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Trial record 28 of 1441 for:    prostate cancer AND radiation

Interstitial Brachytherapy With or Without External-Beam Radiation Therapy in Treating Patients With 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: NCT00063882
Recruitment Status : Active, not recruiting
First Posted : July 9, 2003
Results First Posted : October 16, 2019
Last Update Posted : October 16, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
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 Radiation: Brachytherapy (100/110)
Radiation: Brachytherapy (125/145)
Radiation: External Beam Radiation Therapy
Enrollment 588
Recruitment Details  
Pre-assignment Details  
Arm/Group Title EBRT + Brachytherapy Brachytherapy Only
Hide Arm/Group Description External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110) Transperineal interstitial permanent brachytherapy (125/145)
Period Title: Overall Study
Started 292 296
Has Acute Adverse Event Data [1] 282 288
Has Late Adverse Event Data [2] 282 287
Has Baseline/4-month EPIC Data [3] 222 241
Has Baseline/24-month EPIC Data [4] 201 219
Eligible Patients 287 292
Completed [5] 287 292
Not Completed 5 4
Reason Not Completed
Protocol Violation             3             3
Withdrawal by Subject             2             1
[1]
Eligible patients who started study treatment
[2]
Eligible patients who started study treatment and are alive 181 days after start of radiation
[3]
Eligible patients with baseline and 4-month EPIC data after start of radiation
[4]
Eligible patients with baseline and 24-month EPIC data after start of radiation
[5]
Subjects contributing any data to analysis are considered to have completed the study.
Arm/Group Title EBRT + Brachytherapy Brachytherapy Only Total
Hide Arm/Group Description External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110) Transperineal interstitial permanent brachytherapy (125/145) Total of all reporting groups
Overall Number of Baseline Participants 287 292 579
Hide Baseline Analysis Population Description
Eligible Patients
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 292 participants 579 participants
≤ 59
41
  14.3%
51
  17.5%
92
  15.9%
60-69
141
  49.1%
134
  45.9%
275
  47.5%
70-79
102
  35.5%
103
  35.3%
205
  35.4%
≥ 80
3
   1.0%
4
   1.4%
7
   1.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 292 participants 579 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
287
 100.0%
292
 100.0%
579
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 292 participants 579 participants
Hispanic or Latino
10
   3.5%
10
   3.4%
20
   3.5%
Not Hispanic or Latino
274
  95.5%
275
  94.2%
549
  94.8%
Unknown or Not Reported
3
   1.0%
7
   2.4%
10
   1.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 292 participants 579 participants
American Indian or Alaska Native
3
   1.0%
2
   0.7%
5
   0.9%
Asian
5
   1.7%
11
   3.8%
16
   2.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
50
  17.4%
52
  17.8%
102
  17.6%
White
223
  77.7%
226
  77.4%
449
  77.5%
More than one race
2
   0.7%
0
   0.0%
2
   0.3%
Unknown or Not Reported
4
   1.4%
1
   0.3%
5
   0.9%
Baseline Prostate Specific Antigen (PSA)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 292 participants 579 participants
0-<10 ng/ml
256
  89.2%
261
  89.4%
517
  89.3%
10-20 ng/ml
31
  10.8%
31
  10.6%
62
  10.7%
[1]
Measure Description: Prostate-specific antigen (PSA) is a protein made by the prostate gland and found in the blood. PSA blood levels may be higher than normal in men who have prostate cancer, benign prostatic hyperplasia (BPH), or infection or inflammation of the prostate gland.
Zubrod Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 292 participants 579 participants
0
275
  95.8%
281
  96.2%
556
  96.0%
1
12
   4.2%
11
   3.8%
23
   4.0%
[1]
Measure Description: Measure Description: 0 - Asymptomatic; 1 - Symptomatic but completely ambulatory; 2 - Symptomatic, <50% in bed during the day; 3 - Symptomatic, >50% in bed, but not bedbound; 4 - Bedbound; 5 - Death
Combined Gleason Score (GS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 292 participants 579 participants
≤ 6
31
  10.8%
32
  11.0%
63
  10.9%
7
256
  89.2%
260
  89.0%
516
  89.1%
[1]
Measure Description: Gleason score describes prostate cancer based on how abnormal the cancer cells in a biopsy sample look under a microscope. Cells are scored 1-5 with 1 indicating "low-grade" looking similar to normal cells and 5 indicating "high-grade" barely resembling normal cells due to mutation. A pathologist assigns a Gleason grade to the first and second most predominant patterns in the biopsy. The two grades are added together to calculate the Gleason score (between 2 and 10). Cancers with lower scores tend to be less aggressive, while cancers with higher scores end to be more aggressive.
