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Radiation Therapy With or Without Antiandrogen Therapy in Treating Patients With Stage I or Stage II Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00002597
Recruitment Status : Completed
First Posted : February 27, 2004
Results First Posted : June 6, 2017
Last Update Posted : June 14, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Prostate Cancer
Interventions Drug: flutamide
Drug: Zoladex
Drug: Lupron
Radiation: radiation therapy
Enrollment 2028
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Hormone Therapy + Radiation Therapy Radiation Therapy Alone
Hide Arm/Group Description Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy. Radiation therapy alone
Period Title: Overall Study
Started 1013 1015
Completed 987 [1] 992 [1]
Not Completed 26 23
Reason Not Completed
Protocol Violation             19             17
Withdrawal by Subject             7             6
[1]
Subjects with data available for the primary analysis are considered to have completed the study.
Arm/Group Title Hormone Therapy + Radiation Therapy Radiation Therapy Alone Total
Hide Arm/Group Description Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy. Radiation therapy alone Total of all reporting groups
Overall Number of Baseline Participants 987 992 1979
Hide Baseline Analysis Population Description
All eligible patients.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 987 participants 992 participants 1979 participants
70
(47 to 91)
71
(47 to 88)
71
(47 to 91)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 987 participants 992 participants 1979 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
987
 100.0%
992
 100.0%
1979
 100.0%
1.Primary Outcome
Title Overall Survival Rate (10-year)
Hide Description Overall survival (OS) was calculated from randomization to the date of death from any cause and overall survival rates were estimated by the Kaplan-Meier method.
Time Frame From date of randomization to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients.
Arm/Group Title Hormone Therapy + Radiation Therapy Radiation Therapy Alone
Hide Arm/Group Description:
Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.
Radiation therapy alone
Overall Number of Participants Analyzed 987 992
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
61.9
(58.3 to 65.3)
56.8
(53.2 to 60.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
Comments Null hypothesis: 8-year OS rate of 60% radiation therapy (RT) alone vs. 67% with hormone therapy. The study was designed with 90% power to detect a 7-percentage- point absolute difference in the 8-year survival rate, with the use of a one-sided log-rank test at the 0.025 significance level, requiring 1980 patients and 716 deaths for definitive analysis.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0309
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
1.01 to 1.35
Estimation Comments Reference level = Hormone Therapy + Radiation Therapy
2.Secondary Outcome
Title Disease-specific Survival Rate (10 Years)
Hide Description Disease-specific failure is defined as death certified as due to prostate cancer (by central review), death due to complications of treatment (irrespective of malignancy status), death from unknown causes with active malignancy, or death from unknown causes with previously documented relapse (either clinical or biochemical). Survival rates were estimated by means of cumulative incidence functions.
Time Frame From registration to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients.
Arm/Group Title Hormone Therapy + Radiation Therapy Radiation Therapy Alone
Hide Arm/Group Description:
Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.
Radiation therapy alone
Overall Number of Participants Analyzed 987 992
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
95.7
(94.3 to 97.2)
92.6
(90.8 to 94.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
Comments Gray's test was used to compare cumulative incidence between treatment arms (1-sided significance level of 0.025) and the Fine-Gray model was used to calculate hazard ratios.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Gray's test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.86
Confidence Interval (2-Sided) 95%
1.27 to 2.74
Estimation Comments Reference level = Hormone Therapy + Radiation Therapy
3.Secondary Outcome
Title Local Progression Rate (10 Years)
Hide Description Local progression defined as documented local progression as determined by clinical exam . Failure rates were estimated by means of cumulative incidence functions.
Time Frame From registration to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients.
Arm/Group Title Hormone Therapy + Radiation Therapy Radiation Therapy Alone
Hide Arm/Group Description:
Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.
