Trial Outcomes & Findings for Interstitial Brachytherapy With or Without External-Beam Radiation Therapy in Treating Patients With Prostate Cancer (NCT NCT00063882)
NCT ID: NCT00063882
Last Updated: 2023-03-02
Results Overview
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.
COMPLETED
PHASE3
588 participants
From randomization to 5 years
2023-03-02
Participant Flow
Participant milestones
| Measure |
EBRT + Brachytherapy
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Overall Study
STARTED
|
292
|
296
|
|
Overall Study
Eligible Patients
|
287
|
292
|
|
Overall Study
Has Acute Adverse Event Data
|
282
|
288
|
|
Overall Study
Has Late Adverse Event Data
|
282
|
287
|
|
Overall Study
COMPLETED
|
287
|
292
|
|
Overall Study
NOT COMPLETED
|
5
|
4
|
Reasons for withdrawal
| Measure |
EBRT + Brachytherapy
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Overall Study
Protocol Violation
|
3
|
3
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
Baseline Characteristics
Interstitial Brachytherapy With or Without External-Beam Radiation Therapy in Treating Patients With Prostate Cancer
Baseline characteristics by cohort
| Measure |
EBRT + Brachytherapy
n=287 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=292 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
Total
n=579 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
≤ 59
|
41 Participants
n=5 Participants
|
51 Participants
n=7 Participants
|
92 Participants
n=5 Participants
|
|
Age, Customized
60-69
|
141 Participants
n=5 Participants
|
134 Participants
n=7 Participants
|
275 Participants
n=5 Participants
|
|
Age, Customized
70-79
|
102 Participants
n=5 Participants
|
103 Participants
n=7 Participants
|
205 Participants
n=5 Participants
|
|
Age, Customized
≥ 80
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
287 Participants
n=5 Participants
|
292 Participants
n=7 Participants
|
579 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
274 Participants
n=5 Participants
|
275 Participants
n=7 Participants
|
549 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
50 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
102 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
223 Participants
n=5 Participants
|
226 Participants
n=7 Participants
|
449 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Baseline Prostate Specific Antigen (PSA)
0-<10 ng/ml
|
256 Participants
n=5 Participants
|
261 Participants
n=7 Participants
|
517 Participants
n=5 Participants
|
|
Baseline Prostate Specific Antigen (PSA)
10-20 ng/ml
|
31 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
|
Zubrod Performance Status
0
|
275 Participants
n=5 Participants
|
281 Participants
n=7 Participants
|
556 Participants
n=5 Participants
|
|
Zubrod Performance Status
1
|
12 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Combined Gleason Score (GS)
≤ 6
|
31 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
|
Combined Gleason Score (GS)
7
|
256 Participants
n=5 Participants
|
260 Participants
n=7 Participants
|
516 Participants
n=5 Participants
|
|
Gleason Score & PSA
GS<7 and PSA 10-20
|
31 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
|
Gleason Score & PSA
GS 7 and PSA < 10
|
256 Participants
n=5 Participants
|
260 Participants
n=7 Participants
|
516 Participants
n=5 Participants
|
|
T Stage
T1
|
191 Participants
n=5 Participants
|
195 Participants
n=7 Participants
|
386 Participants
n=5 Participants
|
|
T Stage
T2
|
96 Participants
n=5 Participants
|
97 Participants
n=7 Participants
|
193 Participants
n=5 Participants
|
|
Neoadjuvant Hormone Therapy
Yes
|
22 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
|
Neoadjuvant Hormone Therapy
No
|
265 Participants
n=5 Participants
|
267 Participants
n=7 Participants
|
532 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From randomization to 5 yearsPopulation: All Eligible Patients
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.
Outcome measures
| Measure |
EBRT + Brachytherapy
n=287 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=292 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
5-Year Freedom From Progression Rate
|
85.5 percentage of participants
Interval 81.3 to 89.7
|
83.1 percentage of participants
Interval 78.7 to 87.5
|
SECONDARY outcome
Timeframe: 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.Population: All Eligible Patients
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.