Gleason Score & PSA  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 292 participants 579 participants
GS<7 and PSA 10-20
31
  10.8%
32
  11.0%
63
  10.9%
GS 7 and PSA < 10
256
  89.2%
260
  89.0%
516
  89.1%
T Stage   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 292 participants 579 participants
T1
191
  66.6%
195
  66.8%
386
  66.7%
T2
96
  33.4%
97
  33.2%
193
  33.3%
[1]
Measure Description: Tumor stage per the American Joint Committee on Cancer (AJCC) 6th ed. refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. T's may be further divided to provide more detail, such as T3a and T3b.
Neoadjuvant Hormone Therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 287 participants 292 participants 579 participants
Yes
22
   7.7%
25
   8.6%
47
   8.1%
No
265
  92.3%
267
  91.4%
532
  91.9%
1.Primary Outcome
Title 5-Year Freedom From Progression Rate
Hide Description A Freedom from Progression (FFP) failure includes biochemical failure, local failure, distant failure, or death due to any cause. Patients who are failure free with less than 5 years of follow-up or who receive any secondary salvage therapy are censored. Freedom from Progression rates are estimated using the Kaplan-Meier method.
Time Frame From randomization to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
All Eligible Patients
Arm/Group Title EBRT + Brachytherapy Brachytherapy Only
Hide Arm/Group Description:
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
Transperineal interstitial permanent brachytherapy (125/145)
Overall Number of Participants Analyzed 287 292
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
85.5
(81.3 to 89.7)
83.1
(78.7 to 87.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Target sample size was 586; 532 patients were needed to test hypothesis of better FFP in the EBRT + Brachytherapy arm over the Brachytherapy Only arm. The trial is designed to detect a 10% improvement in 5-year FFP with 90% power, 1-sided alpha of 0.025. The Z-test statistic for the difference between the 2 5-year FFP rates with the standard errors estimated by Greenwood’s method will be used.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.21
Comments One-sided significance level of 0.025
Method Greenwood's T
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.60 to 1.12
Estimation Comments Reference level = Brachytherapy only
2.Secondary Outcome
Title Biochemical Failure Rate (Protocol Definition)
Hide Description Biochemical failure is defined as having 3 consecutive rises of post-treatment PSA or starting hormones after one or more elevations in post-treatment PSA but before 3 consecutive elevations are documented. The sum of the 3 consecutive rises must exceed 1 ng/mL above the nadir. If 3 consecutive PSA rises occur during the first 24 months followed by a subsequent non-hormonal induced PSA decrease, patients will not be considered PSA failures. Three consecutive rises with any of the 3 PSA values occurring more than 24 months after the implant procedure will constitute a failure. Time to biochemical is defined as time from randomization to the date of first biochemical failure, last known follow-up (censored), or death without biochemical failure (competing risk). Biochemical failure rates are estimated using the cumulative incidence method. Five year rates are reported.
Time Frame From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.9 years.
Hide Outcome Measure Data
Hide Analysis Population Description
All Eligible Patients
Arm/Group Title EBRT + Brachytherapy Brachytherapy Only
Hide Arm/Group Description:
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
Transperineal interstitial permanent brachytherapy (125/145)
Overall Number of Participants Analyzed 287 292
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
10.5
(7.2 to 14.4)
10.5
(7.3 to 14.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.95
Comments One-sided significance level of 0.025
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.63 to 1.54
Estimation Comments Reference level = Brachytherapy Only
3.Secondary Outcome
Title Biochemical Failure (Phoenix Definition)
Hide Description Biochemical Failure is defined as an increase of 2 ng/ml or more in PSA over the nadir PSA after 24 months from the start of treatment or the start of salvage hormones. Time to biochemical is defined as time from randomization to the date of first biochemical failure, last known follow-up (censored), or death without biochemical failure (competing risk). Biochemical failure rates are estimated using the cumulative incidence method. Five year rates are reported.
