Trial Outcomes & Findings for Radiation Therapy With or Without Androgen-Deprivation Therapy in Treating Patients With Prostate Cancer (NCT NCT00936390)

Last Updated: 2025-10-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1538 participants

Primary outcome timeframe

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.

Results posted on

2025-10-15

Participant Flow

Participant milestones

Participant milestones
Measure	Dose-Escalated Radiation Therapy Alone Radiation therapy consists of 79.2 Gy external beam radiotherapy (EBRT) only or 45 Gy EBRT followed by low dose rate (LDR) or high-dose rate (HDR) brachytherapy. EBRT is delivered in 1.8 Gy daily fractions.	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 luteinizing-hormone releasing-hormone (LHRH) agonist (antagonist) therapy (leuprolide, goserelin, buserelin. triptorelin, or degarelix) and anti-androgen therapy (bicalutamide or flutamide).
Overall Study STARTED	771	767
Overall Study Eligible	750	742
Overall Study Eligible, Started Protocol Treatment, Has Adverse Event Data	733	725
Overall Study Eligible With Radiation Treatment Data	725	707
Overall Study Eligible and Consented to Quality of Life Component	215	205
Overall Study COMPLETED	750	742
Overall Study NOT COMPLETED	21	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose-Escalated Radiation Therapy Alone Radiation therapy consists of 79.2 Gy external beam radiotherapy (EBRT) only or 45 Gy EBRT followed by low dose rate (LDR) or high-dose rate (HDR) brachytherapy. EBRT is delivered in 1.8 Gy daily fractions.	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 luteinizing-hormone releasing-hormone (LHRH) agonist (antagonist) therapy (leuprolide, goserelin, buserelin. triptorelin, or degarelix) and anti-androgen therapy (bicalutamide or flutamide).
Overall Study Protocol Violation	21	25

Baseline Characteristics

Radiation Therapy With or Without Androgen-Deprivation Therapy in Treating Patients With Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose-Escalated Radiation Therapy Alone n=750 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=742 Participants 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).	Total n=1492 Participants Total of all reporting groups
Age, Customized Age · ≤ 49 years	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Age, Customized Age · 50-59 years	105 Participants n=5 Participants	96 Participants n=7 Participants	201 Participants n=5 Participants
Age, Customized Age · 60 - 69 years	361 Participants n=5 Participants	320 Participants n=7 Participants	681 Participants n=5 Participants
Age, Customized Age · ≥ 70 years	275 Participants n=5 Participants	316 Participants n=7 Participants	591 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	750 Participants n=5 Participants	742 Participants n=7 Participants	1492 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	41 Participants n=5 Participants	37 Participants n=7 Participants	78 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	681 Participants n=5 Participants	682 Participants n=7 Participants	1363 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	28 Participants n=5 Participants	23 Participants n=7 Participants	51 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Asian	11 Participants n=5 Participants	7 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	158 Participants n=5 Participants	156 Participants n=7 Participants	314 Participants n=5 Participants
Race (NIH/OMB) White	557 Participants n=5 Participants	554 Participants n=7 Participants	1111 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Zubrod Performance Status 0	642 Participants n=5 Participants	645 Participants n=7 Participants	1287 Participants n=5 Participants
Zubrod Performance Status 1	108 Participants n=5 Participants	96 Participants n=7 Participants	204 Participants n=5 Participants
Zubrod Performance Status Missing	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Number of risk factors One	504 Participants n=5 Participants	490 Participants n=7 Participants	994 Participants n=5 Participants
Number of risk factors Two or three	246 Participants n=5 Participants	252 Participants n=7 Participants	498 Participants n=5 Participants
Comorbidity Status [Adult Comorbidity Evaluation 27 (ACE-27) ] ACE-27 < grade 2	246 Participants n=5 Participants	246 Participants n=7 Participants	492 Participants n=5 Participants
Comorbidity Status [Adult Comorbidity Evaluation 27 (ACE-27) ] ACE-27 ≥ grade 2	504 Participants n=5 Participants	496 Participants n=7 Participants	1000 Participants n=5 Participants
Radiation Therapy Modality Dose-escalated EBRT	665 Participants n=5 Participants	656 Participants n=7 Participants	1321 Participants n=5 Participants
Radiation Therapy Modality EBRT + LDR brachytherapy boost	73 Participants n=5 Participants	75 Participants n=7 Participants	148 Participants n=5 Participants
Radiation Therapy Modality EBRT + HDR brachytherapy boost	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Prostate-Specific Antigen (PSA) ng/mL <10	538 Participants n=5 Participants	530 Participants n=7 Participants	1068 Participants n=5 Participants
Prostate-Specific Antigen (PSA) ng/mL 10-20	212 Participants n=5 Participants	212 Participants n=7 Participants	424 Participants n=5 Participants
Gleason Score 2-6	64 Participants n=5 Participants	59 Participants n=7 Participants	123 Participants n=5 Participants
Gleason Score 7	686 Participants n=5 Participants	683 Participants n=7 Participants	1369 Participants n=5 Participants
T-Stage T1	493 Participants n=5 Participants	449 Participants n=7 Participants	942 Participants n=5 Participants
T-Stage T2	257 Participants n=5 Participants	293 Participants n=7 Participants	550 Participants n=5 Participants
N-Stage N0	611 Participants n=5 Participants	604 Participants n=7 Participants	1215 Participants n=5 Participants
N-Stage N1	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
N-Stage NX	136 Participants n=5 Participants	134 Participants n=7 Participants	270 Participants n=5 Participants
M-Stage M0	657 Participants n=5 Participants	666 Participants n=7 Participants	1323 Participants n=5 Participants
M-Stage M1	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
M-Stage MX	91 Participants n=5 Participants	76 Participants n=7 Participants	167 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=750 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=742 Participants 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).
Percentage of Participants Alive (Overall Survival)	90.0 percentage of participants Interval 87.7 to 92.2	91.0 percentage of participants Interval 88.8 to 93.1

