Trial Outcomes & Findings for Radiation Therapy With or Without Bicalutamide for Recurrent pT3N0 Prostate Cancer After Radical Prostatectomy (NCT NCT00002874)

Last Updated: 2022-06-15

Results Overview

Overall survival rates were estimated by the Kaplan-Meier method, with failure defined as death by any cause. Four-year follow-up was required of all patients, twelve-year rates are reported. Four-year follow-up was required of all patients, but twelve-year rates were reported. Patients are followed until death.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

840 participants

Primary outcome timeframe

From date of randomization to 12 years.

Results posted on

2022-06-15

Participant Flow

Participant milestones

Participant milestones
Measure	Bicalutamide Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)	Placebo Radiation therapy (64.8 Gy) + placebo (daily 2 years)
Overall Study STARTED	421	419
Overall Study COMPLETED	376	384
Overall Study NOT COMPLETED	45	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Bicalutamide Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)	Placebo Radiation therapy (64.8 Gy) + placebo (daily 2 years)
Overall Study Withdrawal by Subject	1	1
Overall Study Protocol Violation	44	34

Baseline Characteristics

Radiation Therapy With or Without Bicalutamide for Recurrent pT3N0 Prostate Cancer After Radical Prostatectomy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bicalutamide n=376 Participants Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)	Placebo n=384 Participants Radiation therapy (64.8 Gy) + placebo (daily 2 years)	Total n=760 Participants Total of all reporting groups
Age, Continuous	65 years n=5 Participants	65 years n=7 Participants	65 years 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	376 Participants n=5 Participants	384 Participants n=7 Participants	760 Participants n=5 Participants

PRIMARY outcome

Timeframe: From date of randomization to 12 years.

Population: Eligible patients who did not withdraw consent.

Outcome measures

Outcome measures
Measure	Placebo n=394 Participants Radiation therapy (64.8 Gy) + placebo (daily 2 years)	Bicalutamide n=376 Participants Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)
Overall Survival (12-year Rates Reported)	71.3 percentage of participants Interval 66.5 to 76.0	76.3 percentage of participants Interval 71.9 to 80.8

SECONDARY outcome

Timeframe: From date of randomization to 12 years.

Population: Eligible patients who did not withdraw consent.

Non-prostate cancer death rates were estimated by the cumulative incidence method, with failure defined as any death that does not fall into the following categories: death due to prostate cancer or complications of protocol treatment (centrally reviewed), death with known progressive metastatic disease while on salvage hormone therapy, or death with a known rising PSA while on salvage hormone therapy. All other deaths are considered competing risks. Patients alive at time of analysis were censored. Any other death was treated as a competing risk. Four-year follow-up was required of all patients, but twelve-year rates were reported. Patients are followed until death. "Non-Prostate cancer death" is a more accurate wording for the protocol endpoint of "non-disease-specific survival", and matches the protocol definition.

Outcome measures

Outcome measures
Measure	Placebo n=376 Participants Radiation therapy (64.8 Gy) + placebo (daily 2 years)	Bicalutamide n=384 Participants Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)
Non-Prostate Cancer Death (12-year Rates Reported)	15.3 percentage of participants Interval 11.8 to 19.3	17.9 percentage of participants Interval 14.0 to 22.1

SECONDARY outcome

Timeframe: From date of randomization to 12 years.

Population: Eligible patients who did not withdraw consent.

Second PSA recurrence (SPSAR) rates (i.e. first PSA failure on study) were estimated by the cumulative incidence method, with failure defined as the first occurrence of one of the following events: 1. Increase in PSA following protocol treatment according to the following criteria met during protocol treatment: If PSA dropped to undetectable level (\<0.2 ng/ml) during protocol treatment (PT) then failure = increase after PT to \>= 0.5 ng/ml ; If PSA decreased to a detectable level (≥ 0.2 ng/ml) during PT, then failure = increase PT of \>= 0.3 ng/ml above the lowest detectable level; If PSA did not decrease during PT then failure = increase in PSA after PT of \>= 0.5 ng/ml above entry PSA level. 2. The start of salvage hormone therapy. Patients alive without SPSAR at time of analysis were censored. Death without SPSAR was treated as a competing risk. Four-year follow-up was required of all patients, but twelve-year rates were reported. Patients are followed until death.

Outcome measures

Outcome measures
Measure	Placebo n=376 Participants Radiation therapy (64.8 Gy) + placebo (daily 2 years)	Bicalutamide n=384 Participants Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)
Second PSA Recurrence (12-year Rates Reported)	67.9 percentage of participants Interval 62.7 to 72.5	44.0 percentage of participants Interval 38.8 to 49.1

SECONDARY outcome

Timeframe: From start of salvage hormone therapy to 12 years.

Population: Eligible patients who did not withdraw consent and who started salvage hormone therapy.