Time Frame From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years.Maximum follow-up at time of analysis was 13.9 years.
Hide Outcome Measure Data
Hide Analysis Population Description
All Eligible Patients
Arm/Group Title EBRT + Brachytherapy Brachytherapy Only
Hide Arm/Group Description:
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
Transperineal interstitial permanent brachytherapy (125/145)
Overall Number of Participants Analyzed 287 292
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
8.0
(5.2 to 11.6)
8.1
(5.3 to 11.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.97
Comments One-sided significance level of 0.025
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.64 to 1.58
Estimation Comments Reference level = Brachytherapy Only
4.Secondary Outcome
Title Prostate Cancer Death
Hide Description Prostate cancer death is defined as death due to prostate cancer or complications of treatment or death associated with any of the following: 1) further clinical tumor progression occurring after initiation of salvage androgen suppression therapy; 2) a rise that exceeds 1.0 ng/ml in the serum PSA level on at least two consecutive occasions that occurs during or after salvage androgen suppression therapy; and 3) disease progression in the absence of any anti-tumor therapy. Time to prostate cancer death is defined as time from randomization to the date of prostate cancer death, last known follow-up (censored), or death without prostate cancer (competing risk). Prostate cancer death rates are estimated using the cumulative incidence method. Five year rates are reported.
Time Frame From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.9 years.
Hide Outcome Measure Data
Hide Analysis Population Description
All Eligible Patients
Arm/Group Title EBRT + Brachytherapy Brachytherapy Only
Hide Arm/Group Description:
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
Transperineal interstitial permanent brachytherapy (125/145)
Overall Number of Participants Analyzed 287 292
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.4
(0.0 to 1.9)
1.1
(0.3 to 2.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.77
Comments One-sided significance level of 0.025
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.19
Confidence Interval (2-Sided) 95%
0.36 to 3.90
Estimation Comments Reference level = Brachytherapy Only
5.Secondary Outcome
Title Local Failure
Hide Description Failure is defined as progression (increase in palpable abnormality) at any time, failure of regression of the palpable tumor by two years, and redevelopment of a palpable abnormality after complete disappearance of previous abnormalities. Histologic criteria for local failure are presence of prostatic carcinoma upon biopsy and positive biopsy of the palpably normal prostate more than two years after the start of treatment. Time to local failure is defined as time from randomization to the date of first local failure, last known follow-up (censored), or death without local failure (competing risk). Local failure rates are estimated using the cumulative incidence method. Five year rates are reported.
Time Frame From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.9 years.
Hide Outcome Measure Data
Hide Analysis Population Description
All Eligible Patients
Arm/Group Title EBRT + Brachytherapy Brachytherapy Only
Hide Arm/Group Description:
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
Transperineal interstitial permanent brachytherapy (125/145)
Overall Number of Participants Analyzed 287 292
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
1.5
(0.5 to 3.5)
1.1
(0.3 to 2.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.99
Comments One-sided significance level of 0.025
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.33 to 3.13
Estimation Comments Reference level = Brachytherapy Only
6.Secondary Outcome
Title Distant Metastases
Hide Description Failure is defined as the appearance of any distant metastases. Time to distant metastases is defined as time from randomization to the date of first distant metastases, last known follow-up (censored), or death without distant metastases (competing risk). Distant metastases rates are estimated using the cumulative incidence method. Five year rates are reported.
Time Frame From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.9 years.
Hide Outcome Measure Data
Hide Analysis Population Description
All Eligible Patients
Arm/Group Title EBRT + Brachytherapy Brachytherapy Only
Hide Arm/Group Description:
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
Transperineal interstitial permanent brachytherapy (125/145)
Overall Number of Participants Analyzed 287 292
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
2.9
(1.4 to 5.4)
2.1
(0.9 to 4.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.81
Comments One-sided significance level of 0.025
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.46 to 2.76
Estimation Comments Reference level = Brachytherapy Only
7.Secondary Outcome
Title Overall Survival
Hide Description Failure is defined as death due to any cause. Overall survival time is defined as time from randomization to the date of death or last known follow-up (censored). Survival rates are estimated using the Kaplan-Meier method. Five year rates are reported.
Time Frame From randomization to last follow-up. Analysis occurs after all patients had been on study for at least 5 years. Maximum follow-up at time of analysis was 13.9 years.
