Interstitial Brachytherapy With or Without External-Beam Radiation Therapy in Treating Patients With Prostate Cancer

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT00063882
• Collaborator: National Cancer Institute (NCI) (NIH), NRG Oncology (Other)
• Enrollment: 588
• Locations: 170
• Arms: 2
• Patients Per Site: 3.5

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays and other sources to damage tumor cells. Interstitial brachytherapy uses radioactive material placed directly into or near a tumor to kill tumor cells. Combining interstitial brachytherapy with external-beam radiation therapy may kill more tumor cells. It is not yet known whether interstitial brachytherapy is more effective with or without external-beam radiation therapy in treating prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of interstitial brachytherapy with or without external-beam radiation therapy in treating patients who have prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Radiation: Brachytherapy (100/110); Radiation: Brachytherapy (125/145); Radiation: External Beam Radiation Therapy	Phase 3

Detailed Description

OBJECTIVES:

• Compare the 5-year freedom from progression in patients with intermediate-risk prostate cancer treated with interstitial brachytherapy with or without external beam radiotherapy (EBRT).

• Compare biochemical (i.e., prostate-specific antigen) failure, biochemical failure by the Phoenix definition, disease-specific survival, local progression, and distant metastases in patients treated with these regimens.

• Compare morbidity and quality of life of patients treated with these regimens.

• Determine the feasibility of collecting Medicare data in a large Radiation Therapy Oncology Group (RTOG) prostate cancer clinical trial for cost effectiveness and cost utility analysis of combined treatment with interstitial brachytherapy and EBRT.

• Prospectively collect diagnostic biopsy samples from these patients for future biomarker analyses.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease stage (T1c vs T2a or T2b), Gleason score (≤ 6 vs 7), prostate-specific antigen (< 10 ng/mL vs 10-20 ng/mL), and prior neoadjuvant hormonal therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo external beam radiotherapy 5 days a week for 5 weeks. Within 2-4 weeks of radiotherapy, patients undergo interstitial brachytherapy with iodine I 125 or palladium Pd 103 seeds.

• Arm II: Patients undergo interstitial brachytherapy only, as in arm I. Quality of life is assessed at baseline, at 4, 12, and 24 months, and then annually for 3 years.

After completion of study treatment, patients are followed at 3-5 weeks, at 4, 6, 9, and 12 months, every 6 months for 4 years, and then annually thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 588 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy With Brachytherapy Alone for Selected Patients With Intermediate Risk Prostatic Carcinoma
• Study Start Date: Jun 1, 2003
• Actual Primary Completion Date: May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EBRT + Brachytherapy External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)	Radiation: Brachytherapy (100/110); 100 Gy Palladium-103 (P-102) or 110 Gy Iodine-125 (I-125) seeds within 2-4 weeks of completion of external beam radiotherapy.; Radiation: External Beam Radiation Therapy; Total dose of 45 Gy to the prostate and seminal vesicles as a daily dose of 1.8 Gy given 5 times per week. The prescribed dose is defined at the International Commission of Radiation Units and Measurements (ICRU) reference point. Both 3D-conformal radiation therapy (3DCRT) and intensity modulated radiation therapy (IMRT) are permitted.; Other Names: EBRT
Active Comparator: Brachytherapy Only Transperineal interstitial permanent brachytherapy (125/145)	Radiation: Brachytherapy (125/145); 125 Gy Palladium-103 (P-103) or 145 Gy Iodine-125 (I-125) seeds within 4 weeks of study entry.

Outcome Measures

Primary Outcome Measures

1. 5-Year Freedom From Progression Rate [From randomization to 5 years]

   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.

Secondary Outcome Measures

1. Biochemical Failure Rate (Protocol Definition) [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.]

   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.

2. Biochemical Failure (Phoenix Definition) [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.]

   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.

3. Prostate Cancer Death [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.]

   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.

4. Local Failure [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.]

   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.

5. Distant Metastases [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.]

   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.

6. Overall Survival [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.]

   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.

7. Percentage of Patients With Acute Grade 2+ and Grade 3+ Toxicities [Genitourinary (GU), Gastrointestinal (GI), and Overall] [Zero to 180 days from the start of radiation]

   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.