Third PSA recurrence rates (i.e. second PSA failure on study) were estimated by the cumulative incidence method, with failure defined as PSA value of 0.5ng/ml or higher or any disease progression after starting salvage hormone therapy. Patients alive without third PSA recurrence at time of analysis were censored. Death without third PSA recurrence was treated as a competing risk. Four-year follow-up was required of all patients, but twelve-year rates were reported. Patients are followed until death.

Outcome measures

Outcome measures
Measure	Placebo n=167 Participants Radiation therapy (64.8 Gy) + placebo (daily 2 years)	Bicalutamide n=111 Participants Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)
Third PSA Recurrence (12-year Rates Reported)	80.7 percentage of participants Interval 73.2 to 86.3	84.2 percentage of participants Interval 75.0 to 90.3

SECONDARY outcome

Timeframe: End of protocol treatment, which is planned to last for two years

Population: Eligible patients who did not withdraw consent.

Complete response is defined as a drop in PSA on protocol treatment to less than 0.2 ng/ml. Note that when the study opened many institutions could not detect PSA \< 05 ng/ml.

Outcome measures

Outcome measures
Measure	Placebo n=376 Participants Radiation therapy (64.8 Gy) + placebo (daily 2 years)	Bicalutamide n=384 Participants Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)
PSA Complete Response at End of Protocol Treatment	259 Participants	360 Participants

SECONDARY outcome

Timeframe: From date of randomization to 12 years.

Population: Eligible patients who did not withdraw consent.

Distant failure rates were estimated by the cumulative incidence method, with failure defined as the first occurrence of distant failure. Patients alive without distant metastases at time of analysis were censored. Death without distant metastasis was treated as a competing risk. Four-year follow-up was required of all patients, but twelve-year rates were reported. Patients are followed until death.

Outcome measures

Outcome measures
Measure	Placebo n=376 Participants Radiation therapy (64.8 Gy) + placebo (daily 2 years)	Bicalutamide n=384 Participants Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)
Distant Failure (12-year Rates Reported)	23.0 percentage of participants Interval 18.8 to 27.5	14.5 percentage of participants Interval 11.1 to 18.5

SECONDARY outcome

Timeframe: From date of randomization to 12 years.

Population: Eligible patients who did not withdraw consent.

Prostate cancer death rates were estimated by the cumulative incidence method, with failure defined as death due to prostate cancer or complications of protocol treatment (centrally reviewed), death with known progressive metastatic disease while on salvage hormone therapy, or death with a known rising PSA while on salvage hormone therapy. Patients alive at time of analysis were censored. Any other death was treated as a competing risk. Four-year follow-up was required of all patients, but twelve-year rates were reported. Patients are followed until death. "Prostate cancer death" is a more accurate wording for the protocol endpoint of "disease-specific survival", and matches the protocol definition.

Outcome measures

Outcome measures
Measure	Placebo n=376 Participants Radiation therapy (64.8 Gy) + placebo (daily 2 years)	Bicalutamide n=384 Participants Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)
Prostate Cancer Death (12-year Rates Reported)	13.4 percentage of participants Interval 10.1 to 17.2	5.8 percentage of participants Interval 3.6 to 8.6

SECONDARY outcome

Timeframe: From date of randomization to 12 years.

Population: Eligible patients who did not withdraw consent.

Progress-free survival rates were estimated by the Kaplan-Meier method, with failure defined as the first occurrence of PSA failure, local, regional or distant failure, or death from any cause. Patients alive without progression at time of analysis were censored. Four-year follow-up was required of all patients, but twelve-year rates were reported. Patients are followed until death. "Progression-free Survival" is more accurate wording for the protocol endpoint of "Freedom from Progression", and matches the protocol definition.

Outcome measures

Outcome measures
Measure	Placebo n=376 Participants Radiation therapy (64.8 Gy) + placebo (daily 2 years)	Bicalutamide n=384 Participants Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)
Progression-free Survival (12-year Rates Reported)	23.9 percentage of participants Interval 19.4 to 28.4	38.8 percentage of participants Interval 33.7 to 43.9

SECONDARY outcome

Timeframe: From date of randomization to four years.

Population: Eligible patients who started protocol treatment and did not withdraw consent.

Adverse events are graded using the Cooperative Group Common Toxicity Criteria and the Radiation Therapy Oncology Group (RTOG) Radiation Morbidity Scoring. Grade refers to severity, assigning Grades 1 through 5 based on this general guideline: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity. Toxicities reported to have occurred within 90 days from the start of radiotherapy are reported as "Acute Radiotherapy", all later toxicities are reported as "Hormone therapy and late radiotherapy toxicity". The highest grade toxicity event per subject is counted within each of these time periods. Four-year follow-up was required of all patients; patients are followed until death.