Outcome measures
| Measure |
EBRT + Brachytherapy
n=287 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=292 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Biochemical Failure Rate (Protocol Definition)
|
10.5 percentage of participants
Interval 7.2 to 14.4
|
10.5 percentage of participants
Interval 7.3 to 14.4
|
SECONDARY outcome
Timeframe: 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.Population: All Eligible Patients
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.
Outcome measures
| Measure |
EBRT + Brachytherapy
n=287 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=292 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Biochemical Failure (Phoenix Definition)
|
8.0 percentage of participants
Interval 5.2 to 11.6
|
8.1 percentage of participants
Interval 5.3 to 11.7
|
SECONDARY outcome
Timeframe: 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.Population: All Eligible Patients
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.
Outcome measures
| Measure |
EBRT + Brachytherapy
n=287 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=292 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Prostate Cancer Death
|
0.4 percentage of participants
Interval 0.0 to 1.9
|
1.1 percentage of participants
Interval 0.3 to 2.9
|
SECONDARY outcome
Timeframe: 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.Population: All Eligible Patients
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.
Outcome measures
| Measure |
EBRT + Brachytherapy
n=287 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=292 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Local Failure
|
1.5 percentage of participants
Interval 0.5 to 3.5
|
1.1 percentage of participants
Interval 0.3 to 2.9
|
SECONDARY outcome
Timeframe: 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.Population: All Eligible Patients
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.
Outcome measures
| Measure |
EBRT + Brachytherapy
n=287 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=292 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Distant Metastases
|
2.9 percentage of participants
Interval 1.4 to 5.4
|
2.1 percentage of participants
Interval 0.9 to 4.4
|
SECONDARY outcome
Timeframe: 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.Population: All Eligible Patients
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.
Outcome measures
| Measure |
EBRT + Brachytherapy
n=287 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=292 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Overall Survival
|
95.3 percentage of participants
Interval 92.8 to 97.8
|
93.2 percentage of participants
Interval 90.3 to 96.2
|
SECONDARY outcome
Timeframe: Zero to 180 days from the start of radiationPopulation: Eligible patients who started study treatment
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.
Outcome measures
| Measure |
EBRT + Brachytherapy
n=282 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=288 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Percentage of Patients With Acute Grade 2+ and Grade 3+ Toxicities [Genitourinary (GU), Gastrointestinal (GI), and Overall]
Grade 3+ GU/GI
|
6.0 percentage of participants
Interval 3.7 to 9.5
|
5.6 percentage of participants
Interval 3.4 to 8.9
|
|
Percentage of Patients With Acute Grade 2+ and Grade 3+ Toxicities [Genitourinary (GU), Gastrointestinal (GI), and Overall]
Grade 3+ Overall
|
7.8 percentage of participants
Interval 5.2 to 11.6
|
8.3 percentage of participants
Interval 5.6 to 12.2
|
|
Percentage of Patients With Acute Grade 2+ and Grade 3+ Toxicities [Genitourinary (GU), Gastrointestinal (GI), and Overall]
Grade 2+ GU/GI
|
24.1 percentage of participants
Interval 19.5 to 29.4
|
21.9 percentage of participants
Interval 17.5 to 27.0
|
|
Percentage of Patients With Acute Grade 2+ and Grade 3+ Toxicities [Genitourinary (GU), Gastrointestinal (GI), and Overall]
Grade 2+ Overall
|
27.7 percentage of participants
Interval 22.8 to 33.2
|
26.4 percentage of participants
Interval 21.6 to 31.8
|
SECONDARY outcome
Timeframe: From 181 days after the start of radiation to last follow-up. Maximum follow-up at time of analysis was 13.9 years.Population: Eligible patients who started study treatment and had follow-up data \> 180 days from the start of treatment
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.
