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

Prostate Cancer Clinical Trial

Official title:

A PHASE III TRIAL OF THE STUDY OF ENDOCRINE THERAPY USED AS A CYTOREDUCTIVE AND CYTOSTATIC AGENT PRIOR TO RADIATION THERAPY IN GOOD PROGNOSIS LOCALLY CONFINED ADENOCARCINOMA OF THE PROSTATE

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002597
• Other study ID #: RTOG-9408
• Secondary ID: CDR0000063821
• Status: Completed
• Phase: Phase 3
• Start date: October 1994
• Est. completion date: May 14, 2018

Study information

• Verified date: May 2018
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy (RT) uses high-energy x-rays to damage tumor cells. Androgens can stimulate the growth of prostate cancer cells. Hormone therapy using flutamide, goserelin, and leuprolide may fight prostate cancer by reducing the production of androgens. It is not yet known which regimen of antiandrogen therapy is most effective for prostate cancer.

PURPOSE: Randomized phase III trial to study the effectiveness of radiation therapy with or without antiandrogen therapy in treating patients who have stage I or stage II prostate cancer.

Description:

OBJECTIVES: Primary: To evaluate whether a combination of Zoladex and flutamide used as cytoreductive agents prior to and during definitive radiation therapy improves overall survival over radiation therapy alone in locally confined carcinomas of the prostate; Secondary: To compare the rates of disease-specific survival, clinical relapse (local progression and/or distant failure), freedom from prostate-specific antigen (PSA) failure, freedom from second clinical relapse, freedom from second PSA relapse, and disease-free survival; To compare the prostate re-biopsy at two years; To measure the effect on sexual function.

OUTLINE: This is a randomized, multicenter study. Patients were stratified by PSA level (less than 4 vs 4-20), tumor differentiation (well vs moderate vs poor), nodal status (N0 [nodes evaluated by surgical sampling] vs NX [nodes evaluated negative by imaging methods only]), and participating center. Patients are randomized to one of two treatment arms. Arm I: Patients receive oral flutamide 3 times a day and goserelin subcutaneously once every 4 weeks, or once as a time release injection (intramuscular leuprolide may be substituted for goserelin), beginning 2 months prior to radiotherapy and continuing until completion of radiotherapy. Patients undergo radiotherapy daily 4-5 days per week for almost 8 weeks. Arm II: Patients undergo radiotherapy only, as in arm I. Patients are followed every 3 months for the remainder of the first year, every 4 months for the second year, every 6 months for the third through fifth years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1980 patients within 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2028
• Est. completion date: May 14, 2018
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Histologically confirmed locally confined adenocarcinoma of the prostate with primary tumors confined to the prostate, clinical stage T1b,1c, 2a or 2b.

• Negative nodes evaluated by imaging methods (classified in the study as NX) or by surgical sampling (classified in the study as N0).

• Karnofsky performance status = 70.

• PSA is mandatory, must be = 20)

• No prior hormonal therapy, radiation or chemotherapy.

• Prior finasteride for prostate hypertrophy allowed if discontinued at least 60 days prior to randomization.

• Prior testosterone administration allowed if at least 90 days elapsed since last administration.

• No evidence of distant metastasis or other synchronous primary. Patients with prior invasive malignancy who were disease free for at least 5 years could be eligible with pre-randomization approval by the study chairman.

• Treatment begins within 21 days after randomization.

• Patients signs a study-specific informed consent form.

• Alanine Aminotransferase (ALT) within 2x upper normal limits.

Exclusion criteria:

• Stage T1a or = T2c disease.

• Lymph node involvement (N1 - N3).

• Evidence of distant metastasis. (M1)

• PSA > 20.

• Radical surgery or cryosurgery for carcinoma of the prostate, previous irradiation, antiandrogen therapy or chemotherapy.

• Previous or concurrent cancers other than basal cell or squamous cell skin carcinoma.

