | Biochemical failure is defined as an increase of at least 2 ng/ml above the nadir PSA. Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported. |
| Percentage of Participants With Local Recurrence | From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here. | Local recurrence (failure) is defined as clinical (palpable) suspicion of local recurrence \[this date is used\] confirmed by biopsy. Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported. |
| Percentage of Participants With Regional Recurrence | From randomization to last follow-up. Maximum follow-up at time of analysis was 10.3 years. | Regional recurrence is defined as the documented progression in pelvic lymph nodes. If discovered on image of the pelvis prompted by a biochemical failure, then the event date would be the date of documented biochemical failure. |
| Percentage of Participants With Distant Metastasis | From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here. | Distant metastasis (failure) is defined as metastatic disease documented by any method. If diagnosed on diagnostic imaging prompted by biochemical failure, then the event date will be the date of biochemical progression. Failure time is defined as time from randomization to the date of first failure, last known follow-up (competing risk), or death without failure (censored). 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported. |
| Percentage of Participants Dead Due to Prostate Cancer (Prostate Cancer-specific Mortality) | From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here. | Prostate cancer specific mortality (failure) is defined as death due to prostate cancer or a complication from treatment. Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported. |
| Percentage of Participants Dead Due to Cause Other Than Prostate Cancer (Non-Prostate Cancer-specific Mortality) | From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here. | Non-prostate cancer specific mortality is defined as a death without evidence of prostate cancer or a complication from treatment. . Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported. |
| Percentage of Participants Receiving Salvage Androgen Deprivation Therapy (ADT) | From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here. | Salvage (non-protocol) ADT administration is defined as the first administration of subsequent ADT (either LHRH agonist or anti-androgen) Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). Salvage ADT rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of salvage ADT times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported. |
| Percentage of Participants Alive (Overall Survival) by Radiation Therapy Modality | From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here. | Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported. |
| Number of Participants With Acute Adverse Events | From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. | Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. Acute adverse events are defined as occuring within 30 days of completion of radiation therapy. |
| Percentage of Participants With Late Grade 3+ Adverse Events | From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates are reported here. | Common Terminology Criteria for Adverse Events (version 4.0) 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. Late adverse events are defined as occurring more than 30 days after the end of radiation therapy. Failure is defined as grade 3 or higher late adverse event. Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported. |
| Percentage of Participants Failed (Freedom From Failure) | From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates are reported here. | Failure is defined as biochemical failure, local failure, or distant metastasis. Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported. |
| Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Urinary Domain Score | Last week of RT (approximately 9 and 17 weeks from start of protocol treatment for Arm 1 and 2, respectively), then 6 months, 1 year and 5 years from end of RT. | The EPIC assesses disease-specific aspects of prostate cancer and it's therapies and consists of four summary domains (bowel, urinary, sexual, and hormonal), each ranging from 0-100, with higher scores representing better health-related quality of life. Change is calculated as time point value - baseline value, such that a positive change indicates improvement. |
| Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain Score | Last week of RT (approximately 9 and 17 weeks from start of protocol treatment for Arm 1 and 2, respectively), then 6 months, 1 year and 5 years from end of RT. | The EPIC assesses disease-specific aspects of prostate cancer and it's therapies and consists of four summary domains (bowel, urinary, sexual, and hormonal), each ranging from 0-100, with higher scores representing better health-related quality of life. Change is calculated as time point value - baseline value, such that a positive change indicates improvement. |
| Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Hormonal Domain Score | Last week of RT (approximately 9 and 17 weeks from start of protocol treatment for Arm 1 and 2, respectively), then 6 months, 1 year and 5 years from end of RT. | The EPIC assesses disease-specific aspects of prostate cancer and it's therapies and consists of four summary domains (bowel, urinary, sexual, and hormonal), each ranging from 0-100, with higher scores representing better health-related quality of life. Change is calculated as time point value - baseline value, such that a positive change indicates improvement. |
| Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Score | Last week of RT (approximately 9 and 17 weeks from start of protocol treatment for Arm 1 and 2, respectively), then 6 months, 1 year and 5 years from end of RT. | The EPIC assesses disease-specific aspects of prostate cancer and it's therapies and consists of four summary domains (bowel, urinary, sexual, and hormonal), each ranging from 0-100, with higher scores representing better health-related quality of life. Change is calculated as time point value - baseline value, such that a positive change indicates improvement. |
| Change From Baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Domain Score | Last week of RT (approximately 9 and 17 weeks from start of protocol treatment for Arm 1 and 2, respectively), then 6 months, 1 year and 5 years from end of RT. | The PROMIS Fatigue short form 8a contains 8 questions, each with 5 responses ranging from 1 to 5, evaluating self-reported fatigue symptoms over the past 7 days. The total score is the sum of all questions which is then converted into a pro-rated T-score with a mean of 50 and standard deviation of 10, with a possible range of 33.1 to 77.8. Higher scores indicate more fatigue. Change is defined as value at one year - value at baseline. Positive change from baseline indicates increased fatigue at one year. |
| Quality Adjusted Life Years (QALYs) | Last week of RT (approximately 9 and 17 weeks from start of protocol treatment for Arm 1 and 2, respectively), then 6 months, 1 year and 5 years from end of RT. | — |
| Correlation Between PROMIS Fatigue Score Change and Plasma Cytokine Change | From date of randomization to 3 weeks from start of RT. | — |
Countries
Canada, United States
Contacts
STUDY_CHAIRAlvaro A. Martinez, MD, FACR
21st Century Oncology - Michigan Institute for Radiation Oncology
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose-Escalated Radiation Therapy Alone Radiation therapy consists of 79.2 Gy EBRT only or 45 Gy EBRT followed by low- or high-dose rate brachytherapy. EBRT is delivered in 1.8 Gy daily fractions. | 750 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation Radiation therapy consists of 79.2 Gy EBRT only or 45 Gy EBRT followed by low- or high-dose rate brachytherapy. EBRT is delivered in 1.8 Gy daily fractions.
Six months of androgen-deprivation therapy starts 8 weeks prior to start of radiation therapy and consists of LHRH agonist (antagonist) therapy (leuprolide, goserelin, buserelin. triptorelin, or degarelix) and anti-androgen therapy (bicalutamide or flutamide). | 742 |
| Total | 1,492 |
Baseline characteristics
| Characteristic | Dose-Escalated Radiation Therapy Alone | Total | Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation |
|---|---|---|---|
| Age, Customized Age ≤ 49 years | 9 Participants | 19 Participants | 10 Participants |
| Age, Customized Age 50-59 years | 105 Participants | 201 Participants | 96 Participants |
| Age, Customized Age 60 - 69 years | 361 Participants | 681 Participants | 320 Participants |
| Age, Customized Age ≥ 70 years | 275 Participants | 591 Participants | 316 Participants |
| Comorbidity Status [Adult Comorbidity Evaluation 27 (ACE-27) ] ACE-27 < grade 2 | 246 Participants | 492 Participants | 246 Participants |
| Comorbidity Status [Adult Comorbidity Evaluation 27 (ACE-27) ] ACE-27 ≥ grade 2 | 504 Participants | 1000 Participants | 496 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 41 Participants | 78 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 681 Participants | 1363 Participants | 682 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 28 Participants | 51 Participants | 23 Participants |
| Gleason Score 2-6 | 64 Participants | 123 Participants | 59 Participants |
| Gleason Score 7 | 686 Participants | 1369 Participants | 683 Participants |
| M-Stage M0 | 657 Participants | 1323 Participants | 666 Participants |
| M-Stage M1 | 2 Participants | 2 Participants | 0 Participants |
| M-Stage MX | 91 Participants | 167 Participants | 76 Participants |
| N-Stage N0 | 611 Participants | 1215 Participants | 604 Participants |
| N-Stage N1 | 3 Participants | 7 Participants | 4 Participants |
| N-Stage NX | 136 Participants | 270 Participants | 134 Participants |
| Number of risk factors One | 504 Participants | 994 Participants | 490 Participants |