SECONDARY outcome

Population: Eligible participants

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.

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=750 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=742 Participants 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).
Percentage of Participants With Biochemical Failure	13.9 percentage of participants Interval 11.5 to 16.6	7.7 percentage of participants Interval 5.9 to 9.9

SECONDARY outcome

Population: Eligible participants

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.

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=750 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=742 Participants 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).
Percentage of Participants With Local Recurrence	2.6 percentage of participants Interval 1.6 to 4.1	0.6 percentage of participants Interval 0.2 to 1.5

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Eligible participants

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.

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=750 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=742 Participants 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).
Percentage of Participants With Distant Metastasis	3.1 percentage of participants Interval 2.0 to 4.6	0.6 percentage of participants Interval 0.2 to 1.4

SECONDARY outcome

Population: Eligible participants

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.

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=750 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=742 Participants 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).
Percentage of Participants Dead Due to Prostate Cancer (Prostate Cancer-specific Mortality)	0.90 percentage of participants Interval 0.4 to 1.9	0 percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Population: Eligible participants

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.

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=750 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=742 Participants 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).
Percentage of Participants Dead Due to Cause Other Than Prostate Cancer (Non-Prostate Cancer-specific Mortality)	9.1 percentage of participants Interval 7.1 to 11.5	9.0 percentage of participants Interval 7.0 to 11.4

SECONDARY outcome

Population: Eligible participants

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.

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=750 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=742 Participants 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).
Percentage of Participants Receiving Salvage Androgen Deprivation Therapy (ADT)	6.1 percentage of participants Interval 4.5 to 8.1	4.2 percentage of participants Interval 2.8 to 5.8

SECONDARY outcome

Population: Eligible participants with radiation treatment data.

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=725 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=707 Participants 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).
Percentage of Participants Alive (Overall Survival) by Radiation Therapy Modality EBRT	89.4 percentage of participants Interval 86.9 to 91.9	90.3 percentage of participants Interval 87.9 to 92.8
Percentage of Participants Alive (Overall Survival) by Radiation Therapy Modality EBRT +LDR Brachytherapy Boost	100 percentage of participants Interval 100.0 to 100.0	97.2 percentage of participants Interval 93.3 to 100.0
Percentage of Participants Alive (Overall Survival) by Radiation Therapy Modality EBRT +HDR Brachytherapy Boost	91.7 percentage of participants Interval 76.0 to 100.0	100 percentage of participants Interval 100.0 to 100.0

SECONDARY outcome

Population: Eligible participants who started protocol treatment and have adverse event data

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.

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=733 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=725 Participants 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).
Number of Participants With Acute Adverse Events	152 Participants	504 Participants

SECONDARY outcome

Population: Eligible participants who started protocol treatment and have adverse event data

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.

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=733 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=725 Participants 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).
Percentage of Participants With Late Grade 3+ Adverse Events	12.8 percentage of participants Interval 10.5 to 15.4	15.2 percentage of participants Interval 12.6 to 17.9

SECONDARY outcome

Population: Eligible participants

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.