Patients with squamous cell carcinomas required to be NED (no evidence of disease) for a minimum of two years prior to study entry.

• Major medical or psychiatric illness which, in the investigator's opinion, would prevent completion of treatment and would interfere with follow-up.

• Karnofsky performance status of < 70.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• flutamide
Two 125 mg capsules (t.i.d., p.o.) beginning two months before RT and continuing until RT is completed.
• Zoladex
3.6 mg s.c. monthly x 4 beginning two months before RT and continuing until RT is completed. The 3-month preparation may be used instead of three separate monthly injections.
• Lupron
7.5 mg IM (intramuscular) monthly x 4 beginning two months before RT and continuing until RT is completed. The 3-month preparation may be used instead of three separate monthly injections.

Radiation:
• radiation therapy
46.8 Gy (1.8 Gy/day four to five times a week [26 fx]) to regional lymphatics followed by 19.8 Gy (1.8 Gy/day x 11 fx) for a total of 66.6 Gy to the prostate. Prostate only may be treated in defined circumstances.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Center - Calgary	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	CHUS-Hopital Fleurimont	Fleurimont	Quebec
Canada	Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Cancer Care Ontario-Hamilton Regional Cancer Centre	Hamilton	Ontario
Canada	Kingston Regional Cancer Centre	Kingston	Ontario
Canada	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario
Canada	McGill University	Montreal	Quebec
Canada	Ottawa Regional Cancer Centre - General Campus	Ottawa	Ontario
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Newfoundland Cancer Treatment and Research Foundation	St. Johns	Newfoundland and Labrador
Canada	Northeastern Ontario Regional Cancer Centre, Sudbury	Sudbury	Ontario
Canada	Northwestern Ontario Regional Cancer Centre, Thunder Bay	Thunder Bay	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
United States	Akron City Hospital	Akron	Ohio
United States	Akron General Medical Center	Akron	Ohio
United States	Cancer Center of Albany Medical Center	Albany	New York
United States	Saint Joseph Medical Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	Harrington Cancer Center	Amarillo	Texas
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	St. John's Medical Center	Anderson	Indiana
United States	CCOP - Ann Arbor Regional	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Anne Arundel Oncology Center	Annapolis	Maryland
United States	Northwest Community Hospital	Arlington Heights	Illinois
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Greater Baltimore Medical Center and Cancer Center	Baltimore	Maryland
United States	Harbor Hospital Center	Baltimore	Maryland
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
United States	Radiation Oncology Affiliates of Maryland, P.A.	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Julie and Ben Rogers Cancer Institute	Beaumont	Texas
United States	CCOP - Southwestern Vermont Regional Cancer Center	Bennington	Vermont
United States	St. Luke's Hospital Regional Cancer Center	Bethlehem	Pennsylvania
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Albert Einstein Comprehensive Cancer Center	Bronx	New York
United States	New York Methodist Hospital	Brooklyn	New York
United States	State University of New York Health Science Center at Brooklyn	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Vermont Cancer Center	Burlington	Vermont
United States	Cooper Cancer Institute	Camden	New Jersey
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Cancer Center at the University of Virginia	Charlottesville	Virginia
United States	Martha Jefferson Hospital	Charlottesville	Virginia
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Christ Hospital	Cincinnati	Ohio
United States	Lykes Center for Radiation Therapy	Clearwater	Florida
United States	Ireland Cancer Center	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Finger Lakes Radiation Oncology, P.C.	Clifton Springs	New York
United States	Memorial Hospital Cancer Center	Colorado Springs	Colorado
United States	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Medical Center/John B. Amos Community Cancer Center	Columbus	Georgia
United States	Mount Diablo Medical Center	Concord	California
United States	Northeast Medical Center	Concord	North Carolina
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Mercy Catholic Medical Center, Mercy Fitzgerald Divison	Darby	Pennsylvania