| Number of risk factors Two or three | 246 Participants | 498 Participants | 252 Participants |
| Prostate-Specific Antigen (PSA) ng/mL <10 | 538 Participants | 1068 Participants | 530 Participants |
| Prostate-Specific Antigen (PSA) ng/mL 10-20 | 212 Participants | 424 Participants | 212 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 18 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 158 Participants | 314 Participants | 156 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 18 Participants | 36 Participants | 18 Participants |
| Race (NIH/OMB) White | 557 Participants | 1111 Participants | 554 Participants |
| Radiation Therapy Modality Dose-escalated EBRT | 665 Participants | 1321 Participants | 656 Participants |
| Radiation Therapy Modality EBRT + HDR brachytherapy boost | 12 Participants | 23 Participants | 11 Participants |
| Radiation Therapy Modality EBRT + LDR brachytherapy boost | 73 Participants | 148 Participants | 75 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 750 Participants | 1492 Participants | 742 Participants |
| T-Stage T1 | 493 Participants | 942 Participants | 449 Participants |
| T-Stage T2 | 257 Participants | 550 Participants | 293 Participants |
| Zubrod Performance Status 0 | 642 Participants | 1287 Participants | 645 Participants |
| Zubrod Performance Status 1 | 108 Participants | 204 Participants | 96 Participants |
| Zubrod Performance Status Missing | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 119 / 750 | 100 / 742 |
| other Total, other adverse events | 597 / 733 | 647 / 725 |
| serious Total, serious adverse events | 20 / 733 | 33 / 725 |
Outcome results
Primary
Percentage of Participants Alive (Overall Survival)
Overall survival time is defined as time from randomization to the date of death 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported.
Time frame: From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Percentage of Participants Alive (Overall Survival) | 90.0 percentage of participants |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Percentage of Participants Alive (Overall Survival) | 91.0 percentage of participants |
Comparison: This study was designed to detect an improvement in the 5-year overall survival rate from 90% (radiation alone arm) to 93.3% (radiation and androgen deprivation arm). Assuming an exponential survival distribution for each arm, this translates to a 34% relative reduction (hazard ratio 0.66) in the yearly death rate. At least 218 deaths provide 85% power with a 1-sided significance level of 0.025 and 85% power.p-value: 0.2295% CI: [0.65, 1.11]Log Rank
Secondary
Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain Score
The EPIC assesses disease-specific aspects of prostate cancer and it's therapies and consists of four summary domains (bowel, urinary, sexual, and hormonal), each ranging from 0-100, with higher scores representing better health-related quality of life. Change is calculated as time point value - baseline value, such that a positive change indicates improvement.
Time frame: Last week of RT (approximately 9 and 17 weeks from start of protocol treatment for Arm 1 and 2, respectively), then 6 months, 1 year and 5 years from end of RT.
Population: Eligible participants who consented to quality of life component and have data at baseline and time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain Score | End of RT | -9.7 score on a scale | Standard Deviation 14.7 |
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain Score | Six months post-RT | -2.6 score on a scale | Standard Deviation 12.8 |
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain Score | One year post-RT | -4.0 score on a scale | Standard Deviation 12.8 |
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain Score | Five years post-RT | -2.7 score on a scale | Standard Deviation 13.2 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain Score | Five years post-RT | -2.9 score on a scale | Standard Deviation 10.7 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain Score | End of RT | -10.5 score on a scale | Standard Deviation 13.7 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain Score | One year post-RT | -5.2 score on a scale | Standard Deviation 13.4 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain Score | Six months post-RT | -3.8 score on a scale | Standard Deviation 9.6 |
Comparison: End of RTp-value: 0.58t-test, 2 sided
Comparison: Six months post-RTp-value: 0.31t-test, 2 sided
Comparison: One year post-RTp-value: 0.36t-test, 2 sided
Comparison: Five years post-RTp-value: 0.88t-test, 2 sided
Secondary
Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Hormonal Domain Score
The EPIC assesses disease-specific aspects of prostate cancer and it's therapies and consists of four summary domains (bowel, urinary, sexual, and hormonal), each ranging from 0-100, with higher scores representing better health-related quality of life. Change is calculated as time point value - baseline value, such that a positive change indicates improvement.
Time frame: Last week of RT (approximately 9 and 17 weeks from start of protocol treatment for Arm 1 and 2, respectively), then 6 months, 1 year and 5 years from end of RT.
Population: Eligible participants who consented to quality of life component and have data at baseline and time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Hormonal Domain Score | One year post-RT | -0.8 score on a scale | Standard Deviation 14.7 |
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Hormonal Domain Score | End of RT | -1.8 score on a scale | Standard Deviation 10.2 |
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Hormonal Domain Score | Six months post-RT | -0.7 score on a scale | Standard Deviation 11.9 |
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Hormonal Domain Score | Five years post-RT | -0.3 score on a scale | Standard Deviation 15.9 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Hormonal Domain Score | Five years post-RT | -2.7 score on a scale | Standard Deviation 13.9 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Hormonal Domain Score | One year post-RT | -7.8 score on a scale | Standard Deviation 14.4 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Hormonal Domain Score | Six months post-RT | -13.7 score on a scale | Standard Deviation 16.9 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Hormonal Domain Score | End of RT | -18.4 score on a scale | Standard Deviation 16.2 |
Comparison: End of RTp-value: <0.001t-test, 2 sided
Comparison: Six months post-RTp-value: <0.001t-test, 2 sided
Comparison: One year post-RTp-value: <0.001t-test, 2 sided
Comparison: Five years post-RTp-value: 0.18t-test, 2 sided
Secondary
Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Score
The EPIC assesses disease-specific aspects of prostate cancer and it's therapies and consists of four summary domains (bowel, urinary, sexual, and hormonal), each ranging from 0-100, with higher scores representing better health-related quality of life. Change is calculated as time point value - baseline value, such that a positive change indicates improvement.
Time frame: Last week of RT (approximately 9 and 17 weeks from start of protocol treatment for Arm 1 and 2, respectively), then 6 months, 1 year and 5 years from end of RT.
Population: Eligible participants who consented to quality of life component and have data at baseline and time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Score | End of RT | -6.7 score on a scale | Standard Deviation 18.9 |
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Score | Six months post-RT | -7.9 score on a scale | Standard Deviation 23 |
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Score | One year post-RT | -8.5 score on a scale | Standard Deviation 22.7 |
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Score | Five years post-RT | -10.0 score on a scale | Standard Deviation 26.6 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Score | Five years post-RT | -9.6 score on a scale | Standard Deviation 27.6 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Score | End of RT | -22.6 score on a scale | Standard Deviation 25.8 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Score | One year post-RT | -16.6 score on a scale | Standard Deviation 23.7 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Score | Six months post-RT | -19.9 score on a scale | Standard Deviation 25.3 |
Comparison: End of RTp-value: <0.001t-test, 2 sided
Comparison: Six months post-RTp-value: <0.001t-test, 2 sided
Comparison: One year post-RTp-value: 0.0014t-test, 2 sided
Comparison: Five years post-RTp-value: 0.9t-test, 2 sided
Secondary
Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Urinary Domain Score
The EPIC assesses disease-specific aspects of prostate cancer and it's therapies and consists of four summary domains (bowel, urinary, sexual, and hormonal), each ranging from 0-100, with higher scores representing better health-related quality of life. Change is calculated as time point value - baseline value, such that a positive change indicates improvement.