8. Time to Late Grade 3+ Toxicities [Genitourinary (GU), Gastrointestinal (GI), and Overall] [From 181 days after the start of radiation to last follow-up. Maximum follow-up at time of analysis was 13.9 years.]

   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.

9. Change in Health-related Quality of Life From Baseline to 4-Months as Measured by Expanded Prostate Cancer Index Composite (EPIC) [Baseline and 4 months after start of radiation]

   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.

10. Change in Health-Related Quality of Life From Baseline to 24-Months as Measured by EPIC [Baseline and 24 months after start of radiation]

    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.

11. 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) [Baseline and 4 months after start of radiation]

12. Change in Health-Related Quality of Life From Baseline to 24-Months as Measured by EQ-5D and AUA-SI [Baseline and 24 months after start of radiation]

Other Outcome Measures

1. 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 [Analysis occurs after all patients have been potentially followed for 5 years.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

• T1c-T2b, N0, M0

• Intermediate-risk disease, as defined by 1 of the following:

• Gleason score < 7 AND prostate-specific antigen (PSA) 10-20 ng/mL

• Gleason score 7 AND PSA < 10 ng/mL

• No evidence of distant metastases

• Prostate volume ≤ 60 cc by transrectal ultrasonography

• American Urological Association voiding symptom score no greater than 15 (alpha blockers allowed)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Patients must use effective contraception

• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ at any other site

• No major medical or psychiatric illness that would preclude study therapy

• No hip prosthesis

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Prior neoadjuvant hormonal therapy allowed provided the following are true:

• Therapy was initiated within 2-6 months of study enrollment

• Therapy was no more than 6 months in duration

• Use of 5-alpha reductase inhibitors (e.g., finasteride) is discontinued before registration

