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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00063882
• Other study ID #: RTOG 0232
• Secondary ID: CDR0000288823NCI
• Status: Completed
• Phase: Phase 3
• Start date: June 2003
• Est. completion date: December 22, 2022

Study information

• Verified date: December 2022
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 588
• Est. completion date: December 22, 2022
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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.
• Brachytherapy (125/145)
125 Gy Palladium-103 (P-103) or 145 Gy Iodine-125 (I-125) seeds within 4 weeks of study entry.
• 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.

Locations

Country	Name	City	State
Canada	Cross Cancer Institute at University of Alberta	Edmonton	Alberta
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	Radiation Oncology Center	Alliance	Ohio
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Auburn Radiation Oncology	Auburn	California
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	St. Agnes Hospital Cancer Center	Baltimore	Maryland
United States	Barberton Citizens Hospital	Barberton	Ohio
United States	Alta Bates Summit Comprehensive Cancer Center	Berkeley	California
United States	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	New York Methodist Hospital	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Peninsula Medical Center	Burlingame	California
United States	Radiation Oncology Centers - Cameron Park	Cameron Park	California
United States	Sands Cancer Center	Canandaigua	New York
United States	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Valley Medical Oncology Consultants - Castro Valley	Castro Valley	California
United States	Sandra L. Maxwell Cancer Center	Cedar City	Utah
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Community Cancer Center	Elyria	Ohio
United States	Hematology Oncology Center	Elyria	Ohio
United States	St. Francis Hospital	Federal Way	Washington
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Valley Medical Oncology	Fremont	California
United States	California Cancer Center - Woodward Park Office	Fresno	California
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Kaiser Permanente Medical Center - Hayward	Hayward	California
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Cape Cod Hospital	Hyannis	Massachusetts
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Parvin Radiation Oncology	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri
United States	St. Joseph Medical Center	Kansas City	Missouri
United States	Kingsbury Center for Cancer Care at Cheshire Medical Center	Keene	New Hampshire
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Nevada Cancer Institute	Las Vegas	Nevada
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Liberty Hospital	Liberty	Missouri
United States	Lima Memorial Hospital	Lima	Ohio
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Logan Regional Hospital	Logan	Utah
United States	Shields Radiation Oncology Center - Mansfield	Mansfield	Massachusetts
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	Columbia Saint Mary's Hospital - Ozaukee	Mequon	Wisconsin
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Columbia-Saint Mary's Cancer Care Center	Milwaukee	Wisconsin
United States	Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Coleman Radiation Oncology Center at Carter General Hospital	Morehead City	North Carolina
United States	El Camino Hospital Cancer Center	Mountain View	California
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	CarolinaEast Cancer Care	New Bern	North Carolina
United States	Hospital of Saint Raphael	New Haven	Connecticut
United States	Beth Israel Medical Center - Petrie Division	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Sutter Health - Western Division Cancer Research Group	Novato	California
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Breast Surgeons, Incorporated	Oakland	California
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Kaiser Permanente - Division of Research - Oakland	Oakland	California
United States	Kaiser Permanente Medical Center - Oakland	Oakland	California
United States	Larry G Strieff MD Medical Corporation	Oakland	California
United States	Tom K Lee, Incorporated	Oakland	California
United States	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Menorah Medical Center	Overland Park	Kansas
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	Arizona Oncology Services Foundation	Phoenix	Arizona
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	CCOP - Kansas City	Prairie Village	Kansas
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	Good Samaritan Cancer Center	Puyallup	Washington
United States	South Suburban Oncology Center	Quincy	Massachusetts
United States	All Saints Cancer Center at Wheaton Franciscan Healthcare	Racine	Wisconsin
United States	Kaiser Permanente Medical Center - Rancho Cordova	Rancho Cordova	California
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Kaiser Permanente Medical Center - Redwood City	Redwood City	California
United States	Renown Institute for Cancer at Renown Regional Medical Center	Reno	Nevada
United States	Kaiser Permanente Medical Center - Richmond	Richmond	California
United States	Veterans Affairs Medical Center - Richmond	Richmond	Virginia
United States	Highland Hospital of Rochester	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	University Radiation Oncology at Parkridge Hospital	Rochester	New York
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	Kaiser Permanente Medical Center - Roseville	Roseville	California