Time frame: Last week of RT (approximately 9 and 17 weeks from start of protocol treatment for Arm 1 and 2, respectively), then 6 months, 1 year and 5 years from end of RT.
Population: Eligible participants who consented to quality of life component and have data at baseline and time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Urinary Domain Score | End of RT | -12.4 score on a scale | Standard Deviation 17 |
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Urinary Domain Score | Six months post-RT | -0.1 score on a scale | Standard Deviation 14.9 |
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Urinary Domain Score | One year post-RT | -1.9 score on a scale | Standard Deviation 15.9 |
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Urinary Domain Score | Five years post-RT | -0.4 score on a scale | Standard Deviation 14.9 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Urinary Domain Score | Five years post-RT | 0.3 score on a scale | Standard Deviation 12.3 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Urinary Domain Score | End of RT | -13.8 score on a scale | Standard Deviation 15.4 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Urinary Domain Score | One year post-RT | -1.6 score on a scale | Standard Deviation 15.3 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Urinary Domain Score | Six months post-RT | -3.6 score on a scale | Standard Deviation 15.3 |
Comparison: End of RTp-value: 0.38t-test, 2 sided
Comparison: 6 months post-RTp-value: 0.032t-test, 2 sided
Comparison: One year post-RTp-value: 0.87t-test, 2 sided
Comparison: Five years post-RTp-value: 0.67t-test, 2 sided
Secondary
Change From Baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Domain Score
The PROMIS Fatigue short form 8a contains 8 questions, each with 5 responses ranging from 1 to 5, evaluating self-reported fatigue symptoms over the past 7 days. The total score is the sum of all questions which is then converted into a pro-rated T-score with a mean of 50 and standard deviation of 10, with a possible range of 33.1 to 77.8. Higher scores indicate more fatigue. Change is defined as value at one year - value at baseline. Positive change from baseline indicates increased fatigue at one year.
Time frame: Last week of RT (approximately 9 and 17 weeks from start of protocol treatment for Arm 1 and 2, respectively), then 6 months, 1 year and 5 years from end of RT.
Population: Participants who consented to QOL component and have data at baseline and timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Domain Score | End of RT | 0.80 score on a scale | Standard Deviation 4.66 |
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Domain Score | Six months post-RT | 1.09 score on a scale | Standard Deviation 5.14 |
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Domain Score | One year post_RT | 0.99 score on a scale | Standard Deviation 6 |
| Dose-Escalated Radiation Therapy Alone | Change From Baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Domain Score | Five years post-RT | 0.97 score on a scale | Standard Deviation 6.71 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Domain Score | Five years post-RT | 0.80 score on a scale | Standard Deviation 5.62 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Domain Score | End of RT | 1.84 score on a scale | Standard Deviation 5.54 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Domain Score | One year post_RT | 0.86 score on a scale | Standard Deviation 5.08 |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Change From Baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Domain Score | Six months post-RT | 1.21 score on a scale | Standard Deviation 5.34 |
Comparison: End of RTp-value: 0.046t-test, 2 sided
Comparison: 6 months post-RTp-value: 0.82t-test, 2 sided
Comparison: One year post-RTp-value: 0.82t-test, 2 sided
Comparison: Five years post-RTp-value: 0.79t-test, 2 sided
Secondary
Correlation Between PROMIS Fatigue Score Change and Plasma Cytokine Change
Time frame: From date of randomization to 3 weeks from start of RT.
Population: The protocol did not provide sufficient detail to meet current National Cancer Institute requirements for release of specimens from the NRG Oncology tissue bank for the protocol-specified analysis, therefore no assays were performed, and no data were collected for this outcome measure (cytokine levels). Specimen use will require future federal approval and funding separate from this trial.