Outcome measures
| Measure |
EBRT + Brachytherapy
n=282 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=287 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Time to Late Grade 3+ Toxicities [Genitourinary (GU), Gastrointestinal (GI), and Overall]
Grade 3+ GU/GI
|
7.9 percentage of participants
Interval 5.1 to 11.4
|
3.8 percentage of participants
Interval 2.0 to 6.5
|
|
Time to Late Grade 3+ Toxicities [Genitourinary (GU), Gastrointestinal (GI), and Overall]
Grade 3+ Overall
|
10.4 percentage of participants
Interval 7.2 to 14.3
|
6.6 percentage of participants
Interval 4.1 to 9.9
|
SECONDARY outcome
Timeframe: Baseline and 4 months after start of radiationPopulation: Eligible patients with baseline and 4-month EPIC data
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.
Outcome measures
| Measure |
EBRT + Brachytherapy
n=222 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=241 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Change in Expanded Prostate Cancer Index Composite (EPIC) From Baseline to 4 Months
Urinary
|
-20.1 units on a scale
Standard Deviation 15.4
|
-14.1 units on a scale
Standard Deviation 14.8
|
|
Change in Expanded Prostate Cancer Index Composite (EPIC) From Baseline to 4 Months
Urinary-Incontinence
|
-10.3 units on a scale
Standard Deviation 17.7
|
-8.7 units on a scale
Standard Deviation 17.7
|
|
Change in Expanded Prostate Cancer Index Composite (EPIC) From Baseline to 4 Months
Urinary-Irritative
|
-23.6 units on a scale
Standard Deviation 18.1
|
-15.9 units on a scale
Standard Deviation 17.3
|
|
Change in Expanded Prostate Cancer Index Composite (EPIC) From Baseline to 4 Months
Bowel
|
-10.4 units on a scale
Standard Deviation 13.6
|
-6.3 units on a scale
Standard Deviation 12.7
|
|
Change in Expanded Prostate Cancer Index Composite (EPIC) From Baseline to 4 Months
Sexual
|
-13.7 units on a scale
Standard Deviation 22.3
|
-11.2 units on a scale
Standard Deviation 21.0
|
SECONDARY outcome
Timeframe: Baseline and 24 months after start of radiationPopulation: Eligible patients with baseline and 24-month EPIC data
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.
Outcome measures
| Measure |
EBRT + Brachytherapy
n=201 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=219 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Change in Expanded Prostate Cancer Index Composite (EPIC) From Baseline to 24 Months
Urinary
|
-11.2 units on a scale
Standard Deviation 15.7
|
-5.6 units on a scale
Standard Deviation 13.6
|
|
Change in Expanded Prostate Cancer Index Composite (EPIC) From Baseline to 24 Months
Urinary- Incontinence
|
-7.6 units on a scale
Standard Deviation 17.7
|
-6.3 units on a scale
Standard Deviation 15.5
|
|
Change in Expanded Prostate Cancer Index Composite (EPIC) From Baseline to 24 Months
Urinary-Irritative
|
-11.9 units on a scale
Standard Deviation 17.4
|
-4.8 units on a scale
Standard Deviation 14.3
|
|
Change in Expanded Prostate Cancer Index Composite (EPIC) From Baseline to 24 Months
Bowel
|
-7.1 units on a scale
Standard Deviation 12.6
|
-2.4 units on a scale
Standard Deviation 9.9
|
|
Change in Expanded Prostate Cancer Index Composite (EPIC) From Baseline to 24 Months
Sexual
|
-16.7 units on a scale
Standard Deviation 23.4
|
-10.6 units on a scale
Standard Deviation 21.0
|
SECONDARY outcome
Timeframe: Baseline and 4 months after start of radiationPopulation: Eligible patients who had a total AUA-SI score at baseline and 4 months
The AUA-SI is a validated 7-item measure used to assess urinary symptoms. A higher score indicates more severe symptoms for the individual questions and overall total. Six questions ask about frequency of symptoms over the past month with possible responses: 0= Not at all; 1 = Less than 1 time in 5; 2 = less than half the time, 3 = About half the time, 4 = More than half the time, 5 = Almost always. An additional question asks the number of times one gets up to urinate after going to bed, with response indicating the exact number of times ranging from 0 to 5. The total score is the sum of the questions and ranges from 0 to 35. Change is calculated as follow-up timepoint score - baseline score such that a negative change reflects an improvement at the follow-up timepoint and a positive change reflects a decline at the follow-up timepoint.