• No concurrent hormonal therapy

Radiotherapy

• No prior pelvic radiotherapy

Surgery

• No prior radical surgery for prostate cancer

• No prior transurethral resection of the prostate

• No prior cryosurgery

Other

• No prior transurethral needle ablation of the prostate

• No prior transurethral microwave thermotherapy of the prostate

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Services Foundation	Phoenix	Arizona	United States	85013
2	Auburn Radiation Oncology	Auburn	California	United States	95603
3	Alta Bates Summit Comprehensive Cancer Center	Berkeley	California	United States	94704
4	Peninsula Medical Center	Burlingame	California	United States	94010
5	Radiation Oncology Centers - Cameron Park	Cameron Park	California	United States	95682
6	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California	United States	95608
7	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
8	Valley Medical Oncology Consultants - Castro Valley	Castro Valley	California	United States	94546
9	Valley Medical Oncology	Fremont	California	United States	94538
10	California Cancer Center - Woodward Park Office	Fresno	California	United States	93720
11	Kaiser Permanente Medical Center - Hayward	Hayward	California	United States	94545
12	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
13	El Camino Hospital Cancer Center	Mountain View	California	United States	94040
14	Sutter Health - Western Division Cancer Research Group	Novato	California	United States	94945
15	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
16	Bay Area Breast Surgeons, Incorporated	Oakland	California	United States	94609
17	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609
18	Larry G Strieff MD Medical Corporation	Oakland	California	United States	94609
19	Tom K Lee, Incorporated	Oakland	California	United States	94609
20	Kaiser Permanente - Division of Research - Oakland	Oakland	California	United States	94611
21	Kaiser Permanente Medical Center - Oakland	Oakland	California	United States	94611
22	Kaiser Permanente Medical Center - Rancho Cordova	Rancho Cordova	California	United States	95670
23	Kaiser Permanente Medical Center - Redwood City	Redwood City	California	United States	94063
24	Kaiser Permanente Medical Center - Richmond	Richmond	California	United States	94801
25	Rohnert Park Cancer Center	Rohnert Park	California	United States	94928
26	Kaiser Permanente Medical Center - Roseville	Roseville	California	United States	95661
27	Radiation Oncology Center - Roseville	Roseville	California	United States	95661
28	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California	United States	95815
29	Mercy General Hospital	Sacramento	California	United States	95819
30	South Sacramento Cancer Center	Sacramento	California	United States	95823
31	South Sacramento Kaiser-Permanente Medical Center	Sacramento	California	United States	95823
32	Kaiser Permanente Medical Center - Sacramento	Sacramento	California	United States	95825
33	Kaiser Permanente Medical Center - San Francisco Geary Campus	San Francisco	California	United States	94115
34	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
35	California Pacific Medical Center - California Campus	San Francisco	California	United States	94118
36	Kaiser Permanente Medical Center - Santa Teresa	San Jose	California	United States	95119
37	Kaiser Foundation Hospital - San Rafael	San Rafael	California	United States	94903
38	Kaiser Permanente Medical Center - Santa Clara Kiely Campus	Santa Clara	California	United States	95051
39		Santa Clara	California	United States	95051
40	Kaiser Permanente Medical Center - Santa Rosa	Santa Rosa	California	United States	95403
41	Kaiser Permanente Medical Center - South San Francisco	South San Francisco	California	United States	94080
42	Kaiser Permanente Medical Facility - Stockton	Stockton	California	United States	95210
43	Solano Radiation Oncology Center	Vacaville	California	United States	95687
44	Sutter Solano Medical Center	Vallejo	California	United States	94589
45	Kaiser Permanente Medical Center - Walnut Creek	Walnut Creek	California	United States	94596
46	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
47	Hospital of Saint Raphael	New Haven	Connecticut	United States	06511
48	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
49	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
50	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
51	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida	United States	33458
52	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
53	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
54	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
55	Cancer Institute at St. John's Hospital	Springfield	Illinois	United States	62702
56	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
57	Menorah Medical Center	Overland Park	Kansas	United States	66209
58	CCOP - Kansas City	Prairie Village	Kansas	United States	66208
59	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
60	St. Agnes Hospital Cancer Center	Baltimore	Maryland	United States	21229
61	Cape Cod Hospital	Hyannis	Massachusetts	United States	02601
62	Shields Radiation Oncology Center - Mansfield	Mansfield	Massachusetts	United States	02048
63	South Suburban Oncology Center	Quincy	Massachusetts	United States	02169
64	Winchester Hospital Radiation Oncology Center	Winchester	Massachusetts	United States	01890
65	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
66	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
67	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
68	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
69	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
70	Hurley Medical Center	Flint	Michigan	United States	48503
71	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
72	Foote Memorial Hospital	Jackson	Michigan	United States	49201
73	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
74	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
75	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
76	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
77	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
78	St. John Macomb Hospital	Warren	Michigan	United States	48093
79	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
80	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri	United States	64111