Secondary
Number of Participants With Acute Adverse Events
Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. Acute adverse events are defined as occuring within 30 days of completion of radiation therapy.
Time frame: From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years.
Population: Eligible participants who started protocol treatment and have adverse event data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Number of Participants With Acute Adverse Events | 152 Participants |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Number of Participants With Acute Adverse Events | 504 Participants |
p-value: <0.001t-test, 2 sided
Secondary
Percentage of Participants Alive (Overall Survival) by Radiation Therapy Modality
Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported.
Time frame: From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here.
Population: Eligible participants with radiation treatment data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Percentage of Participants Alive (Overall Survival) by Radiation Therapy Modality | EBRT | 89.4 percentage of participants |
| Dose-Escalated Radiation Therapy Alone | Percentage of Participants Alive (Overall Survival) by Radiation Therapy Modality | EBRT +LDR Brachytherapy Boost | 100 percentage of participants |
| Dose-Escalated Radiation Therapy Alone | Percentage of Participants Alive (Overall Survival) by Radiation Therapy Modality | EBRT +HDR Brachytherapy Boost | 91.7 percentage of participants |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Percentage of Participants Alive (Overall Survival) by Radiation Therapy Modality | EBRT | 90.3 percentage of participants |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Percentage of Participants Alive (Overall Survival) by Radiation Therapy Modality | EBRT +LDR Brachytherapy Boost | 97.2 percentage of participants |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Percentage of Participants Alive (Overall Survival) by Radiation Therapy Modality | EBRT +HDR Brachytherapy Boost | 100 percentage of participants |
Secondary
Percentage of Participants Dead Due to Cause Other Than Prostate Cancer (Non-Prostate Cancer-specific Mortality)
Non-prostate cancer specific mortality is defined as a death without evidence of prostate cancer or a complication from treatment. . Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported.
Time frame: From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Percentage of Participants Dead Due to Cause Other Than Prostate Cancer (Non-Prostate Cancer-specific Mortality) | 9.1 percentage of participants |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Percentage of Participants Dead Due to Cause Other Than Prostate Cancer (Non-Prostate Cancer-specific Mortality) | 9.0 percentage of participants |
Comparison: Cause-specific hazard modelp-value: 0.5295% CI: [0.7, 1.2]Log Rank
Comparison: Cumulative incidence modelp-value: 0.56Gray's test
Secondary
Percentage of Participants Dead Due to Prostate Cancer (Prostate Cancer-specific Mortality)
Prostate cancer specific mortality (failure) is defined as death due to prostate cancer or a complication from treatment. Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported.
Time frame: From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Percentage of Participants Dead Due to Prostate Cancer (Prostate Cancer-specific Mortality) | 0.90 percentage of participants |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Percentage of Participants Dead Due to Prostate Cancer (Prostate Cancer-specific Mortality) | 0 percentage of participants |
Comparison: Cause-specific hazard modelp-value: 0.007395% CI: [0.01, 0.8]Log Rank
Comparison: Cumulative incidence modelp-value: 0.007Gray's test
Secondary
Percentage of Participants Failed (Freedom From Failure)
Failure is defined as biochemical failure, local failure, or distant metastasis. Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported.
Time frame: From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates are reported here.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Percentage of Participants Failed (Freedom From Failure) | 14.8 percentage of participants |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Percentage of Participants Failed (Freedom From Failure) | 7.9 percentage of participants |
Comparison: Cause-specific hazard modelp-value: <0.00195% CI: [0.39, 0.7]Log Rank
Comparison: Cumulative incidence modelp-value: <0.001Gray's test
Secondary
Percentage of Participants Receiving Salvage Androgen Deprivation Therapy (ADT)
Salvage (non-protocol) ADT administration is defined as the first administration of subsequent ADT (either LHRH agonist or anti-androgen) Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). Salvage ADT rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of salvage ADT times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported.