Hide Outcome Measure Data
Hide Analysis Population Description
All Eligible Patients
Arm/Group Title EBRT + Brachytherapy Brachytherapy Only
Hide Arm/Group Description:
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
Transperineal interstitial permanent brachytherapy (125/145)
Overall Number of Participants Analyzed 287 292
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
95.3
(92.8 to 97.8)
93.2
(90.3 to 96.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments One-sided significance level of 0.025
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.51 to 1.17
Estimation Comments Reference level = Brachytherapy Only
8.Secondary Outcome
Title Percentage of Patients With Acute Grade 2+ and Grade 3+ Toxicities [Genitourinary (GU), Gastrointestinal (GI), and Overall]
Hide Description Acute toxicities are scored according to NCI Common Toxicity Criteria (CTC) version 2.0 and will be defined as the worst severity of the toxicity occurring ≤ 180 days from start of radiation. The CTC v 2.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to based.
Time Frame Zero to 180 days from the start of radiation
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients who started study treatment
Arm/Group Title EBRT + Brachytherapy Brachytherapy Only
Hide Arm/Group Description:
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
Transperineal interstitial permanent brachytherapy (125/145)
Overall Number of Participants Analyzed 282 288
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Grade 2+ GU/GI
24.1
(19.5 to 29.4)
21.9
(17.5 to 27.0)
Grade 2+ Overall
27.7
(22.8 to 33.2)
26.4
(21.6 to 31.8)
Grade 3+ GU/GI
6.0
(3.7 to 9.5)
5.6
(3.4 to 8.9)
Grade 3+ Overall
7.8
(5.2 to 11.6)
8.3
(5.6 to 12.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Grade 2+ GU/GI
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.53
Comments One-sided significance level of 0.05
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.76 to 1.67
Estimation Comments Reference level = Brachytherapy Only
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Grade 2+ Overall
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.73
Comments One-sided significance level of 0.05
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.73 to 1.53
Estimation Comments Reference level = Brachytherapy Only
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Grade 3+ GU/GI
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.81
Comments One-sided significance level of 0.05
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.54 to 2.19
Estimation Comments Reference level = Brachytherapy Only
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Grade 3+ Overall
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.82
Comments One-sided significance level of 0.05
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.51 to 1.69
Estimation Comments Reference level = Brachytherapy Only
9.Secondary Outcome
Title Time to Late Grade 3+ Toxicities [Genitourinary (GU), Gastrointestinal (GI), and Overall]
Hide Description Late toxicities are scored according to the Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) Late Radiation Morbidity Scoring Scheme and will be defined as the worst severity of the toxicity occurring > 180 days from radiation start. Grade 3+ GU/GI and overall were analyzed. RTOG/EORTC Late Radiation Morbidity Scoring Scheme assigns Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity. Time to late grade 3+ toxicity is defined as time from randomization to the date of first late grade 3+ toxicity, last known follow-up (censored), or death without late grade 3+ toxicity (competing risk). Late grade 3+ toxicity rates are estimated using the cumulative incidence method. Five year rates are reported.
Time Frame From 181 days after the start of radiation to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients who started study treatment and had follow-up data > 180 days from the start of treatment
Arm/Group Title EBRT + Brachytherapy Brachytherapy Only
Hide Arm/Group Description:
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
Transperineal interstitial permanent brachytherapy (125/145)
Overall Number of Participants Analyzed 282 287
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Grade 3+ GU/GI
7.9
(5.1 to 11.4)
3.8
(2.0 to 6.5)
Grade 3+ Overall
10.4
(7.2 to 14.3)
6.6
(4.1 to 9.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Grade 3+ GU/GI
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments One-sided significance level of 0.025
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.37
Confidence Interval (2-Sided) 95%
1.20 to 4.68
Estimation Comments Reference level = Brachytherapy Only
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Grade 3+ Overall
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments One-sided significance level of 0.025
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.81
Confidence Interval (2-Sided) 95%
1.06 to 3.10
Estimation Comments Reference level = Brachytherapy Only
10.Secondary Outcome
Title Change in Health-related Quality of Life From Baseline to 4-Months as Measured by Expanded Prostate Cancer Index Composite (EPIC)
Hide Description The EPIC form is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal function). The urinary domain summary score can be separated into 2 distinct subscales: urinary incontinence and urinary irritative. Hormonal domain was excluded as concurrent use of hormones was exclusionary and prior neoadjuvant hormone use was low. Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. The change score was calculated as the value at 4 months minus the value at baseline. A negative change reflects a decline at 4 months and a positive change reflects an improvement at 4 months.