Radiation therapy alone
Overall Number of Participants Analyzed 987 992
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
10.9
(8.8 to 12.9)
16.1
(13.7 to 18.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
Comments Gray's test was used to compare cumulative incidence between treatment arms (1-sided significance level of 0.025) and the Fine-Gray model was used to calculate hazard ratios.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0013
Comments [Not Specified]
Method Gray's test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
1.17 to 1.93
Estimation Comments Reference level = Hormone Therapy + Radiation Therapy
4.Secondary Outcome
Title Distant Failure Rate (10 Years)
Hide Description Failure is defined as documented metastatic disease. Failure rates were estimated by means of cumulative incidence functions.
Time Frame From registration to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients.
Arm/Group Title Hormone Therapy + Radiation Therapy Radiation Therapy Alone
Hide Arm/Group Description:
Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.
Radiation therapy alone
Overall Number of Participants Analyzed 987 992
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
5.5
(3.9 to 7.0)
8.0
(6.2 to 9.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
Comments Gray's test was used to compare cumulative incidence between treatment arms (1-sided significance level of 0.025) and the Fine-Gray model was used to calculate hazard ratios.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments [Not Specified]
Method Gray's test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.45
Confidence Interval (2-Sided) 95%
1.03 to 2.06
Estimation Comments Reference level = Hormone Therapy + Radiation Therapy
5.Secondary Outcome
Title Biochemical Failure Rate (10 Years)
Hide Description The Phoenix definition of biochemical failure was used - an increase in the prostate-specific antigen (PSA) level of >2 ng per milliliter above the nadir. Failure rates were estimated by means of cumulative incidence functions.
Time Frame From registration to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients.
Arm/Group Title Hormone Therapy + Radiation Therapy Radiation Therapy Alone
Hide Arm/Group Description:
Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.
Radiation therapy alone
Overall Number of Participants Analyzed 987 992
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
26.3
(23.4 to 29.2)
41.1
(37.9 to 44.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
Comments Gray's test was used to compare cumulative incidence between treatment arms (1-sided significance level of 0.025) and the Fine-Gray model was used to calculate hazard ratios.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Gray's test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.74
Confidence Interval (2-Sided) 95%
1.48 to 2.04
Estimation Comments Reference level = Hormone Therapy + Radiation Therapy
6.Secondary Outcome
Title Clinical Relapse Rate (10 Years)
Hide Description Clinical relapse is defined as local progression or distant metastases. Failure rates were estimated by means of cumulative incidence functions.
Time Frame From registration to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients.
Arm/Group Title Hormone Therapy + Radiation Therapy Radiation Therapy Alone
Hide Arm/Group Description:
Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.
Radiation therapy alone
Overall Number of Participants Analyzed 987 992
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
15.0
(12.6 to 17.3)
21.7
(19.1 to 24.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
Comments Gray's test was used to compare cumulative incidence between treatment arms (1-sided significance level of 0.025) and the Fine-Gray model was used to calculate hazard ratios.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Gray's test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
1.21 to 1.85
Estimation Comments Reference level = Hormone Therapy + Radiation Therapy
7.Secondary Outcome
Title Second Biochemical Relapse Rate (10 Years)
Hide Description Second biochemical relapse is as defined as follows (after initiation of salvage hormone therapy): A rise in PSA on at least two consecutive cases above the nadir (after initiation of salvage hormone therapy), with the rises in PSA exceeding 1 ng/ml above the nadir; or failure to reach 4 ng/L or less at 18 months. The rates of second biochemical relapse were estimated by means of cumulative incidence functions.
Time Frame From registration to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients.
Arm/Group Title Hormone Therapy + Radiation Therapy Radiation Therapy Alone
Hide Arm/Group Description:
Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.