81	St. Joseph Medical Center	Kansas City	Missouri	United States	64114
82	North Kansas City Hospital	Kansas City	Missouri	United States	64116
83	Parvin Radiation Oncology	Kansas City	Missouri	United States	64116
84	Research Medical Center	Kansas City	Missouri	United States	64132
85	Liberty Hospital	Liberty	Missouri	United States	64068
86	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
87	Saint Joseph Oncology, Incorporated	Saint Joseph	Missouri	United States	64507
88	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri	United States	63110
89	Barnes-Jewish West County Hospital	Saint Louis	Missouri	United States	63141
90	Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - St. Peters	Saint Peters	Missouri	United States	63376
91	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
92	Nevada Cancer Institute	Las Vegas	Nevada	United States	89135
93	Renown Institute for Cancer at Renown Regional Medical Center	Reno	Nevada	United States	89502
94	Kingsbury Center for Cancer Care at Cheshire Medical Center	Keene	New Hampshire	United States	03431
95	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
96	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey	United States	08053
97	Fox Chase Virtua Health Cancer Program at Virtua West Jersey	Voorhees	New Jersey	United States	08043
98	New York Methodist Hospital	Brooklyn	New York	United States	11215
99	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
100	Sands Cancer Center	Canandaigua	New York	United States	14424
101	Beth Israel Medical Center - Petrie Division	New York	New York	United States	10003-3803
102	Highland Hospital of Rochester	Rochester	New York	United States	14620
103	University Radiation Oncology at Parkridge Hospital	Rochester	New York	United States	14626
104	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
105	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
106	Coleman Radiation Oncology Center at Carter General Hospital	Morehead City	North Carolina	United States	28557
107	CarolinaEast Cancer Care	New Bern	North Carolina	United States	28560
108	South Atlantic Radiation Oncology, LLC	Supply	North Carolina	United States	28462
109	Coastal Carolina Radiation Oncology Center	Wilmington	North Carolina	United States	28401
110	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
111	Radiation Oncology Center	Alliance	Ohio	United States	44601
112	Barberton Citizens Hospital	Barberton	Ohio	United States	44203
113	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
114	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210-1240
115	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
116	CCOP - Columbus	Columbus	Ohio	United States	43215
117	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
118	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
119	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
120	Grady Memorial Hospital	Delaware	Ohio	United States	43015
121	Community Cancer Center	Elyria	Ohio	United States	44035
122	Hematology Oncology Center	Elyria	Ohio	United States	44035
123	Lima Memorial Hospital	Lima	Ohio	United States	45804
124	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
125	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537-1839
126	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
127	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
128	Cancer Care Center, Incorporated	Salem	Ohio	United States	44460
129	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
130	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
131	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
132	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
133	Toledo Hospital	Toledo	Ohio	United States	43606
134	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
135	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
136	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
137	St. Anne Mercy Hospital	Toledo	Ohio	United States	43623
138	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
139	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
140	Cancer Treatment Center	Wooster	Ohio	United States	44691
141	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
142	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
143	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania	United States	19111-2497
144	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania	United States	19612-6052
145	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
146	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania	United States	17405
147	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
148	Sandra L. Maxwell Cancer Center	Cedar City	Utah	United States	84720
149	Logan Regional Hospital	Logan	Utah	United States	84321
150	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah	United States	84157
151	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah	United States	84403
152	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
153	Dixie Regional Medical Center - East Campus	Saint George	Utah	United States	84770
154	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah	United States	84106
155	LDS Hospital	Salt Lake City	Utah	United States	84143
156	Norris Cotton Cancer Center - North	Saint Johnsbury	Vermont	United States	05819
157	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
158	Veterans Affairs Medical Center - Richmond	Richmond	Virginia	United States	23249
159	St. Francis Hospital	Federal Way	Washington	United States	98003
160	Good Samaritan Cancer Center	Puyallup	Washington	United States	98372
161	Franciscan Cancer Center at St. Joseph Medical Center	Tacoma	Washington	United States	98405-3004
162	CCOP - Northwest	Tacoma	Washington	United States	98405
163	MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	Washington	United States	98405
164	Columbia Saint Mary's Hospital - Ozaukee	Mequon	Wisconsin	United States	53097
165	Columbia-Saint Mary's Cancer Care Center	Milwaukee	Wisconsin	United States	53211
166	Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
167	All Saints Cancer Center at Wheaton Franciscan Healthcare	Racine	Wisconsin	United States	53405
168	West Allis Memorial Hospital	West Allis	Wisconsin	United States	53227
169	Cross Cancer Institute at University of Alberta	Edmonton	Alberta	Canada	T6G 1Z2
170	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9

Sponsors and Collaborators

• Radiation Therapy Oncology Group
• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: Bradley R. Prestidge, MD, Bon Secours Cancer Institute

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Dec 17, 2014

More Information

Publications

None provided.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00063882
• Other Study ID Numbers: RTOG 0232; CDR0000288823; NCI-2009-01091
• First Posted: Jul 9, 2003
• Last Update Posted: Nov 5, 2021
• Last Verified: Jul 1, 2019

• Keywords provided by Radiation Therapy Oncology Group: stage IIB prostate cancer; stage IIA prostate cancer; adenocarcinoma of the prostate
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Arm/Group Title	EBRT + Brachytherapy	Brachytherapy Only
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	282	288
Has Late Adverse Event Data	282	287
Has Baseline/4-month EPIC Data	222	241
Has Baseline/24-month EPIC Data	201	219
Eligible Patients	287	292
COMPLETED	287	292
NOT COMPLETED	5	4

Baseline Characteristics

Arm/Group Title	EBRT + Brachytherapy	Brachytherapy Only	Total
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 Participants	287	292	579
Age, Customized (Count of 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%	4 1.4%	7 1.2%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	287 100%	292 100%	579 100%
Ethnicity (NIH/OMB) (Count of 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%	7 2.4%	10 1.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 1%	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%
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%	2 0.3%
Unknown or Not Reported	4 1.4%	1 0.3%	5 0.9%
Baseline Prostate Specific Antigen (PSA) (Count of 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%
Zubrod Performance Status (Count of Participants)
0	275 95.8%	281 96.2%	556 96%
1	12 4.2%	11 3.8%	23 4%
Combined Gleason Score (GS) (Count of Participants)
≤ 6	31 10.8%	32 11%	63 10.9%
7	256 89.2%	260 89%	516 89.1%
Gleason Score & PSA (Count of Participants)
GS<7 and PSA 10-20	31 10.8%	32 11%	63 10.9%
GS 7 and PSA < 10	256 89.2%	260 89%	516 89.1%
T Stage (Count of Participants)
T1	191 66.6%	195 66.8%	386 66.7%
T2	96 33.4%	97 33.2%	193 33.3%
Neoadjuvant Hormone Therapy (Count of Participants)
Yes	22 7.7%	25 8.6%	47 8.1%
No	265 92.3%	267 91.4%	532 91.9%

Outcome Measures

1. Primary Outcome

Title	5-Year Freedom From Progression Rate
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

Outcome Measure Data

Analysis Population Description

All Eligible Patients

Arm/Group Title	EBRT + Brachytherapy	Brachytherapy Only
Arm/Group Description	External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)	Transperineal interstitial permanent brachytherapy (125/145)
Measure Participants	287	292
Number (95% Confidence Interval) [percentage of participants]	85.5 29.8%	83.1 28.5%

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
Statistical Test of Hypothesis	p-Value	0.21
	Comments	One-sided significance level of 0.025
	Method	Greenwood's T
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.60 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Brachytherapy only

2. Secondary Outcome

Title	Biochemical Failure Rate (Protocol Definition)
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.

Outcome Measure Data

Analysis Population Description

All Eligible Patients

Arm/Group Title	EBRT + Brachytherapy	Brachytherapy Only
Arm/Group Description	External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)	Transperineal interstitial permanent brachytherapy (125/145)
Measure Participants	287	292
Number (95% Confidence Interval) [percentage of participants]	10.5 3.7%	10.5 3.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments	One-sided significance level of 0.025
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.63 to 1.54
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Brachytherapy Only

3. Secondary Outcome

Title	Biochemical Failure (Phoenix Definition)
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.

Outcome Measure Data

Analysis Population Description

All Eligible Patients

Arm/Group Title	EBRT + Brachytherapy	Brachytherapy Only
Arm/Group Description	External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)	Transperineal interstitial permanent brachytherapy (125/145)
Measure Participants	287	292
Number (95% Confidence Interval) [percentage of participants]	8.0 2.8%	8.1 2.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.97
	Comments	One-sided significance level of 0.025
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.64 to 1.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Brachytherapy Only

4. Secondary Outcome

Title	Prostate Cancer Death
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.

Outcome Measure Data

Analysis Population Description

All Eligible Patients

Arm/Group Title	EBRT + Brachytherapy	Brachytherapy Only
Arm/Group Description	External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)	Transperineal interstitial permanent brachytherapy (125/145)
Measure Participants	287	292
Number (95% Confidence Interval) [percentage of participants]	0.4 0.1%	1.1 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments	One-sided significance level of 0.025
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.36 to 3.90
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Brachytherapy Only

5. Secondary Outcome

Title	Local Failure
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.

Outcome Measure Data

Analysis Population Description

All Eligible Patients

Arm/Group Title	EBRT + Brachytherapy	Brachytherapy Only
Arm/Group Description	External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)	Transperineal interstitial permanent brachytherapy (125/145)
Measure Participants	287	292
Number (95% Confidence Interval) [percentage of participants]	1.5 0.5%	1.1 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.99
	Comments	One-sided significance level of 0.025
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.33 to 3.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Brachytherapy Only

6. Secondary Outcome

Title	Distant Metastases
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.

Outcome Measure Data

Analysis Population Description

All Eligible Patients

Arm/Group Title	EBRT + Brachytherapy	Brachytherapy Only
Arm/Group Description	External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)	Transperineal interstitial permanent brachytherapy (125/145)
Measure Participants	287	292
Number (95% Confidence Interval) [percentage of participants]	2.9 1%	2.1 0.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.81
	Comments	One-sided significance level of 0.025
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; 0.46 to 2.76
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Brachytherapy Only

7. Secondary Outcome

Title	Overall Survival
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.