Time Frame Baseline and 4 months after start of radiation
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients with baseline and 4-month EPIC data
Arm/Group Title EBRT + Brachytherapy Brachytherapy Only
Hide Arm/Group Description:
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
Transperineal interstitial permanent brachytherapy (125/145)
Overall Number of Participants Analyzed 222 241
Mean (Standard Deviation)
Unit of Measure: units on a scale
Urinary Number Analyzed 214 participants 234 participants
-20.1  (15.4) -14.1  (14.8)
Urinary-Incontinence Number Analyzed 204 participants 230 participants
-10.3  (17.7) -8.7  (17.7)
Urinary-Irritative Number Analyzed 211 participants 232 participants
-23.6  (18.1) -15.9  (17.3)
Bowel Number Analyzed 218 participants 234 participants
-10.4  (13.6) -6.3  (12.7)
Sexual Number Analyzed 211 participants 216 participants
-13.7  (22.3) -11.2  (21.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Urinary
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Significance level of 0.01
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect size
Estimated Value 0.40
Estimation Comments Minimally important difference (MID) defined as an effect size of at least 0.5. Effect sizes are interpreted as negligible: < 0.3; small: 0.3 to < 0.5; moderate: 0.5 to < 0.7; and large ≥ 0.7.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Urinary- Incontinence
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.33
Comments significance level of 0.01
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect size
Estimated Value 0.09
Estimation Comments Minimally important difference (MID) defined as an effect size of at least 0.5. Effect sizes are interpreted as negligible: < 0.3; small: 0.3 to < 0.5; moderate: 0.5 to < 0.7; and large ≥ 0.7.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Urinary-Irritative
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments significance level of 0.01
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect size
Estimated Value 0.44
Estimation Comments Minimally important difference (MID) defined as an effect size of at least 0.5. Effect sizes are interpreted as negligible: < 0.3; small: 0.3 to < 0.5; moderate: 0.5 to < 0.7; and large ≥ 0.7.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Bowel
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments significance level of 0.01
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect size
Estimated Value 0.31
Estimation Comments Minimally important difference (MID) defined as an effect size of at least 0.5. Effect sizes are interpreted as negligible: < 0.3; small: 0.3 to < 0.5; moderate: 0.5 to < 0.7; and large ≥ 0.7.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Sexual
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.23
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect size
Estimated Value 0.12
Estimation Comments [Not Specified]
Other Statistical Analysis Minimally important difference (MID) defined as an effect size of at least 0.5. Effect sizes are interpreted as negligible: < 0.3; small: 0.3 to < 0.5; moderate: 0.5 to < 0.7; and large ≥ 0.7.
11.Secondary Outcome
Title Change in Health-Related Quality of Life From Baseline to 24-Months as Measured by EPIC
Hide Description The EPIC form is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal function). The urinary domain summary score can be separated into 2 distinct subscales: urinary incontinence and urinary irritative. Hormonal domain was excluded as concurrent use of hormones was exclusionary and prior neoadjuvant hormone use was low. Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. The change score was calculated as the value at 24 months minus the value at baseline. A negative change reflects a decline at 24 months and a positive change reflects an improvement at 24 months.