United States	Halifax Medical Center	Daytona Beach	Florida
United States	CCOP - Central Illinois	Decatur	Illinois
United States	University of Colorado Cancer Center	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	Cancer Center and Beckman Research Institute, City of Hope	Duarte	California
United States	Wendt Regional Cancer Center of Finley Hospital	Dubuque	Iowa
United States	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey
United States	John F. Kennedy Medical Center	Edison	New Jersey
United States	Provena St. Joseph Hospital- Regional Cancer Care Center	Elgin	Illinois
United States	Trinitas Hospital - Jersey Street Campus	Elizabeth	New Jersey
United States	Meritcare Roger Maris Cancer Center	Fargo	North Dakota
United States	Hurley Medical Center	Flint	Michigan
United States	McLaren Regional Cancer Center	Flint	Michigan
United States	Radiation Therapy Associates - Fort Myers	Fort Myers	Florida
United States	California Cancer Center	Fresno	California
United States	Saint Agnes Cancer Center	Fresno	California
United States	University of Florida Health Science Center	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	Glendale Memorial Hospital and Health Center	Glendale	California
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Sutter Health Western Division Cancer Research Group	Greenbrae	California
United States	CCOP - Greenville	Greenville	South Carolina
United States	East Carolina University School of Medicine	Greenville	North Carolina
United States	RMH Regional Canter Center	Harrisonburg	Virginia
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Penn State Geisinger Cancer Center	Hershey	Pennsylvania
United States	Catawba Memorial Hospital	Hickory	North Carolina
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Comprehensive Cancer Institute of Huntsville	Huntsville	Alabama
United States	Huntsville Hospital System	Huntsville	Alabama
United States	Cape Cod Hospital	Hyannis	Massachusetts
United States	Clarion Health Partners Inc.	Indianapolis	Indiana
United States	Community Hospitals of Indianapolis - Regional Cancer Center	Indianapolis	Indiana
United States	Veterans Affairs Medical Center - Indianapolis (Roudebush)	Indianapolis	Indiana
United States	Holden Comprehensive Cancer Center at The University of Iowa	Iowa City	Iowa
United States	Jackson-Madison County General Hospital	Jackson	Tennessee
United States	Veterans Affairs Medical Center - Boston (Jamaica Plain)	Jamaica Plain	Massachusetts
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	CCOP - Dayton	Kettering	Ohio
United States	Gundersen Lutheran Medical Foundation	La Crosse	Wisconsin
United States	University of California San Diego Cancer Center	La Jolla	California
United States	Wilford Hall - 59th Medical Wing	Lackland Air Force Base	Texas
United States	Romagosa Radiation Oncology Center	Lafayette	Louisiana
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky
United States	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Veterans Affairs Medical Center - Long Beach	Long Beach	California
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	Louisville Radiation Oncology	Louisville	Kentucky
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Southern Wisconsin Radiotherapy Center	Madison	Wisconsin
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Merle M. Mahr Cancer Center	Madisonville	Kentucky
United States	Elliot Regional Cancer Center	Manchester	New Hampshire
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	Marquette General Hospital	Marquette	Michigan
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Loyola University Medical Center	Maywood	Illinois
United States	Health First Holmes Regional Medical Center	Melbourne	Florida
United States	University of Tennessee, Memphis Cancer Center	Memphis	Tennessee
United States	Community Memorial Hospital	Menomonee Falls	Wisconsin
United States	Baptist Hospital of Miami	Miami	Florida
United States	dVeterans Affairs Medical Center - Miami	Miami	Florida
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	MidMichigan Medical Center - Midland	Midland	Michigan
United States	South Jersey Regional Cancer Center	Millville	New Jersey
United States	Columbia Hospital	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	St. Joseph's Hospital	Milwaukee	Wisconsin
United States	St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee (Zablocki)	Milwaukee	Wisconsin
United States	MBCCOP - Gulf Coast	Mobile	Alabama