Outcome Measure Data

Analysis Population Description

All Eligible Patients

Arm/Group Title	EBRT + Brachytherapy	Brachytherapy Only
Arm/Group Description	External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)	Transperineal interstitial permanent brachytherapy (125/145)
Measure Participants	287	292
Number (95% Confidence Interval) [percentage of participants]	95.3 33.2%	93.2 31.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments	One-sided significance level of 0.025
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.51 to 1.17
	Parameter Dispersion	Type: Value:
	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]
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

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment

Arm/Group Title	EBRT + Brachytherapy	Brachytherapy Only
Arm/Group Description	External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)	Transperineal interstitial permanent brachytherapy (125/145)
Measure Participants	282	288
Grade 2+ GU/GI	24.1 8.4%	21.9 7.5%
Grade 2+ Overall	27.7 9.7%	26.4 9%
Grade 3+ GU/GI	6.0 2.1%	5.6 1.9%
Grade 3+ Overall	7.8 2.7%	8.3 2.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Grade 2+ GU/GI
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments	One-sided significance level of 0.05
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.76 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Brachytherapy Only

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Grade 2+ Overall
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.73
	Comments	One-sided significance level of 0.05
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.53
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Brachytherapy Only

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Grade 3+ GU/GI
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.81
	Comments	One-sided significance level of 0.05
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 95%; 0.54 to 2.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Brachytherapy Only

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Grade 3+ Overall
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.82
	Comments	One-sided significance level of 0.05
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.51 to 1.69
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Brachytherapy Only

9. Secondary Outcome

Title	Time to Late Grade 3+ Toxicities [Genitourinary (GU), Gastrointestinal (GI), and Overall]
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.

Outcome Measure Data

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
Arm/Group Description	External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)	Transperineal interstitial permanent brachytherapy (125/145)
Measure Participants	282	287
Grade 3+ GU/GI	7.9 2.8%	3.8 1.3%
Grade 3+ Overall	10.4 3.6%	6.6 2.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Grade 3+ GU/GI
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments	One-sided significance level of 0.025
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.37
	Confidence Interval	(2-Sided) 95%; 1.20 to 4.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Brachytherapy Only

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Grade 3+ Overall
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.029
	Comments	One-sided significance level of 0.025
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.81
	Confidence Interval	(2-Sided) 95%; 1.06 to 3.10
	Parameter Dispersion	Type: Value:
	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)
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

Outcome Measure Data

Analysis Population Description

Eligible patients with baseline and 4-month EPIC data

Arm/Group Title	EBRT + Brachytherapy	Brachytherapy Only
Arm/Group Description	External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)	Transperineal interstitial permanent brachytherapy (125/145)
Measure Participants	222	241
Urinary	-20.1 (15.4)	-14.1 (14.8)
Urinary-Incontinence	-10.3 (17.7)	-8.7 (17.7)
Urinary-Irritative	-23.6 (18.1)	-15.9 (17.3)
Bowel	-10.4 (13.6)	-6.3 (12.7)
Sexual	-13.7 (22.3)	-11.2 (21.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Urinary
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.01
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Effect size
	Estimated Value	0.40
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Urinary- Incontinence
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments	significance level of 0.01
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Effect size
	Estimated Value	0.09
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	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.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Urinary-Irritative
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	significance level of 0.01
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Effect size
	Estimated Value	0.44
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	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.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Bowel
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	significance level of 0.01
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Effect size
	Estimated Value	0.31
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	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.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Sexual
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Effect size
	Estimated Value	0.12
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments
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
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

Outcome Measure Data

Analysis Population Description

Eligible patients with baseline and 24-month EPIC data

Arm/Group Title	EBRT + Brachytherapy	Brachytherapy Only
Arm/Group Description	External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)	Transperineal interstitial permanent brachytherapy (125/145)
Measure Participants	201	219
Urinary	-11.2 (15.7)	-5.6 (13.6)
Urinary- Incontinence	-7.6 (17.7)	-6.3 (15.5)
Urinary-Irritative	-11.9 (17.4)	-4.8 (14.3)
Bowel	-7.1 (12.6)	-2.4 (9.9)
Sexual	-16.7 (23.4)	-10.6 (21.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Urinary
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	Significance level of 0.01
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Effect size
	Estimated Value	0.38
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Urinary-Incontinence
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments	Significance level of 0.01
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Effect size
	Estimated Value	0.08
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	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.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Urinary-Irritative
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.01
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Effect size
	Estimated Value	0.44
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	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.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Bowel
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.01
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Effect size
	Estimated Value	0.42
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	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.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	EBRT + Brachytherapy, Brachytherapy Only
	Comments	Sexual
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0072
	Comments	Significance level of 0.01
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Effect size
	Estimated Value	0.27
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	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)
Time Frame	Baseline and 4 months after start of radiation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Secondary Outcome