Outcome measures
| Measure |
EBRT + Brachytherapy
n=287 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=292 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Change in Total American Urological Association Symptom Index (AUA-SI) Score From Baseline to 4 Months
|
10.12 units on a scale
Standard Deviation 7.94
|
7.77 units on a scale
Standard Deviation 7.44
|
SECONDARY outcome
Timeframe: Baseline and 24 months after start of radiationPopulation: Eligible patients who had a total AUA-SI score at baseline and 24 months.
The AUA-SI is a validated 7-item measure used to assess urinary symptoms. A higher score indicates more severe symptoms for the individual questions and overall total. Six questions ask about frequency of symptoms over the past month with possible responses: 0= Not at all; 1 = Less than 1 time in 5; 2 = less than half the time, 3 = About half the time, 4 = More than half the time, 5 = Almost always. An additional question asks the number of times one gets up to urinate after going to bed, with response indicating the exact number of times ranging from 0 to 5. The total score is the sum of the questions and ranges from 0 to 35. Change is calculated as follow-up timepoint score - baseline score such that a negative change reflects an improvement at the follow-up timepoint and a positive change reflects a decline at the follow-up timepoint.
Outcome measures
| Measure |
EBRT + Brachytherapy
n=223 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=234 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Change in Total American Urological Association Symptom Index (AUA-SI) Score From Baseline to 24 Months
|
4.54 units on a scale
Standard Deviation 6.94
|
2.37 units on a scale
Standard Deviation 6.05
|
SECONDARY outcome
Timeframe: Baseline and 4 months after start of radiationPopulation: Questionnaires were not completed by all eligible participants. 218 and 227 EBRT + Brachytherapy participants had VAS and index score data, respectively, at baseline and 4 months; 237 and 248 Brachytherapy Only participants had VAS and index score data, respectively, at baseline and 4 months.
The EQ-5D is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The change score was calculated as the value at the follow-up timepoint minus the value at baseline. A negative change reflects a decline at the follow-up timepoint and a positive change reflects an improvement at the follow-up timepoint.
Outcome measures
| Measure |
EBRT + Brachytherapy
n=287 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=292 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Change in European Quality of Life-5 Domains (EQ-5D) From Baseline to 4 Months
VAS Score
|
-2.71 units on a scale
Standard Deviation 20.26
|
-0.44 units on a scale
Standard Deviation 17.10
|
|
Change in European Quality of Life-5 Domains (EQ-5D) From Baseline to 4 Months
Index Score
|
-0.01 units on a scale
Standard Deviation 0.11
|
-0.01 units on a scale
Standard Deviation 0.12
|
SECONDARY outcome
Timeframe: Baseline and 24 months after start of radiationPopulation: Questionnaires were not completed by all eligible participants. 210 and 212 EBRT + Brachytherapy participants had VAS and index score data, respectively, at baseline and 24 months; 212 and 226 Brachytherapy Only participants had VAS and index score data, respectively, at baseline and 24 months.
The EQ5D is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The change score was calculated as the value at the follow-up timepoint minus the value at baseline. A negative change reflects a decline at the follow-up timepoint and a positive change reflects an improvement at the follow-up timepoint.