United States	Alabama Oncology, LLC	Montgomery	Alabama
United States	Fox Chase Cancer Center at Virtua Memorial Hospital Burlington County	Mount Holly	New Jersey
United States	Ball Memorial Hospital	Muncie	Indiana
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Beth Israel Medical Center	New York	New York
United States	Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	St. Anthony Hospital	Oklahoma City	Oklahoma
United States	Methodist Cancer Center - Omaha	Omaha	Nebraska
United States	Nebraska Health System	Omaha	Nebraska
United States	Florida Radiation Oncology Group	Orange Park	Florida
United States	MD Anderson Cancer Center Orlando	Orlando	Florida
United States	Bay Medical Center	Panama City	Florida
United States	Gulf Coast Cancer Treatment Center	Panama City	Florida
United States	Lutheran General Cancer Care Center	Park Ridge	Illinois
United States	Bayshore Medical Center	Pasadena	Texas
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Hahnemann University Hospital	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center of Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	Veterans Affairs Medical Center - Philadelphia	Philadelphia	Pennsylvania
United States	Mercy Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Champlain Valley Physicians Hospital Medical Center	Plattsburgh	New York
United States	Atlantic City Medical Center	Pomona	New Jersey
United States	Cancer Care Center	Pomona	California
United States	CCOP - Columbia River Program	Portland	Oregon
United States	Maine Medical Center	Portland	Maine
United States	Vassar Brothers Hospital	Poughkeepsie	New York
United States	Roger Williams Medical Center/BUSM	Providence	Rhode Island
United States	Southeastern Wisconsin Regional Cancer Center	Racine	Wisconsin
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	University of Rochester Cancer Center	Rochester	New York
United States	InterCommunity Cancer Center at Rome	Rome	Georgia
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Green Mountain Oncology Group	Rutland	Vermont
United States	Radiation Oncology Center - Sacramento	Sacramento	California
United States	St. Mary's Medical Center	Saginaw	Michigan
United States	Dixie Regional Medical Center	Saint George	Utah
United States	Mallinckrodt Institute of Radiology	Saint Louis	Missouri
United States	St. Louis University Health Sciences Center	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Peninsula Regional Medical Center	Salisbury	Maryland
United States	LDS Hospital	Salt Lake City	Utah
United States	University of Utah Health Sciences Center	Salt Lake City	Utah
United States	Radiation Medical Group, Inc.	San Diego	California
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	O'Connor Hospital	San Jose	California
United States	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California
United States	Sarasota Radiation and Medical Oncology Center	Sarasota	Florida
United States	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania
United States	Virginia Mason Medical Center	Seattle	Washington
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Deaconess Medical Center	Spokane	Washington
United States	Cancer Research for the Ozarks	Springfield	Missouri
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Tallahassee Memorial Healthcare	Tallahassee	Florida
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	CCOP - Toledo Community Hospital Oncology Program	Toledo	Ohio
United States	Community Medical Center	Toms River	New Jersey
United States	Capital Health System at Mercer	Trenton	New Jersey
United States	St. Francis Medical Center	Trenton	New Jersey
United States	Arizona Cancer Center	Tucson	Arizona
United States	St. John Health System	Tulsa	Oklahoma
United States	North Mississippi Medical Center/Cancer Center	Tupelo	Mississippi
United States	Radiation Oncology Associates of West Alabama	Tuscaloosa	Alabama
United States	East Texas Medical Center - Cancer Institute	Tyler	Texas
United States	New York Medical College	Valhalla	New York
United States	Associated Radiologists, P.A.	Warren	New Jersey
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	Schiffler Cancer Center	Wheeling	West Virginia
United States	Wilkes Barre General Hospital	Wilkes-Barre	Pennsylvania
United States	CCOP - Christiana Care Health Services	Wilmington	Delaware
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania
United States	Yakima Valley Memorial Hospital	Yakima	Washington
United States	York Hospital	York	Pennsylvania