Title	Change in Health-Related Quality of Life From Baseline to 24-Months as Measured by EQ-5D and AUA-SI
Time Frame	Baseline and 24 months after start of radiation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

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
Time Frame	Analysis occurs after all patients have been potentially followed for 5 years.

Outcome Measure Data

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
Arm/Group Description	External beam radiation therapy (EBRT) and transperineal interstitial permanent brachytherapy (100/110)	Transperineal interstitial permanent brachytherapy (125/145)
Measure Participants	0	0

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	46/282 (16.3%)		55/288 (19.1%)
Serious Adverse Events
	EBRT + Brachytherapy		Brachytherapy Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	52/282 (18.4%)		41/288 (14.2%)
Blood and lymphatic system disorders
Hemoglobin decreased	1/282 (0.4%)		0/288 (0%)
Cardiac disorders
Circulatory or cardiac-Other	0/282 (0%)		1/288 (0.3%)
Myocardial ischaemia	1/282 (0.4%)		0/288 (0%)
Supraventricular arrhythmia NOS	1/282 (0.4%)		0/288 (0%)
Gastrointestinal disorders
Diarrhea NOS	1/282 (0.4%)		0/288 (0%)
GI-other	1/282 (0.4%)		0/288 (0%)
Ileus	0/282 (0%)		1/288 (0.3%)
Late RT Toxicity: Other GI : NOS	1/282 (0.4%)		3/288 (1%)
Late RT Toxicity: Small/Large Intestine: NOS	6/282 (2.1%)		3/288 (1%)
Melaena	1/282 (0.4%)		0/288 (0%)
Proctitis NOS	0/282 (0%)		1/288 (0.3%)
General disorders
Late RT Toxicity: Other : NOS	14/282 (5%)		9/288 (3.1%)
Infections and infestations
Infection NOS	1/282 (0.4%)		0/288 (0%)
Metabolism and nutrition disorders
Hyponatremia	0/282 (0%)		1/288 (0.3%)
Nervous system disorders
Cerebral ischaemia	1/282 (0.4%)		0/288 (0%)
Headache NOS	1/282 (0.4%)		0/288 (0%)
Renal and urinary disorders
Dysuria	1/282 (0.4%)		2/288 (0.7%)
Late RT Toxicity: Bladder/Other GU : NOS	22/282 (7.8%)		9/288 (3.1%)
Renal/GU-Other	0/282 (0%)		1/288 (0.3%)
Ureteric obstruction	0/282 (0%)		1/288 (0.3%)
Urinary frequency	10/282 (3.5%)		7/288 (2.4%)
Urinary retention	4/282 (1.4%)		4/288 (1.4%)
Reproductive system and breast disorders
Impotence	1/282 (0.4%)		6/288 (2.1%)
Other (Not Including Serious) Adverse Events
	EBRT + Brachytherapy		Brachytherapy Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	220/282 (78%)		208/288 (72.2%)
Gastrointestinal disorders
Diarrhea NOS	26/282 (9.2%)		6/288 (2.1%)
Late RT Toxicity: Other GI : NOS	78/282 (27.7%)		34/288 (11.8%)
Late RT Toxicity: Small/Large Intestine: NOS	88/282 (31.2%)		37/288 (12.8%)
General disorders
Fatigue	25/282 (8.9%)		4/288 (1.4%)
Late RT Toxicity: Other : NOS	121/282 (42.9%)		99/288 (34.4%)
Renal and urinary disorders
Dysuria	52/282 (18.4%)		28/288 (9.7%)
Late RT Toxicity: Bladder/Other GU : NOS	160/282 (56.7%)		147/288 (51%)
Urinary frequency	96/282 (34%)		88/288 (30.6%)
Urinary retention	26/282 (9.2%)		36/288 (12.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.