Radiation therapy alone
Overall Number of Participants Analyzed 987 992
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
2.7
(1.6 to 3.8)
6.1
(4.4 to 7.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
Comments Gray's test was used to compare cumulative incidence between treatment arms (1-sided significance level of 0.025) and the Fine-Gray model was used to calculate hazard ratios.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Gray's test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.06
Confidence Interval (2-Sided) 95%
1.34 to 3.16
Estimation Comments Reference level = Hormone Therapy + Radiation Therapy
8.Secondary Outcome
Title Disease-free Survival Rate (10 Years)
Hide Description Disease-free failure is defined as documentation of progression (local progression, distant failure, and biochemical failure) or death from any cause. Disease-free survival rates were estimated by the Kaplan-Meier method.
Time Frame From registration to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients.
Arm/Group Title Hormone Therapy + Radiation Therapy Radiation Therapy Alone
Hide Arm/Group Description:
Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.
Radiation therapy alone
Overall Number of Participants Analyzed 987 992
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
51.7
(48.1 to 55.1)
39.5
(36.1 to 42.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
Comments Treatment arms were compared using the log-rank test (one-sided significance level of 0.025).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.38
Confidence Interval (2-Sided) 95%
1.22 to 1.56
Estimation Comments Reference level = Hormone Therapy + Radiation Therapy
9.Secondary Outcome
Title Positive Re-biopsy Rate at Two Years
Hide Description The rate of prostate rebiopsy at two years is defined as the proportion of patients whose results are positive among all eligible patients who had a repeat biopsy at two years. The rate was estimated separately in each arm.
Time Frame From registration to two years
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients who had a repeat biopsy at 2 years.
Arm/Group Title Hormone Therapy + Radiation Therapy Radiation Therapy Alone
Hide Arm/Group Description:
Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.
Radiation therapy alone
Overall Number of Participants Analyzed 439 404
Measure Type: Number
Unit of Measure: percentage of participants
20.2 38.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description Eligible patients who received treatment. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
 
Arm/Group Title Neoadjuvant TAS 2 Months Before and During RT Radiation Therapy Alone
Hide Arm/Group Description Neoadjuvant Total Androgen Suppression (TAS) two months before and during radiation therapy Radiation therapy alone
All-Cause Mortality
Neoadjuvant TAS 2 Months Before and During RT Radiation Therapy Alone
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Neoadjuvant TAS 2 Months Before and During RT Radiation Therapy Alone
Affected / at Risk (%) Affected / at Risk (%)
Total   33/1003 (3.29%)   16/1003 (1.60%) 
Blood and lymphatic system disorders     
Acute RT Toxicity: Hematologic: NOS † 1  7/1003 (0.70%)  5/1003 (0.50%) 
Hormone Toxicity: Hematologic : NOS † 2  1/1003 (0.10%)  0/1003 (0.00%) 
Late RT Toxicity: Hematologic: NOS † 3  8/1003 (0.80%)  3/1003 (0.30%) 
Gastrointestinal disorders     
Acute RT Toxicity: Bowel: NOS † 1  1/1003 (0.10%)  0/1003 (0.00%) 
Late RT Toxicity: Bowel: NOS † 3  1/1003 (0.10%)  3/1003 (0.30%) 
Late RT Toxicity: Other GI: NOS † 3  2/1003 (0.20%)  0/1003 (0.00%) 
General disorders     
Late RT Toxicity: Other: NOS † 3  3/1003 (0.30%)  0/1003 (0.00%) 
Hepatobiliary disorders     
Hormone Toxicity: Liver : NOS † 2  3/1003 (0.30%)  0/1003 (0.00%) 
Renal and urinary disorders     
Acute RT Toxicity: Bladder: NOS † 1  4/1003 (0.40%)  4/1003 (0.40%) 
Late RT Toxicity: Bladder: NOS † 3  12/1003 (1.20%)  0/1003 (0.00%) 
Late RT Toxicity: Other GU: NOS † 3  0/1003 (0.00%)  1/1003 (0.10%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, RTOG Acute RT Morb.