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (5)

Bruner D, Scott C, McGowan D, et al.: Factors influencing sexual outcomes in prostate cancer patients enrolled on radiation therapy oncology group studies 90-20 and 94-08. [Abstract] Proceedings of the International Society for Quality of Life Research 7: 575, 1998.

Bruner DW, Scott CB, McGowan D, et al.: Validation of the sexual adjustment questionnaire (SAQ) in prostate cancer patients enrolled on Radiation Therapy Oncology Group studies 90-20 and 94-08. [Abstract] Int J Radiat Oncol Biol Phys 42 (suppl 1): A-156, 202, 1998.

Johnke RM, Edwards JM, Evans MJ, Nangami GN, Bakken NT, Kilburn JM, Lee TK, Allison RR, Karlsson UL, Arastu HH. Circulating cytokine levels in prostate cancer patients undergoing radiation therapy: influence of neoadjuvant total androgen suppression. In Vivo. 2009 Sep-Oct;23(5):827-33. — View Citation

Jones CU, Hunt D, McGowan DG, Amin MB, Chetner MP, Bruner DW, Leibenhaut MH, Husain SM, Rotman M, Souhami L, Sandler HM, Shipley WU. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med. 2011 Jul 14;365(2):107-18. d — View Citation

McGowan D, Hunt D, Jones C, et al.: Effect of short-term endocrine therapy prior to and during radiation therapy on overall survival in patients with T1b-T2b adenocarcinoma of the prostate and PSA equal to or less than 20: initial results of RTOG 94-08. [

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival Rate (10-year)	Overall survival (OS) was calculated from randomization to the date of death from any cause and overall survival rates were estimated by the Kaplan-Meier method.	From date of randomization to 10 years
Secondary	Disease-specific Survival Rate (10 Years)	Disease-specific failure is defined as death certified as due to prostate cancer (by central review), death due to complications of treatment (irrespective of malignancy status), death from unknown causes with active malignancy, or death from unknown causes with previously documented relapse (either clinical or biochemical). Survival rates were estimated by means of cumulative incidence functions.	From registration to 10 years
Secondary	Local Progression Rate (10 Years)	Local progression defined as documented local progression as determined by clinical exam . Failure rates were estimated by means of cumulative incidence functions.	From registration to 10 years
Secondary	Distant Failure Rate (10 Years)	Failure is defined as documented metastatic disease. Failure rates were estimated by means of cumulative incidence functions.	From registration to 10 years
Secondary	Biochemical Failure Rate (10 Years)	The Phoenix definition of biochemical failure was used - an increase in the prostate-specific antigen (PSA) level of >2 ng per milliliter above the nadir. Failure rates were estimated by means of cumulative incidence functions.	From registration to 10 years
Secondary	Clinical Relapse Rate (10 Years)	Clinical relapse is defined as local progression or distant metastases. Failure rates were estimated by means of cumulative incidence functions.	From registration to 10 years
Secondary	Second Biochemical Relapse Rate (10 Years)	Second biochemical relapse is as defined as follows (after initiation of salvage hormone therapy): A rise in PSA on at least two consecutive cases above the nadir (after initiation of salvage hormone therapy), with the rises in PSA exceeding 1 ng/ml above the nadir; or failure to reach 4 ng/L or less at 18 months. The rates of second biochemical relapse were estimated by means of cumulative incidence functions.	From registration to 10 years
Secondary	Disease-free Survival Rate (10 Years)	Disease-free failure is defined as documentation of progression (local progression, distant failure, and biochemical failure) or death from any cause. Disease-free survival rates were estimated by the Kaplan-Meier method.	From registration to 10 years
Secondary	Positive Re-biopsy Rate at Two Years	The rate of prostate rebiopsy at two years is defined as the proportion of patients whose results are positive among all eligible patients who had a repeat biopsy at two years. The rate was estimated separately in each arm.	From registration to two years