Time Frame Baseline and 24 months after start of radiation
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients with baseline and 24-month EPIC data
Arm/Group Title EBRT + Brachytherapy Brachytherapy Only
Hide Arm/Group Description:
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
Transperineal interstitial permanent brachytherapy (125/145)
Overall Number of Participants Analyzed 201 219
Mean (Standard Deviation)
Unit of Measure: units on a scale
Urinary Number Analyzed 198 participants 211 participants
-11.2  (15.7) -5.6  (13.6)
Urinary- Incontinence Number Analyzed 192 participants 207 participants
-7.6  (17.7) -6.3  (15.5)
Urinary-Irritative Number Analyzed 195 participants 210 participants
-11.9  (17.4) -4.8  (14.3)
Bowel Number Analyzed 195 participants 213 participants
-7.1  (12.6) -2.4  (9.9)
Sexual Number Analyzed 190 participants 201 participants
-16.7  (23.4) -10.6  (21.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Urinary
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments Significance level of 0.01
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect size
Estimated Value 0.38
Estimation Comments Minimally important difference (MID) defined as an effect size of at least 0.5. Effect sizes are interpreted as negligible: < 0.3; small: 0.3 to < 0.5; moderate: 0.5 to < 0.7; and large ≥ 0.7.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Urinary-Incontinence
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.42
Comments Significance level of 0.01
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect size
Estimated Value 0.08
Estimation Comments Minimally important difference (MID) defined as an effect size of at least 0.5. Effect sizes are interpreted as negligible: < 0.3; small: 0.3 to < 0.5; moderate: 0.5 to < 0.7; and large ≥ 0.7.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Urinary-Irritative
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Significance level of 0.01
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect size
Estimated Value 0.44
Estimation Comments Minimally important difference (MID) defined as an effect size of at least 0.5. Effect sizes are interpreted as negligible: < 0.3; small: 0.3 to < 0.5; moderate: 0.5 to < 0.7; and large ≥ 0.7.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Bowel
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Significance level of 0.01
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect size
Estimated Value 0.42
Estimation Comments Minimally important difference (MID) defined as an effect size of at least 0.5. Effect sizes are interpreted as negligible: < 0.3; small: 0.3 to < 0.5; moderate: 0.5 to < 0.7; and large ≥ 0.7.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection EBRT + Brachytherapy, Brachytherapy Only
Comments Sexual
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0072
Comments Significance level of 0.01
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect size
Estimated Value 0.27
Estimation Comments Minimally important difference (MID) defined as an effect size of at least 0.5. Effect sizes are interpreted as negligible: < 0.3; small: 0.3 to < 0.5; moderate: 0.5 to < 0.7; and large ≥ 0.7.
12.Secondary Outcome
Title Change in Health-related Quality of Life From Baseline to 4-Months as Measured by EQ-5D (European Quality of Life-5 Domains) and AUA-SI (American Urological Association-Symptom Index)
Hide Description [Not Specified]
Time Frame Baseline and 4 months after start of radiation
Outcome Measure Data Not Reported
13.Secondary Outcome
Title Change in Health-Related Quality of Life From Baseline to 24-Months as Measured by EQ-5D and AUA-SI
Hide Description [Not Specified]
Time Frame Baseline and 24 months after start of radiation
Outcome Measure Data Not Reported
14.Other Pre-specified Outcome
Title Feasibility of Collecting Medicare Data in a Large RTOG Prostate Cancer Clinical Trial for Cost Effectiveness and Cost Utility Analysis of Combined Treatment With Interstitial Brachytherapy and External Beam Radiotherapy
Hide Description [Not Specified]
Time Frame Analysis occurs after all patients have been potentially followed for 5 years.
Hide Outcome Measure Data
Hide Analysis Population Description
The pilot portion of the trial determined that the data required for this analysis was not able to be obtained, and therefore, there are no results for this outcome measure.
Arm/Group Title EBRT + Brachytherapy Brachytherapy Only
Hide Arm/Group Description:
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
Transperineal interstitial permanent brachytherapy (125/145)
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
Adverse Event Reporting Description Eligible patients who started study treatment are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
 
Arm/Group Title EBRT + Brachytherapy Brachytherapy Only
Hide Arm/Group Description 45 Gy EBRT to the prostate and seminal vesicles (1.8 Gy daily over 5 weeks) followed within 2-4 weeks by transperineal interstitial permanent brachytherapy as 100 Gy Palladium-103 (P-102) or 110 Gy Iodine-125 (I-125) seeds. Transperineal interstitial permanent brachytherapy as 125 Gy Palladium-103 (P-103) or 145 Gy Iodine-125 (I-125) seeds within 4 weeks of study entry.