United States	Radiation Oncology Center - Roseville	Roseville	California
United States	Kaiser Permanente Medical Center - Sacramento	Sacramento	California
United States	Mercy General Hospital	Sacramento	California
United States	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California
United States	South Sacramento Cancer Center	Sacramento	California
United States	South Sacramento Kaiser-Permanente Medical Center	Sacramento	California
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	Norris Cotton Cancer Center - North	Saint Johnsbury	Vermont
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Saint Joseph Oncology, Incorporated	Saint Joseph	Missouri
United States	Barnes-Jewish West County Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - St. Peters	Saint Peters	Missouri
United States	Cancer Care Center, Incorporated	Salem	Ohio
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	California Pacific Medical Center - California Campus	San Francisco	California
United States	Kaiser Permanente Medical Center - San Francisco Geary Campus	San Francisco	California
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Kaiser Permanente Medical Center - Santa Teresa	San Jose	California
United States	Kaiser Foundation Hospital - San Rafael	San Rafael	California
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara Kiely Campus	Santa Clara	California
United States	Kaiser Permanente Medical Center - Santa Rosa	Santa Rosa	California
United States	Kaiser Permanente Medical Center - South San Francisco	South San Francisco	California
United States	Cancer Institute at St. John's Hospital	Springfield	Illinois
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	Kaiser Permanente Medical Facility - Stockton	Stockton	California
United States	South Atlantic Radiation Oncology, LLC	Supply	North Carolina
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	CCOP - Northwest	Tacoma	Washington
United States	Franciscan Cancer Center at St. Joseph Medical Center	Tacoma	Washington
United States	MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	Washington
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Anne Mercy Hospital	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	Solano Radiation Oncology Center	Vacaville	California
United States	Sutter Solano Medical Center	Vallejo	California
United States	Fox Chase Virtua Health Cancer Program at Virtua West Jersey	Voorhees	New Jersey
United States	Kaiser Permanente Medical Center - Walnut Creek	Walnut Creek	California
United States	St. John Macomb Hospital	Warren	Michigan
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	West Allis Memorial Hospital	West Allis	Wisconsin
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Coastal Carolina Radiation Oncology Center	Wilmington	North Carolina
United States	Winchester Hospital Radiation Oncology Center	Winchester	Massachusetts
United States	Cancer Treatment Center	Wooster	Ohio
United States	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.
Primary	5-Year Freedom From Progression Rate	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.	From randomization to 5 years
Secondary	Biochemical Failure Rate (Protocol Definition)	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.	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.
Secondary	Biochemical Failure (Phoenix Definition)	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.	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.
Secondary	Prostate Cancer Death	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.	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.
Secondary	Local Failure	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.	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.
Secondary	Distant Metastases	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.	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.
Secondary	Overall Survival	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.	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.
Secondary	Percentage of Patients With Acute Grade 2+ and Grade 3+ Toxicities [Genitourinary (GU), Gastrointestinal (GI), and Overall]	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.	Zero to 180 days from the start of radiation
Secondary	Time to Late Grade 3+ Toxicities [Genitourinary (GU), Gastrointestinal (GI), and Overall]	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.	From 181 days after the start of radiation to last follow-up. Maximum follow-up at time of analysis was 13.9 years.
Secondary	Change in Expanded Prostate Cancer Index Composite (EPIC) From Baseline to 4 Months	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.	Baseline and 4 months after start of radiation
Secondary	Change in Expanded Prostate Cancer Index Composite (EPIC) From Baseline to 24 Months	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.	Baseline and 24 months after start of radiation
Secondary	Change in Total American Urological Association Symptom Index (AUA-SI) Score From Baseline to 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.	Baseline and 4 months after start of radiation
Secondary	Change in Total American Urological Association Symptom Index (AUA-SI) Score From Baseline to 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.	Baseline and 24 months after start of radiation
Secondary	Change in European Quality of Life-5 Domains (EQ-5D) From Baseline to 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.	Baseline and 4 months after start of radiation
Secondary	Change in European Quality of Life-5 Domains (EQ-5D) From Baseline to 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.	Baseline and 24 months after start of radiation