Time frame: From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Percentage of Participants Receiving Salvage Androgen Deprivation Therapy (ADT) | 6.1 percentage of participants |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Percentage of Participants Receiving Salvage Androgen Deprivation Therapy (ADT) | 4.2 percentage of participants |
Comparison: Cause-specific hazard modelp-value: 0.02595% CI: [0.41, 0.95]Log Rank
Comparison: Cumulative incidence modelp-value: 0.025Gray's test
Secondary
Percentage of Participants With Biochemical Failure
Biochemical failure is defined as an increase of at least 2 ng/ml above the nadir PSA. Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported.
Time frame: From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Percentage of Participants With Biochemical Failure | 13.9 percentage of participants |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Percentage of Participants With Biochemical Failure | 7.7 percentage of participants |
Comparison: Cause-specific hazard modelp-value: <0.00195% CI: [0.39, 0.7]Log Rank
Comparison: Cumulative incidence modelp-value: <0.001Gray's test
Secondary
Percentage of Participants With Distant Metastasis
Distant metastasis (failure) is defined as metastatic disease documented by any method. If diagnosed on diagnostic imaging prompted by biochemical failure, then the event date will be the date of biochemical progression. Failure time is defined as time from randomization to the date of first failure, last known follow-up (competing risk), or death without failure (censored). 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported.
Time frame: From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Percentage of Participants With Distant Metastasis | 3.1 percentage of participants |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Percentage of Participants With Distant Metastasis | 0.6 percentage of participants |
Comparison: Cause-specific hazard modelp-value: <0.00195% CI: [0.11, 0.57]Log Rank
Comparison: Cumulative incidence modelp-value: <0.001Gray's test
Secondary
Percentage of Participants With Late Grade 3+ Adverse Events
Common Terminology Criteria for Adverse Events (version 4.0) 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. Late adverse events are defined as occurring more than 30 days after the end of radiation therapy. Failure is defined as grade 3 or higher late adverse event. Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported.
Time frame: From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates are reported here.
Population: Eligible participants who started protocol treatment and have adverse event data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Percentage of Participants With Late Grade 3+ Adverse Events | 12.8 percentage of participants |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Percentage of Participants With Late Grade 3+ Adverse Events | 15.2 percentage of participants |
p-value: 0.1395% CI: [0.89, 1.53]Gray's test
Secondary
Percentage of Participants With Local Recurrence
Local recurrence (failure) is defined as clinical (palpable) suspicion of local recurrence \[this date is used\] confirmed by biopsy. Failure time is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). 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. Five-year rates are provided here. Analysis was planned to occur after 218 deaths were reported.
Time frame: From randomization to last follow-up. Follow-up schedule: end of RT (2nd arm only), then every 3 months for a year, every 4 months for 4 years, then yearly. Maximum follow-up at time of analysis was 10.3 years. Five-year rates reported here.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-Escalated Radiation Therapy Alone | Percentage of Participants With Local Recurrence | 2.6 percentage of participants |
| Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation | Percentage of Participants With Local Recurrence | 0.6 percentage of participants |
Comparison: Cause-specific hazard modelp-value: 0.0295% CI: [0.22, 0.9]Log Rank
p-value: 0.021Gray's test
Secondary
Percentage of Participants With Regional Recurrence
Regional recurrence is defined as the documented progression in pelvic lymph nodes. If discovered on image of the pelvis prompted by a biochemical failure, then the event date would be the date of documented biochemical failure.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 10.3 years.
Population: Regional recurrence data was not collected and therefore cannot be reported.
Secondary
Quality Adjusted Life Years (QALYs)
Time frame: Last week of RT (approximately 9 and 17 weeks from start of protocol treatment for Arm 1 and 2, respectively), then 6 months, 1 year and 5 years from end of RT.
Population: The protocol states that this outcome measure will be analyzed only if the primary endpoint hypothesis is substantiated, which it was not. Therefore no patients were analyzed.