All-Cause Mortality
EBRT + Brachytherapy Brachytherapy Only
Affected / at Risk (%) Affected / at Risk (%)
Total   46/282 (16.31%)   55/288 (19.10%) 
Show Serious Adverse Events Hide Serious Adverse Events
EBRT + Brachytherapy Brachytherapy Only
Affected / at Risk (%) Affected / at Risk (%)
Total   52/282 (18.44%)   41/288 (14.24%) 
Blood and lymphatic system disorders     
Hemoglobin decreased * 1  1/282 (0.35%)  0/288 (0.00%) 
Cardiac disorders     
Circulatory or cardiac-Other * 1  0/282 (0.00%)  1/288 (0.35%) 
Myocardial ischaemia * 1  1/282 (0.35%)  0/288 (0.00%) 
Supraventricular arrhythmia NOS * 1  1/282 (0.35%)  0/288 (0.00%) 
Gastrointestinal disorders     
Diarrhea NOS * 1  1/282 (0.35%)  0/288 (0.00%) 
GI-other * 1  1/282 (0.35%)  0/288 (0.00%) 
Ileus * 1  0/282 (0.00%)  1/288 (0.35%) 
Late RT Toxicity: Other GI : NOS  2  1/282 (0.35%)  3/288 (1.04%) 
Late RT Toxicity: Small/Large Intestine: NOS  2  6/282 (2.13%)  3/288 (1.04%) 
Melaena * 1  1/282 (0.35%)  0/288 (0.00%) 
Proctitis NOS * 1  0/282 (0.00%)  1/288 (0.35%) 
General disorders     
Late RT Toxicity: Other : NOS  2  14/282 (4.96%)  9/288 (3.13%) 
Infections and infestations     
Infection NOS * 1  1/282 (0.35%)  0/288 (0.00%) 
Metabolism and nutrition disorders     
Hyponatremia * 1  0/282 (0.00%)  1/288 (0.35%) 
Nervous system disorders     
Cerebral ischaemia * 1  1/282 (0.35%)  0/288 (0.00%) 
Headache NOS * 1  1/282 (0.35%)  0/288 (0.00%) 
Renal and urinary disorders     
Dysuria * 1  1/282 (0.35%)  2/288 (0.69%) 
Late RT Toxicity: Bladder/Other GU : NOS  2  22/282 (7.80%)  9/288 (3.13%) 
Renal/GU-Other * 1  0/282 (0.00%)  1/288 (0.35%) 
Ureteric obstruction * 1  0/282 (0.00%)  1/288 (0.35%) 
Urinary frequency * 1  10/282 (3.55%)  7/288 (2.43%) 
Urinary retention * 1  4/282 (1.42%)  4/288 (1.39%) 
Reproductive system and breast disorders     
Impotence * 1  1/282 (0.35%)  6/288 (2.08%) 
1
Term from vocabulary, CTC (2.0)
2
Term from vocabulary, RTOG/EORTC Late Tox.
*
Indicates events were collected by non-systematic assessment
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
EBRT + Brachytherapy Brachytherapy Only
Affected / at Risk (%) Affected / at Risk (%)
Total   220/282 (78.01%)   208/288 (72.22%) 
Gastrointestinal disorders     
Diarrhea NOS * 1  26/282 (9.22%)  6/288 (2.08%) 
Late RT Toxicity: Other GI : NOS  2  78/282 (27.66%)  34/288 (11.81%) 
Late RT Toxicity: Small/Large Intestine: NOS  2  88/282 (31.21%)  37/288 (12.85%) 
General disorders     
Fatigue * 1  25/282 (8.87%)  4/288 (1.39%) 
Late RT Toxicity: Other : NOS  2  121/282 (42.91%)  99/288 (34.38%) 
Renal and urinary disorders     
Dysuria * 1  52/282 (18.44%)  28/288 (9.72%) 
Late RT Toxicity: Bladder/Other GU : NOS  2  160/282 (56.74%)  147/288 (51.04%) 
Urinary frequency * 1  96/282 (34.04%)  88/288 (30.56%) 
Urinary retention * 1  26/282 (9.22%)  36/288 (12.50%) 
1
Term from vocabulary, CTC (2.0)
2
Term from vocabulary, RTOG/EORTC Late Tox.
*
Indicates events were collected by non-systematic assessment
Indicates events were collected by systematic assessment
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
Organization: NRG Oncology
Phone: 215-574-3208
EMail: seiferheldw@nrgoncology.org
Layout table for additonal information
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00063882     History of Changes
Other Study ID Numbers: RTOG 0232
CDR0000288823
NCI-2009-01091 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Submitted: July 8, 2003
First Posted: July 9, 2003
Results First Submitted: May 21, 2019
Results First Posted: October 16, 2019
Last Update Posted: October 16, 2019