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=750 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=742 Participants 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).
Percentage of Participants Failed (Freedom From Failure)	14.8 percentage of participants Interval 12.2 to 17.5	7.9 percentage of participants Interval 6.0 to 10.1

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=215 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=205 Participants 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).
Change From Baseline in Expanded Prostate Cancer Index Composite (EPIC) Urinary Domain Score End of RT	-12.4 score on a scale Standard Deviation 17.0	-13.8 score on a scale Standard Deviation 15.4
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	-3.6 score on a scale Standard Deviation 15.3
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	-1.6 score on a scale Standard Deviation 15.3
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	0.3 score on a scale Standard Deviation 12.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=215 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=205 Participants 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).
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	-10.5 score on a scale Standard Deviation 13.7
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	-3.8 score on a scale Standard Deviation 9.6
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	-5.2 score on a scale Standard Deviation 13.4
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	-2.9 score on a scale Standard Deviation 10.7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=215 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=205 Participants 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).
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	-18.4 score on a scale Standard Deviation 16.2
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	-13.7 score on a scale Standard Deviation 16.9
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	-7.8 score on a scale Standard Deviation 14.4
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	-2.7 score on a scale Standard Deviation 13.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=215 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=205 Participants 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).
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	-16.6 score on a scale Standard Deviation 23.7
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	-22.6 score on a scale Standard Deviation 25.8
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 23.0	-19.9 score on a scale Standard Deviation 25.3
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	-9.6 score on a scale Standard Deviation 27.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Dose-Escalated Radiation Therapy Alone n=215 Participants 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=205 Participants 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).
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	1.84 score on a scale Standard Deviation 5.54
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	1.21 score on a scale Standard Deviation 5.34
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 6.00	0.86 score on a scale Standard Deviation 5.08
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	0.80 score on a scale Standard Deviation 5.62

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Dose-Escalated Radiation Therapy Alone

Serious events: 20 serious events

Other events: 597 other events

Deaths: 119 deaths

Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation

Serious events: 33 serious events

Other events: 647 other events

Deaths: 100 deaths

Serious adverse events

Other adverse events

Additional Information

Wendy Seiferheld

NRG Oncology

Phone: 215-574-3208

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	Dose-Escalated Radiation Therapy Alone n=733 participants at risk 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.	Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation n=725 participants at risk 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).
Blood and lymphatic system disorders Hemoglobin decreased	4.1% 30/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	10.2% 74/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Gastrointestinal disorders Constipation	11.7% 86/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	13.2% 96/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Gastrointestinal disorders Diarrhea	18.3% 134/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	25.7% 186/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Gastrointestinal disorders Gastrointestinal disorder	9.8% 72/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	10.6% 77/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Gastrointestinal disorders Hemorrhoids	5.9% 43/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	6.5% 47/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Gastrointestinal disorders Proctitis	14.3% 105/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	15.9% 115/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Gastrointestinal disorders Rectal hemorrhage	14.3% 105/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	12.8% 93/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
General disorders Fatigue	28.6% 210/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	46.6% 338/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
General disorders Pain [other]	5.0% 37/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	6.8% 49/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Investigations Alanine aminotransferase increased	0.27% 2/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	5.4% 39/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Musculoskeletal and connective tissue disorders Back pain	4.4% 32/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	6.3% 46/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Nervous system disorders Dizziness	1.6% 12/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	5.2% 38/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Psychiatric disorders Libido decreased	6.1% 45/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	16.7% 121/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Renal and urinary disorders Cystitis	10.1% 74/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	10.8% 78/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Renal and urinary disorders Urethral pain	4.1% 30/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	6.1% 44/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Renal and urinary disorders Urinary frequency	63.0% 462/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	73.2% 531/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Renal and urinary disorders Urinary incontinence	17.1% 125/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	18.8% 136/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Renal and urinary disorders Urinary retention	24.6% 180/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	30.6% 222/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Renal and urinary disorders Urogenital disorder	21.6% 158/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	27.6% 200/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Reproductive system and breast disorders Ejaculation disorder	4.6% 34/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	5.2% 38/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Reproductive system and breast disorders Erectile dysfunction	37.2% 273/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	49.5% 359/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.
Vascular disorders Hot flashes	3.1% 23/733 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.	57.1% 414/725 • 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. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment and had adverse event data.