2
Term from vocabulary, Coop. Group CTC 1989
3
Term from vocabulary, RTOG/EORTC Late Tox.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Neoadjuvant TAS 2 Months Before and During RT Radiation Therapy Alone
Affected / at Risk (%) Affected / at Risk (%)
Total   975/1003 (97.21%)   955/1003 (95.21%) 
Blood and lymphatic system disorders     
Acute RT Toxicity: Hematologic: NOS † 1  127/1003 (12.66%)  67/1003 (6.68%) 
Hormone Toxicity: Hematologic : NOS † 2  172/1003 (17.15%)  0/1003 (0.00%) 
Late RT Toxicity: Hematologic: NOS † 3  135/1003 (13.46%)  109/1003 (10.87%) 
Gastrointestinal disorders     
Acute RT Toxicity: Bowel: NOS † 1  439/1003 (43.77%)  501/1003 (49.95%) 
Late RT Toxicity: Bowel: NOS † 3  262/1003 (26.12%)  210/1003 (20.94%) 
General disorders     
Acute RT Toxicity: Other: NOS † 1  135/1003 (13.46%)  138/1003 (13.76%) 
Late RT Toxicity: Other: NOS † 3  84/1003 (8.37%)  99/1003 (9.87%) 
Hepatobiliary disorders     
Hormone Toxicity: Liver : NOS † 2  93/1003 (9.27%)  0/1003 (0.00%) 
Renal and urinary disorders     
Acute RT Toxicity: Bladder: NOS † 1  149/1003 (14.86%)  190/1003 (18.94%) 
Late RT Toxicity: Bladder: NOS † 3  182/1003 (18.15%)  166/1003 (16.55%) 
Reproductive system and breast disorders     
Hormone Toxicity: Impotence : NOS † 2  238/1003 (23.73%)  0/1003 (0.00%) 
Late RT Toxicity: Other GU: NOS † 3  69/1003 (6.88%)  78/1003 (7.78%) 
Vascular disorders     
Hormone Toxicity: Hot flashes : NOS † 2  295/1003 (29.41%)  0/1003 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, RTOG Acute RT Morb.
2
Term from vocabulary, Coop. Group CTC 1989
3
Term from vocabulary, RTOG/EORTC Late Tox.
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Wendy Seiferheld, M.S.
Organization: NRG Oncology
EMail: seiferheldw@nrgoncology.org
Publications of Results:
Jones CU, Hunt D, McGowan DG, Amin MB, Chetner MP, Bruner DW, Leibenhaut MH, Husain SM, Rotman M, Souhami L, Sandler HM, Shipley WU. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med. 2011 Jul 14;365(2):107-18. doi: 10.1056/NEJMoa1012348.
McGowan D, Hunt D, Jones C, et al.: Effect of short-term endocrine therapy prior to and during radiation therapy on overall survival in patients with T1b-T2b adenocarcinoma of the prostate and PSA equal to or less than 20: initial results of RTOG 94-08. [Abstract] 2010 Genitourinary Cancers Symposium, March 5-7, 2010, San Francisco, California. A-6, 2010.
Other Publications:
Bruner D, Scott C, McGowan D, et al.: Factors influencing sexual outcomes in prostate cancer patients enrolled on radiation therapy oncology group studies 90-20 and 94-08. [Abstract] Proceedings of the International Society for Quality of Life Research 7: 575, 1998.
Bruner DW, Scott CB, McGowan D, et al.: Validation of the sexual adjustment questionnaire (SAQ) in prostate cancer patients enrolled on Radiation Therapy Oncology Group studies 90-20 and 94-08. [Abstract] Int J Radiat Oncol Biol Phys 42 (suppl 1): A-156, 202, 1998.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00002597    
Other Study ID Numbers: RTOG-9408
CDR0000063821
First Submitted: November 1, 1999
First Posted: February 27, 2004
Results First Submitted: May 8, 2017
Results First Posted: June 6, 2017
Last Update Posted: June 14, 2018