Outcome measures
| Measure |
EBRT + Brachytherapy
n=287 Participants
External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)
|
Brachytherapy Only
n=292 Participants
Transperineal interstitial permanent brachytherapy (125/145)
|
|---|---|---|
|
Change in European Quality of Life-5 Domains (EQ-5D) From Baseline to 24 Months
VAS Score
|
-0.28 units on a scale
Standard Deviation 17.56
|
-0.57 units on a scale
Standard Deviation 14.94
|
|
Change in European Quality of Life-5 Domains (EQ-5D) From Baseline to 24 Months
Index Score
|
-0.02 units on a scale
Standard Deviation 0.12
|
-0.01 units on a scale
Standard Deviation 0.12
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Analysis occurs after all patients have been potentially followed for 5 years.Population: 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.
Outcome measures
Outcome data not reported
Adverse Events
EBRT + Brachytherapy
Brachytherapy Only
Serious adverse events
| Measure |
EBRT + Brachytherapy
n=282 participants at risk
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.
|
Brachytherapy Only
n=288 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
0.35%
1/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.00%
0/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Cardiac disorders
Circulatory or cardiac-Other
|
0.00%
0/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.35%
1/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Cardiac disorders
Myocardial ischaemia
|
0.35%
1/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.00%
0/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Cardiac disorders
Supraventricular arrhythmia NOS
|
0.35%
1/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.00%
0/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Gastrointestinal disorders
Diarrhea NOS
|
0.35%
1/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.00%
0/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Gastrointestinal disorders
GI-other
|
0.35%
1/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.00%
0/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.35%
1/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Gastrointestinal disorders
Late RT Toxicity: Other GI : NOS
|
0.35%
1/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
1.0%
3/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Gastrointestinal disorders
Late RT Toxicity: Small/Large Intestine: NOS
|
2.1%
6/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
1.0%
3/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Gastrointestinal disorders
Melaena
|
0.35%
1/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.00%
0/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Gastrointestinal disorders
Proctitis NOS
|
0.00%
0/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.35%
1/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
General disorders
Late RT Toxicity: Other : NOS
|
5.0%
14/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
3.1%
9/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Infections and infestations
Infection NOS
|
0.35%
1/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.00%
0/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.35%
1/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Nervous system disorders
Cerebral ischaemia
|
0.35%
1/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.00%
0/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Nervous system disorders
Headache NOS
|
0.35%
1/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.00%
0/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Renal and urinary disorders
Dysuria
|
0.35%
1/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.69%
2/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Renal and urinary disorders
Late RT Toxicity: Bladder/Other GU : NOS
|
7.8%
22/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
3.1%
9/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Renal and urinary disorders
Renal/GU-Other
|
0.00%
0/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.35%
1/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Renal and urinary disorders
Ureteric obstruction
|
0.00%
0/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
0.35%
1/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Renal and urinary disorders
Urinary frequency
|
3.5%
10/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
2.4%
7/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Renal and urinary disorders
Urinary retention
|
1.4%
4/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
1.4%
4/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Reproductive system and breast disorders
Impotence
|
0.35%
1/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
2.1%
6/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
Other adverse events
| Measure |
EBRT + Brachytherapy
n=282 participants at risk
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.
|
Brachytherapy Only
n=288 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea NOS
|
9.2%
26/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
2.1%
6/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Gastrointestinal disorders
Late RT Toxicity: Other GI : NOS
|
27.7%
78/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
11.8%
34/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Gastrointestinal disorders
Late RT Toxicity: Small/Large Intestine: NOS
|
31.2%
88/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
12.8%
37/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
General disorders
Fatigue
|
8.9%
25/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
1.4%
4/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
General disorders
Late RT Toxicity: Other : NOS
|
42.9%
121/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
34.4%
99/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Renal and urinary disorders
Dysuria
|
18.4%
52/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
9.7%
28/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Renal and urinary disorders
Late RT Toxicity: Bladder/Other GU : NOS
|
56.7%
160/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
51.0%
147/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Renal and urinary disorders
Urinary frequency
|
34.0%
96/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
30.6%
88/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
|
Renal and urinary disorders
Urinary retention
|
9.2%
26/282 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
12.5%
36/288 • From randomization to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
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.
|
Additional Information
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