Outcome measures

Outcome measures
Measure	Placebo n=374 Participants Radiation therapy (64.8 Gy) + placebo (daily 2 years)	Bicalutamide n=382 Participants Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)
Grade 3+ Toxicity Acute radiotherapy toxicity	17 participants	8 participants
Grade 3+ Toxicity Hormone therapy and late radiotherapy toxicity	73 participants	100 participants

Adverse Events

Placebo

Serious events: 84 serious events

Other events: 346 other events

Deaths: 0 deaths

Bicalutamide

Serious events: 97 serious events

Other events: 374 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Wendy Seiferheld, M.S.

NRG Oncology

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	Placebo n=382 participants at risk Radiation therapy (64.8 Gy) + placebo (daily 2 years)	Bicalutamide n=374 participants at risk Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)
Blood and lymphatic system disorders Acute RT Toxicity: Hematologic: NOS	0.79% 3/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	0.53% 2/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Blood and lymphatic system disorders Hematologic: NOS	1.3% 5/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	1.3% 5/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Cardiac disorders Cardiac: NOS	4.7% 18/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	1.6% 6/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Gastrointestinal disorders Acute RT Toxicity: Bowel: NOS	0.26% 1/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	0.80% 3/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Gastrointestinal disorders Bowel/GI: NOS	2.6% 10/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	2.1% 8/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Gastrointestinal disorders Nausea/vomiting: NOS	0.26% 1/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	0.27% 1/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
General disorders Acute RT Toxicity: Other: NOS	0.00% 0/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	0.27% 1/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
General disorders Other: NOS	4.2% 16/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	4.3% 16/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
General disorders Pain: NOS	0.52% 2/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	1.6% 6/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Hepatobiliary disorders Liver: NOS	0.52% 2/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	0.27% 1/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Nervous system disorders Neurologic: NOS	2.1% 8/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	1.3% 5/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Renal and urinary disorders Acute RT Toxicity: Bladder: NOS	1.0% 4/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	2.9% 11/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Renal and urinary disorders Bladder/GU: NOS	7.3% 28/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	8.0% 30/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Reproductive system and breast disorders Impotence: NOS	7.3% 28/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	4.3% 16/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Respiratory, thoracic and mediastinal disorders Dyspnea: NOS	0.79% 3/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	0.27% 1/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Skin and subcutaneous tissue disorders Skin-general: NOS	0.52% 2/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	0.80% 3/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.

Measure	Placebo n=382 participants at risk Radiation therapy (64.8 Gy) + placebo (daily 2 years)	Bicalutamide n=374 participants at risk Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)
Blood and lymphatic system disorders Acute RT Toxicity: Hematologic: NOS	8.9% 34/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	7.5% 28/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Blood and lymphatic system disorders Hematologic: NOS	15.2% 58/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	9.6% 36/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Cardiac disorders Cardiac: NOS	5.5% 21/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	2.7% 10/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Gastrointestinal disorders Acute RT Toxicity: Bowel: NOS	60.7% 232/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	62.8% 235/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Gastrointestinal disorders Bowel/GI: NOS	50.3% 192/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	44.9% 168/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Gastrointestinal disorders Nausea/vomiting: NOS	5.0% 19/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	3.2% 12/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
General disorders Acute RT Toxicity: Other: NOS	17.8% 68/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	13.4% 50/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
General disorders Other: NOS	33.8% 129/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	26.7% 100/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
General disorders Pain: NOS	14.1% 54/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	17.4% 65/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Injury, poisoning and procedural complications Acute RT Toxicity: Skin: NOS	22.8% 87/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	23.5% 88/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Injury, poisoning and procedural complications Skin-within XRT field: NOS	12.0% 46/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	9.1% 34/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Nervous system disorders Neurologic: NOS	6.0% 23/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	7.0% 26/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Renal and urinary disorders Acute RT Toxicity: Bladder: NOS	49.2% 188/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	44.1% 165/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Renal and urinary disorders Bladder/GU: NOS	60.7% 232/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	59.4% 222/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Reproductive system and breast disorders Gynecomastia: NOS	69.6% 266/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	11.2% 42/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Reproductive system and breast disorders Impotence: NOS	12.0% 46/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	9.9% 37/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Skin and subcutaneous tissue disorders Skin-general: NOS	12.8% 49/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	4.0% 15/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.
Vascular disorders Hot flashes: NOS	21.7% 83/382 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.	17.9% 67/374 Subjects who started protocol treatment are included. Subjects experiencing more than one of a given toxicity are counted only once for that toxicity. Adverse events were graded with a combination of the Cooperative Group Common Toxicity Criteria and RTOG Acute and Late Radiation Morbidity Scoring. Grade refers to severity of toxicity assigning Grades 1-5: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity.