Hormone Therapy and Radiation Therapy in Treating Patients With Prostate Cancer

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00005044
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 1,579
• Locations: 261
• Arms: 2
• Actual Duration (Months): 267.6
• Patients Per Site: 6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Hormones can stimulate the growth of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which regimen of hormone therapy and radiation therapy is more effective for prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of two different regimens of hormone therapy and radiation therapy in treating patients who have prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Casodex; Drug: Eulexin; Drug: LHRH agonist; Radiation: radiation therapy	Phase 3

Detailed Description

OBJECTIVES:

• Compare the efficacy of moderate-duration (28 weeks) neoadjuvant total androgen suppression (TAS) and radiotherapy (RT) with short-duration (8 weeks) neoadjuvant TAS and RT, as related to disease-specific survival, in patients with intermediate-risk adenocarcinoma of the prostate.

• Compare these regimens, in terms of overall survival, disease-free survival, time to local tumor progression or distant failure, time to first biochemical failure, hormone-refractory state, and treatment-induced morbidity, in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prostate-specific antigen level (no greater than 10 ng/mL vs greater than 10 but no greater than 20 ng/mL vs greater than 20 ng/mL), tumor stage (T1b-2 vs T3-4), Gleason score (2-4 vs 5-6 vs 7-10), and prior hormonal therapy (yes vs no). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive total androgen suppression for 8 weeks prior to the initiation of radiotherapy and throughout radiotherapy. A luteinizing hormone-releasing hormone (LHRH) agonist is administered every 1-3 months AND bicalutamide OR flutamide is given orally daily for a total duration of 16 weeks. Beginning with week 9, patients undergo radiotherapy 5 days a week for 8 weeks.

• Arm II: Patients receive total androgen suppression for 28 weeks prior to the initiation of radiotherapy and throughout radiotherapy. An LHRH agonist AND bicalutamide OR flutamide are administered as in arm I for a total duration of 36 weeks. Beginning with week 29, patients undergo radiotherapy as in arm I.

Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,540 patients (770 per treatment arm) will be accrued for this study within 4 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1579 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Trial to Evaluate the Duration of Neoadjuvant Total Androgen Suppression (TAS) and Radiation Therapy (RT) in Intermediate-Risk Prostate Cancer
• Actual Study Start Date: Feb 1, 2000
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: May 20, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAS x 8 weeks Total Androgen Suppression (TAS) (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by radiation therapy (RT) with concurrent TAS (LHRH agonist and Casodex or Eulexin).	Drug: Casodex; Orally at a dose of one 50 mg tablet per day started within (before or after) 14 days of the first LHRH agonist injection.; Other Names: bicalutamide ; Drug: Eulexin; Orally at a dose of two 125 mg capsules three times a day for a total daily dose of 750 mg (six capsules) started within (before or after) 14 days of the first LHRH agonist injection.; Other Names: flutamide ; Drug: LHRH agonist; LHRH agonist of choice. The manufacturer's instructions should be followed.; Other Names: Zoladex Lupron Eligard Viadur luteinizing hormone-releasing hormone (LHRH)-agonist ; Radiation: radiation therapy; [Prostate and any extraprostatic tumor extension + 1.0-1.5 cm margin receives 70.2 Gy (1.8 Gy/day x 39 fractions, five days/week)] OR [regional nodes, prostate and seminal vesicles + 1.0-1.5 cm margin will receive 46.8 Gy (1.8 Gy/day x 26 fractions, five days/week), followed by a 23.4 Gy (1.8 Gy/day x 13 fractions, five days/week) boost to the prostate and any extraprostatic tumor extension + 1.0-1.5 cm margin]
Experimental: TAS x 28 weeks TAS (LHRH agonist and Casodex or Eulexin) x 28 weeks followed by RT with concurrent TAS (LHRH agonist and Casodex or Eulexin).	Drug: Casodex; Orally at a dose of one 50 mg tablet per day started within (before or after) 14 days of the first LHRH agonist injection.; Other Names: bicalutamide ; Drug: Eulexin; Orally at a dose of two 125 mg capsules three times a day for a total daily dose of 750 mg (six capsules) started within (before or after) 14 days of the first LHRH agonist injection.; Other Names: flutamide ; Drug: LHRH agonist; LHRH agonist of choice. The manufacturer's instructions should be followed.; Other Names: Zoladex Lupron Eligard Viadur luteinizing hormone-releasing hormone (LHRH)-agonist ; Radiation: radiation therapy; [Prostate and any extraprostatic tumor extension + 1.0-1.5 cm margin receives 70.2 Gy (1.8 Gy/day x 39 fractions, five days/week)] OR [regional nodes, prostate and seminal vesicles + 1.0-1.5 cm margin will receive 46.8 Gy (1.8 Gy/day x 26 fractions, five days/week), followed by a 23.4 Gy (1.8 Gy/day x 13 fractions, five days/week) boost to the prostate and any extraprostatic tumor extension + 1.0-1.5 cm margin]

Outcome Measures

Primary Outcome Measures

1. Disease-specific Survival (DSS) (10-year Rates Reported) [From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)]

   Disease-specific survival time is measured from date of randomization to death due to prostate cancer based on study chair review, with prostate-cancer death defined as (1) primary cause of death certified as due to prostate cancer, (2) complication of therapy, irrespective of disease status, (3) disease progression in the absence of any anti-tumor therapy, or (4) a 1.0 ng/ml-exceeding-rise in serum prostate-specific antigen (PSA) level on at least two consecutive occasions that occurs during or after salvage androgen suppression therapy. Death due to other causes is considered a competing risk. All others are censored. DSS is estimated using the cumulative incidence method. Ten-year rate is reported.

Secondary Outcome Measures

1. Overall Survival (OS) (10-year Rates Reported) [From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)]

   Survival time is defined as time from randomization to the date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Ten-year rate is reported.

2. Disease-free Survival (DFS) (10-year Rates Reported) [From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)]

   Disease-free survival time is defined as time from randomization to the date of disease progression or death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Ten-year rate is reported.

3. Clinical Patterns of Tumor Recurrence: Time to Locoregional Progression (LRP) and Time to Distant Metastasis (DM) (10 Year Rates Reported) [From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)]

   Time to distant metastasis measured from date of randomization to date of documented distant metastasis; competing risks are BF, LRP, and death without DM; all others are censored. Time to locoregional progression measured from date of randomization to date of documented local or regional progression; competing risks are BF [protocol definition- first of (1) the midway date between the last non-rising PSA and the first rising PSA of three consecutive rises or (2) the date of the initiation of salvage hormone therapy], DM, and death without LRP; all others are censored. LRP and DM are estimated using the cumulative incidence method. Ten -year rates are reported.

4. Time to First Biochemical Failure (BF) (10-year Rates Reported) [From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)]

   Protocol definition: Time to BF measured from date of randomization to first of (1) the midway date between the last non-rising PSA and the first rising PSA of three consecutive rises or (2) the date of the initiation of salvage hormone therapy; competing risks are LRP, DM, and death without BF; all others are censored. Phoenix definition: Time to BF measured from date of randomization to first of (1) the date of documented rise of 2 ng/ml above the post-treatment(RT end date) nadir or (2) the date of the initiation of salvage hormone therapy; competing risks are LRP, DM, and death without BF; all others are censored. For both definitions BF is estimated using the cumulative incidence method. Ten year rates reported.

5. Time to Second Biochemical Failure (SBF) (10-year Rates Reported) [From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)]

   Time to SBF measured from date of randomization to the date of PSA increase of ≥1.0 ng/mL (from the nadir PSA after completion of protocol-specified therapy) after salvage androgen suppression was started; competing risks LRP, DM, and death without SBF; all others are censored. SBF is estimated using the cumulative incidence method. Ten-year rates are reported.

6. Treatment-induced Morbidity (Highest Grade Toxicity Reported Per Patient) [From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)]

   Acute drug therapy and radiation (<= 90 days from start of RT) toxicity was graded using the Common Toxicity Criteria (CTC) v.2.0 criteria; late toxicity was graded using the Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) Late Radiation Morbidity Scoring schema. Grade refers to the severity of the toxicity. The CTC v2.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1 Mild toxicity, Grade 2 Moderate toxicity, Grade 3 Severe toxicity, Grade 4 Life-threatening or disabling toxicity, Grade 5 Death related to toxicity. The highest grade acute and late toxicity was determined for each patient.

Eligibility Criteria

Criteria

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

Inclusion Criteria

1. Adenocarcinoma of prostatic origin histologically-confirmed within 180 days of the randomization date.

2. Zubrod Performance Status 0-1 (Appendix II).

3. Prostatic biopsy tumor grading by the Gleason Score classification (Appendix VI) is mandatory prior to randomization.

4. Patients at intermediate risk for disease relapse as determined by any of the following combinations of factors (NOTE: tumor found in one or both lobes on biopsy, but not palpable, will not alter T stage):

• Clinical stage T1b-4, Gleason score 2-6, and prostate-specific antigen >10 but ≤

• Clinical stage T1b-4, Gleason score 7, and prostate-specific antigen < 20.

• Clinical stage T1b-1c, Gleason score 8-10, and prostate-specific antigen <20.

1. Clinically negative (N0) lymph nodes (LN) as established by imaging (pelvic ± abdominal CT, MRI or LAG), or negative LN by nodal sampling or dissection (laparoscopy or laparotomy). Patients with radiologic (e.g., CT, MRI or LAG) or radioimmunoscintigraphy (i.e., ProstaScint™) findings suggestive of regional nodal involvement are eligible if cytologic (e.g., needle aspiration) or histologic (e.g., surgical sampling) evaluation shows no evidence of a neoplastic process (i.e., prostatic or non-prostatic malignancy). Patients with equivocal radiologic findings (maximum nodal size ≤ 1.5 cm) are eligible.

2. No distant (M0) metastases. Patients with radionuclide imaging (e.g., bone scintigraphy, ProstaScint™) findings suggestive, but not diagnostic of metastatic disease are eligible if radiologic (e.g., standard or tomographic radiography, or CT/MRI) imaging does not confirm metastatic disease.

3. Pretherapy serum (total) prostate-specific antigen value performed with a Federal Drug Administration approved assay method, e.g. Abbott, Hybritech, etc.

4. Treatment must begin within 6 weeks after randomization.

5. Alanine aminotransferase (ALT) must be within 2 x upper normal limit.

6. Patients must sign a study-specific informed consent form (Appendix I) prior to randomization.

Exclusion Criteria

1. Patients at high risk for disease relapse as determined by either:

• Prostate-specific antigen ≥ 20 and Gleason score ≥ 7 (any T stage).

• Clinical stage ≥T2 and Gleason score ≥ 8 (any prostate-specific antigen).

1. Patients at low risk for disease relapse as determined by:

• Clinical stage ≤T2, Gleason score ≤ 6, and prostate-specific antigen ≤ 10.

1. Clinical stage Tx, T0, or T1a.

2. Histologic or radiologic evidence of tumor involvement of regional lymph nodes (N1) or the presence of metastatic disease (M1).

3. Pretherapy serum prostate-specific antigen level > 100.

4. Co-morbid medical illness which in the opinion of the investigator is expected to result in a life expectancy of <10 years.

5. Any of the following prior therapies:

• Pelvic external beam radiation therapy.

• Radionuclide prostate brachytherapy.

• Prostatectomy or prostatic cryosurgery.

• Prior bilateral orchiectomy.

• Prior androgen suppression therapy; however, patients begun on LHRH agonist therapy remain eligible if (1) LHRH agonists were started no more than 30 days before randomization, and (2) Casodex or Eulexin was (or will be) started no more than 14 days before or after the date that the LHRH agonist injection was given. Any finasteride therapy administered for prostatic hypertrophy must be discontinued.

• Chemotherapy for prostatic carcinoma.

1. Previous or concomitant invasive cancer, other than localized basal cell or squamous cell skin carcinoma (AJCC Stage 0-II), unless continually disease free for at least 5 years.

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

3. The patient's participation in another medical research study that involves prostate cancer treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama	United States	35294-3300
2	Comprehensive Cancer Institute	Huntsville	Alabama	United States	35801
3	Huntsville Hospital	Huntsville	Alabama	United States	35807
4	MBCCOP - Gulf Coast	Mobile	Alabama	United States	36607
5	Montgomery Cancer Center	Montgomery	Alabama	United States	36106-3657
6	DCH Cancer Treatment Center	Tuscaloosa	Alabama	United States	35401
7	Foundation for Cancer Research and Education	Phoenix	Arizona	United States	85013
8	Providence Saint Joseph Medical Center - Burbank	Burbank	California	United States	91505
9	Mount Diablo Medical Center	Concord	California	United States	94524-4110
10	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
11	California Cancer Center	Fresno	California	United States	93720
12	Saint Agnes Cancer Center	Fresno	California	United States	93720
13	Sutter Health Western Division Cancer Research Group	Greenbrae	California	United States	94904
14	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California	United States	92354
15	Veterans Affairs Medical Center - Long Beach	Long Beach	California	United States	90822
16	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90033-0804
17	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1714
18	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609-3305
19	Huntington Cancer Center at Huntington Hospital	Pasadena	California	United States	91105
20	Robert and Beverly Lewis Family Cancer Care Center	Pomona	California	United States	91767
21	Radiation Oncology Center - Sacramento	Sacramento	California	United States	95816
22	Radiation Medical Group, Incorporated	San Diego	California	United States	92101
23	Naval Medical Center - San Diego	San Diego	California	United States	92134-3202
24	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
25	O'Connor Hospital	San Jose	California	United States	95128
26	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California	United States	95403
27	Torrance Memorial Medical Center	Torrance	California	United States	90505
28	David Grant Medical Center	Travis Air Force Base	California	United States	94535
29	Memorial Hospital Cancer Center	Colorado Springs	Colorado	United States	80909
30	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Denver	Colorado	United States	80010
31	CCOP - Colorado Cancer Research Program, Incorporated	Denver	Colorado	United States	80224
32	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado	United States	81502-1628
33	Hospital of St. Raphael	New Haven	Connecticut	United States	06511
34	Yale Comprehensive Cancer Center	New Haven	Connecticut	United States	06520-8040
35	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
36	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
37	21st Century Oncology - Fort Myers	Fort Myers	Florida	United States	33901-8082
38	Shands Cancer Center at the University of Florida Health Science Center	Gainesville	Florida	United States	32610-0385
39	Florida Radiation Oncology Group	Jacksonville	Florida	United States	32207
40	Holmes Regional Medical Center	Melbourne	Florida	United States	32901-3276
41	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
42	University of Miami Sylvester Cancer Center	Miami	Florida	United States	33136
43	Baptist Hospital of Miami	Miami	Florida	United States	33256-2110
44	MD Anderson Cancer Center Orlando	Orlando	Florida	United States	32806-2134
45	Bay Medical Center	Panama City	Florida	United States	32401
46	Gulf Coast Cancer Treatment Center	Panama City	Florida	United States	32405-4587
47	Sarasota Radiation and Medical Oncology Center	Sarasota	Florida	United States	34233
48	Tallahassee Memorial Hospital	Tallahassee	Florida	United States	32308
49	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612-9497
50	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
51	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342-1701
52	Medical Center/John B. Amos Community Cancer Center	Columbus	Georgia	United States	31901
53	Regional Radiation Oncology Center at Rome	Rome	Georgia	United States	30165
54	MBCCOP - Hawaii	Honolulu	Hawaii	United States	96813
55	Northwest Community Hospital	Arlington Heights	Illinois	United States	60005
56	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
57	CCOP - Central Illinois	Decatur	Illinois	United States	62526
58	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
59	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
60	Lutheran General Cancer Care Center	Park Ridge	Illinois	United States	60068
61	CCOP - Scott and White Hospital	Peoria	Illinois	United States	61602
62	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
63	St. John's Medical Center	Anderson	Indiana	United States	46016
64	Bloomington Hospital	Bloomington	Indiana	United States	47402
65	Veterans Affairs Medical Center - Indianapolis (Roudebush)	Indianapolis	Indiana	United States	46202
66	Methodist Cancer Center at Methodist Hospital	Indianapolis	Indiana	United States	46206-1367
67	Community Regional Cancer Care	Indianapolis	Indiana	United States	46219
68	Ball Memorial Hospital Cancer Center	Muncie	Indiana	United States	47303-3499
69	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
70	Wendt Regional Cancer Center of Finley Hospital	Dubuque	Iowa	United States	52001
71	St. Elizabeth Medical Center	Edgewood	Kentucky	United States	41017
72	Central Baptist Hospital	Lexington	Kentucky	United States	40503
73	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536-0293
74	James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky	United States	40202
75	Louisville Radiation Oncology Center at Caritas Regional Cancer Center	Louisville	Kentucky	United States	40215
76	Merle M. Mahr Cancer Center	Madisonville	Kentucky	United States	42431
77	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
78	Tulane University School of Medicine	New Orleans	Louisiana	United States	70112-2699
79	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
80	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
81	Maine Medical Center	Portland	Maine	United States	04102
82	Anne Arundel Oncology Center	Annapolis	Maryland	United States	21401
83	Marlene and Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland	United States	21201
84	Greater Baltimore Medical Center and Cancer Center	Baltimore	Maryland	United States	21204
85	Harbor Hospital Center	Baltimore	Maryland	United States	21215-1290
86	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
87	St. Agnes Cancer Center	Baltimore	Maryland	United States	21229
88	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
89	Peninsula Regional Medical Center	Salisbury	Maryland	United States	21801
90	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02114
91	Cancer Research Center at Boston Medical Center	Boston	Massachusetts	United States	02118
92	Cape Cod Hospital	Hyannis	Massachusetts	United States	02601
93	Veterans Affairs Medical Center - Boston (Jamaica Plain)	Jamaica Plain	Massachusetts	United States	02130
94	NSMC Cancer Center	Peabody	Massachusetts	United States	01960
95	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
96	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0010
97	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
98	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
99	Hurley Medical Center	Flint	Michigan	United States	48503
100	McLaren Regional Cancer Center	Flint	Michigan	United States	48532-3685
101	CCOP - Kalamazoo	Kalamazoo	Michigan	United States	49007-3731
102	Marquette General Hospital	Marquette	Michigan	United States	49855
103	MidMichigan Medical Center - Midland	Midland	Michigan	United States	48670
104	CCOP - Beaumont	Royal Oak	Michigan	United States	48073-6769
105	William Beaumont Hospital - Royal Oak	Royal Oak	Michigan	United States	48073
106	William Beaumont Hospital - Troy	Troy	Michigan	United States	48085
107	Fairview University Medical Center - University Campus	Minneapolis	Minnesota	United States	55455
108	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905-0001
109	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
110	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
111	CCOP - Kansas City	Kansas City	Missouri	United States	64131
112	St. Louis University Hospital Cancer Center	Saint Louis	Missouri	United States	63110-0250
113	Mallinckrodt Institute of Radiology	Saint Louis	Missouri	United States	63110
114	Cancer Research for the Ozarks	Springfield	Missouri	United States	65807
115	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65807
116	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
117	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
118	Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha	Omaha	Nebraska	United States	68114-4199
119	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-7521
120	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
121	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89109
122	Norris Cotton Cancer Center at Dartmouth Medical School	Lebanon	New Hampshire	United States	03756-0002
123	Elliot Regional Cancer Center	Manchester	New Hampshire	United States	03103
124	Cooper Cancer Institute	Camden	New Jersey	United States	01803
125	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey	United States	07019
126	John F. Kennedy Medical Center	Edison	New Jersey	United States	08818
127	Trinitas Hospital - Jersey Street Campus	Elizabeth	New Jersey	United States	07201
128	Monmouth Medical Center	Long Branch	New Jersey	United States	07740-6395
129	South Jersey Regional Cancer Center	Millville	New Jersey	United States	08332
130	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital	Mount Holly	New Jersey	United States	08060
131	Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
132	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
133	Atlantic City Medical Center	Pomona	New Jersey	United States	08240
134	Medical Center of Princeton	Princeton	New Jersey	United States	08540
135	Valley Hospital	Ridgewood	New Jersey	United States	07450
136	Somerset Medical Center	Somerville	New Jersey	United States	08876
137	Community Medical Center	Toms River	New Jersey	United States	08755
138	Fox Chase Cancer Center at St. Francis Medical Center	Trenton	New Jersey	United States	08629
139	Associated Radiologists, P.A.	Warren	New Jersey	United States	07059
140	Radiation Oncology Associates of Albuquerque	Albuquerque	New Mexico	United States	87109
141	Cancer Center of Albany Medical Center	Albany	New York	United States	12208
142	State University of New York Health Science Center at Brooklyn	Brooklyn	New York	United States	11203
143	New York Methodist Hospital	Brooklyn	New York	United States	11215
144	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
145	Finger Lakes Radiation Oncology Center	Clifton Springs	New York	United States	14432
146	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
147	Beth Israel Medical Center - Philipps Ambulatory Care Center	New York	New York	United States	10003
148	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York	United States	10032
149	Champlain Valley Physicians Hospital Medical Center	Plattsburgh	New York	United States	12901-1490
150	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
151	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York	United States	13217
152	Riverhill Radiation Oncology	Yonkers	New York	United States	10701
153	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
154	Batte Cancer Center at Northeast Medical Center	Concord	North Carolina	United States	28025
155	Leo W. Jenkins Cancer Center of University Health Systems of Eastern Carolina	Greenville	North Carolina	United States	27835-6028
156	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina	United States	27104-4241
157	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1082
158	Trinity Cancer Care Center	Minot	North Dakota	United States	58701
159	Akron General Medical Center	Akron	Ohio	United States	44302
160	Akron City Hospital	Akron	Ohio	United States	44304
161	Cancer Center at Christ Hospital	Cincinnati	Ohio	United States	45219
162	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45219
163	Ireland Cancer Center	Cleveland	Ohio	United States	44106-5065
164	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106
165	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
166	CCOP - Columbus	Columbus	Ohio	United States	43206
167	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio	United States	43210-1240
168	CCOP - Dayton	Dayton	Ohio	United States	45429
169	Parma Community General Hospital	Parma	Ohio	United States	44129
170	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43623-3456
171	Frank C. Love Cancer Institute at St. Anthony Hospital	Oklahoma City	Oklahoma	United States	73102
172	Oklahoma University Medical Center at University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
173	St. John Health System	Tulsa	Oklahoma	United States	74104
174	CCOP - Oklahoma	Tulsa	Oklahoma	United States	74136
175	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
176	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
177	John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital	Allentown	Pennsylvania	United States	18105
178	St. Luke's Hospital Cancer Center	Bethlehem	Pennsylvania	United States	18015
179	Geisinger Medical Center	Danville	Pennsylvania	United States	17822-2001
180	Mercy Fitzgerald Hospital	Darby	Pennsylvania	United States	19023
181	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania	United States	19026
182	Pocono Cancer Center	East Stroudsburg	Pennsylvania	United States	18301
183	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
184	Abramson Cancer Center at University of Pennsylvania Medical Center	Philadelphia	Pennsylvania	United States	19104-4283
185	Veterans Affairs Medical Center - Philadelphia	Philadelphia	Pennsylvania	United States	19104
186	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
187	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
188	Albert Einstein Cancer Center	Philadelphia	Pennsylvania	United States	19141-3098
189	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
190	Mercy Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15219
191	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania	United States	15224
192	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15236
193	Reading Hospital and Medical Center	Reading	Pennsylvania	United States	19612-6052
194	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania	United States	18501
195	Wilkes-Barre General Hospital	Wilkes-Barre	Pennsylvania	United States	18764-0001
196	CCOP - MainLine Health	Wynnewood	Pennsylvania	United States	19096
197	Wellspan Health - York Cancer Center	York	Pennsylvania	United States	17403
198	Roger Williams Medical Center	Providence	Rhode Island	United States	02908-4735
199	CCOP - Greenville	Greenville	South Carolina	United States	29615
200	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
201	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57709
202	West Tennessee Cancer Center at Jackson-Madison County General Hospital	Jackson	Tennessee	United States	38301
203	Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center	Nashville	Tennessee	United States	37232-5671
204	Harrington Cancer Center	Amarillo	Texas	United States	79106
205	Arlington Cancer Center	Arlington	Texas	United States	76012
206	University of Texas Medical Branch	Galveston	Texas	United States	77555-0209
207	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
208	Wilford Hall Medical Center	Lackland Air Force Base	Texas	United States	78236-5300
209	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79410-1894
210	Bayshore Medical Center	Pasadena	Texas	United States	77504
211	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
212	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
213	Dixie Regional Medical Center	Saint George	Utah	United States	84770
214	University of Utah Health Sciences Center	Salt Lake City	Utah	United States	84132
215	LDS Hospital	Salt Lake City	Utah	United States	84143
216	Green Mountain Oncology Group	Bennington	Vermont	United States	05201
217	Vermont Cancer Center at University of Vermont	Burlington	Vermont	United States	05405-0075
218	Cancer Center at the University of Virginia	Charlottesville	Virginia	United States	22908
219	RMH Regional Cancer Center	Harrisonburg	Virginia	United States	22801
220	Naval Medical Center, Portsmouth	Portsmouth	Virginia	United States	23708-2197
221	Bon Secours - St. Mary's Hospital	Richmond	Virginia	United States	23226
222	Massey Cancer Center at Virginia Commonwealth University	Richmond	Virginia	United States	23298-0058
223	Cancer Institute at Virginia Mason Medical Center	Seattle	Washington	United States	98111
224	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195-6043
225	Deaconess Medical Center	Spokane	Washington	United States	99204
226	Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
227	Schiffler Cancer Center	Wheeling	West Virginia	United States	26003
228	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin	United States	54301
229	St. Vincent Hospital	Green Bay	Wisconsin	United States	54307-3508
230	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
231	Southern Wisconsin Radiotherapy Center	Madison	Wisconsin	United States	53713
232	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792
233	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin	United States	54449
234	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
235	Community Memorial Hospital	Menomonee Falls	Wisconsin	United States	53051
236	Columbia Hospital	Milwaukee	Wisconsin	United States	53211
237	St. Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
238	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
239	Veterans Affairs Medical Center - Milwaukee (Zablocki)	Milwaukee	Wisconsin	United States	53295
240	All Saints Cancer Center at All Saints Healthcare	Racine	Wisconsin	United States	53405
241	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin	United States	53188
242	Tom Baker Cancer Center - Calgary	Calgary	Alberta	Canada	T2N 4N2
243	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
244	Doctor Leon Richard Oncology Centre	Moncton	New Brunswick	Canada	E1C 8X3
245	Saint John Regional Hospital	Saint John	New Brunswick	Canada	E2L 4L2
246	Newfoundland Cancer Treatment and Research Foundation	St. Johns	Newfoundland and Labrador	Canada	A1B 3V6
247	Nova Scotia Cancer Centre	Halifax	Nova Scotia	Canada	B3H 1V7
248	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
249	Kingston Regional Cancer Centre	Kingston	Ontario	Canada	K7L 5P9
250	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario	Canada	N6A 4L6
251	Ottawa Regional Cancer Centre	Ottawa	Ontario	Canada	K1H 1C4
252	Northeastern Ontario Regional Cancer Centre - Sudbury	Sudbury	Ontario	Canada	P3E 5J1
253	Northwestern Ontario Regional Cancer Care	Thunder Bay	Ontario	Canada	P7B 6V4
254	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
255	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
256	CHUS-Hopital Fleurimont	Fleurimont	Quebec	Canada	J1H 5N4
257	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec	Canada	H2L 4MI
258	McGill University	Montreal	Quebec	Canada	H2W 1S6
259	Centre Hospitalier Universitaire de Quebec	Quebec City	Quebec	Canada	G1R 2J6
260	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
261	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4

Sponsors and Collaborators

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

Investigators

• Study Chair: Michael G. Haddock, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00005044
• Other Study ID Numbers: RTOG-9910; CDR0000067635
• First Posted: Jan 27, 2003
• Last Update Posted: Jun 15, 2022
• Last Verified: May 1, 2022

• Keywords provided by Radiation Therapy Oncology Group: adenocarcinoma of the prostate; stage IIB prostate cancer; stage IIA prostate cancer; stage III prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Bicalutamide; Flutamide; Hormones; Prolactin Release-Inhibiting Factors

Study Results

Participant Flow

Arm/Group Title	TAS x 8 Weeks	TAS x 28 Weeks
Arm/Group Description	Total Androgen Suppression (TAS) (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by radiation therapy (RT) with concurrent TAS (LHRH agonist and Casodex or Eulexin).	TAS (LHRH agonist and Casodex or Eulexin) x 28 weeks followed by RT with concurrent TAS (LHRH agonist and Casodex or Eulexin).
Period Title: Overall Study
STARTED	790	789
COMPLETED	752	737
NOT COMPLETED	38	52

Baseline Characteristics

Arm/Group Title	TAS x 8 Weeks	TAS x 28 Weeks	Total
Arm/Group Description	Total Androgen Suppression (TAS) (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by radiation therapy (RT) with concurrent TAS (LHRH agonist and Casodex or Eulexin).	TAS (LHRH agonist and Casodex or Eulexin) x 28 weeks followed by RT with concurrent TAS (LHRH agonist and Casodex or Eulexin).	Total of all reporting groups
Overall Participants	752	737	1489
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	71	71	71
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	752 100%	737 100%	1489 100%

Outcome Measures

1. Primary Outcome

Title	Disease-specific Survival (DSS) (10-year Rates Reported)
Description	Disease-specific survival time is measured from date of randomization to death due to prostate cancer based on study chair review, with prostate-cancer death defined as (1) primary cause of death certified as due to prostate cancer, (2) complication of therapy, irrespective of disease status, (3) disease progression in the absence of any anti-tumor therapy, or (4) a 1.0 ng/ml-exceeding-rise in serum prostate-specific antigen (PSA) level on at least two consecutive occasions that occurs during or after salvage androgen suppression therapy. Death due to other causes is considered a competing risk. All others are censored. DSS is estimated using the cumulative incidence method. Ten-year rate is reported.
Time Frame	From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)

Outcome Measure Data

Analysis Population Description

Eligible patients with follow-up data

Arm/Group Title	TAS x 8 Weeks	TAS x 28 Weeks
Arm/Group Description	Total Androgen Suppression (TAS) (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by radiation therapy (RT) with concurrent TAS (LHRH agonist and Casodex or Eulexin).	TAS (LHRH agonist and Casodex or Eulexin) x 28 weeks followed by RT with concurrent TAS (LHRH agonist and Casodex or Eulexin).
Measure Participants	752	737
Number (95% Confidence Interval) [percentage of participants]	95 12.6%	96 13%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAS x 8 Weeks, TAS x 28 Weeks
	Comments	Assuming 40% of deaths in the 8-wk arm from prostate cancer (PC) and that 8-yr DSS would be 79%, 270 PC deaths were required to detect a 33% hazard reduction in the 28-wk arm with 90% power using the log-rank test with a 2-sided significance level of 0.05. Under assumed failure rates, 1,540 patients accrued over 4 years and observed for an additional 6 years were expected to provide the requisite events. This sample accounted for a 10% ineligible/lack-of-data rate and 3 interim analyses.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.48 to 1.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = TAS x 8 weeks

2. Secondary Outcome

Title	Overall Survival (OS) (10-year Rates Reported)
Description	Survival time is defined as time from randomization to the date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Ten-year rate is reported.
Time Frame	From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)

Outcome Measure Data

Analysis Population Description

Eligible patients with follow-up data

Arm/Group Title	TAS x 8 Weeks	TAS x 28 Weeks
Arm/Group Description	Total Androgen Suppression (TAS) (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by radiation therapy (RT) with concurrent TAS (LHRH agonist and Casodex or Eulexin).	TAS (LHRH agonist and Casodex or Eulexin) x 28 weeks followed by RT with concurrent TAS (LHRH agonist and Casodex or Eulexin).
Measure Participants	752	737
Number (95% Confidence Interval) [percentage of participants]	66 8.8%	67 9.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAS x 8 Weeks, TAS x 28 Weeks
	Comments	With 1540 patients accrued over 4 years and observed for an additional 6 years, determined for the primary endpoint, there would be 90% power to detect a 22% reduction in the hazard of all cause deaths in the 28-week arm, with 2-sided significance level of 0.05. This sample accounted for a 10% ineligible/lack-of-data rate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments
	Method	Log Rank
	Comments	2-sided significance level of 0.05
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = TAS x 8 weeks

3. Secondary Outcome

Title	Disease-free Survival (DFS) (10-year Rates Reported)
Description	Disease-free survival time is defined as time from randomization to the date of disease progression or death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Ten-year rate is reported.
Time Frame	From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)

Outcome Measure Data

Analysis Population Description

Eligible patients without follow-up data

Arm/Group Title	TAS x 8 Weeks	TAS x 28 Weeks
Arm/Group Description	Total Androgen Suppression (TAS) (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by radiation therapy (RT) with concurrent TAS (LHRH agonist and Casodex or Eulexin).	TAS (LHRH agonist and Casodex or Eulexin) x 28 weeks followed by RT with concurrent TAS (LHRH agonist and Casodex or Eulexin).
Measure Participants	752	737
Number (95% Confidence Interval) [percentage of participants]	24 3.2%	23 3.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAS x 8 Weeks, TAS x 28 Weeks
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.47
	Comments
	Method	Log Rank
	Comments	Significance level = 0.05
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = TAS x 8 weeks

4. Secondary Outcome

Title	Clinical Patterns of Tumor Recurrence: Time to Locoregional Progression (LRP) and Time to Distant Metastasis (DM) (10 Year Rates Reported)
Description	Time to distant metastasis measured from date of randomization to date of documented distant metastasis; competing risks are BF, LRP, and death without DM; all others are censored. Time to locoregional progression measured from date of randomization to date of documented local or regional progression; competing risks are BF [protocol definition- first of (1) the midway date between the last non-rising PSA and the first rising PSA of three consecutive rises or (2) the date of the initiation of salvage hormone therapy], DM, and death without LRP; all others are censored. LRP and DM are estimated using the cumulative incidence method. Ten -year rates are reported.
Time Frame	From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)

Outcome Measure Data

Analysis Population Description

Eligible patients with follow-up data

Arm/Group Title	TAS x 8 Weeks	TAS x 28 Weeks
Arm/Group Description	Total Androgen Suppression (TAS) (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by radiation therapy (RT) with concurrent TAS (LHRH agonist and Casodex or Eulexin).	TAS (LHRH agonist and Casodex or Eulexin) x 28 weeks followed by RT with concurrent TAS (LHRH agonist and Casodex or Eulexin).
Measure Participants	752	737
Locoregional progression	6 0.8%	4 0.5%
Distant metastasis	6 0.8%	6 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAS x 8 Weeks, TAS x 28 Weeks
	Comments	Locoregional progression
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments
	Method	Gray's test
	Comments	2-sided significance level = 0.05
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; 0.40 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = TAS x 8 weeks

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TAS x 8 Weeks, TAS x 28 Weeks
	Comments	Distant metastasis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.80
	Comments
	Method	Gray's test
	Comments	2-sided significance level = 0.05
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.68 to 1.66
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = TAS x 8 weeks

5. Secondary Outcome

Title	Time to First Biochemical Failure (BF) (10-year Rates Reported)
Description	Protocol definition: Time to BF measured from date of randomization to first of (1) the midway date between the last non-rising PSA and the first rising PSA of three consecutive rises or (2) the date of the initiation of salvage hormone therapy; competing risks are LRP, DM, and death without BF; all others are censored. Phoenix definition: Time to BF measured from date of randomization to first of (1) the date of documented rise of 2 ng/ml above the post-treatment(RT end date) nadir or (2) the date of the initiation of salvage hormone therapy; competing risks are LRP, DM, and death without BF; all others are censored. For both definitions BF is estimated using the cumulative incidence method. Ten year rates reported.
Time Frame	From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)

Outcome Measure Data

Analysis Population Description

Eligible patients with follow-up data

Arm/Group Title	TAS x 8 Weeks	TAS x 28 Weeks
Arm/Group Description	Total Androgen Suppression (TAS) (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by radiation therapy (RT) with concurrent TAS (LHRH agonist and Casodex or Eulexin).	TAS (LHRH agonist and Casodex or Eulexin) x 28 weeks followed by RT with concurrent TAS (LHRH agonist and Casodex or Eulexin).
Measure Participants	752	737
Protocol definition	56 7.4%	59 8%
Phoenix definition	27 3.6%	27 3.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAS x 8 Weeks, TAS x 28 Weeks
	Comments	Protocol definition
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	Gray's test
	Comments	2-sided significance level = 0.05
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = TAS x 8 weeks

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TAS x 8 Weeks, TAS x 28 Weeks
	Comments	Phoenix definition
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments
	Method	Gray's test
	Comments	2-sided significance level = 0.05
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = TAS x 8 weeks

6. Secondary Outcome

Title	Time to Second Biochemical Failure (SBF) (10-year Rates Reported)
Description	Time to SBF measured from date of randomization to the date of PSA increase of ≥1.0 ng/mL (from the nadir PSA after completion of protocol-specified therapy) after salvage androgen suppression was started; competing risks LRP, DM, and death without SBF; all others are censored. SBF is estimated using the cumulative incidence method. Ten-year rates are reported.
Time Frame	From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)

Outcome Measure Data

Analysis Population Description

Eligible patients with follow-up data

Arm/Group Title	TAS x 8 Weeks	TAS x 28 Weeks
Arm/Group Description	Total Androgen Suppression (TAS) (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by radiation therapy (RT) with concurrent TAS (LHRH agonist and Casodex or Eulexin).	TAS (LHRH agonist and Casodex or Eulexin) x 28 weeks followed by RT with concurrent TAS (LHRH agonist and Casodex or Eulexin).
Measure Participants	752	737
Number (95% Confidence Interval) [percentage of participants]	10 1.3%	9 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAS x 8 Weeks, TAS x 28 Weeks
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments
	Method	Log Rank
	Comments	2-sided significance level = 0.05
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.64 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = TAS x 8 weeks

7. Secondary Outcome

Title	Treatment-induced Morbidity (Highest Grade Toxicity Reported Per Patient)
Description	Acute drug therapy and radiation (<= 90 days from start of RT) toxicity was graded using the Common Toxicity Criteria (CTC) v.2.0 criteria; late toxicity was graded using the Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) Late Radiation Morbidity Scoring schema. Grade refers to the severity of the toxicity. The CTC v2.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1 Mild toxicity, Grade 2 Moderate toxicity, Grade 3 Severe toxicity, Grade 4 Life-threatening or disabling toxicity, Grade 5 Death related to toxicity. The highest grade acute and late toxicity was determined for each patient.
Time Frame	From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)

Outcome Measure Data

Analysis Population Description

Eligible patients with adverse event data in corresponding time frame (during hormone therapy and <=90 days from RT start; > 90 days from RT start)

Arm/Group Title	TAS x 8 Weeks	TAS x 28 Weeks
Arm/Group Description	Total Androgen Suppression (TAS) (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by radiation therapy (RT) with concurrent TAS (LHRH agonist and Casodex or Eulexin).	TAS (LHRH agonist and Casodex or Eulexin) x 28 weeks followed by RT with concurrent TAS (LHRH agonist and Casodex or Eulexin).
Measure Participants	747	735
Acute RT and Hormone Toxicity: Grade 1	30.8 4.1%	19.5 2.6%
Acute RT and Hormone Toxicity: Grade 2	41.6 5.5%	49.8 6.8%
Acute RT and Hormone Toxicity: Grade 3	16.1 2.1%	25.7 3.5%
Acute RT and Hormone Toxicity: Grade 4	0 0%	0.1 0%
Acute RT and Hormone Toxicity: Grade 5	0 0%	0 0%
Late RT Toxicity: Grade 1	34.0 4.5%	32.9 4.5%
Late RT Toxicity: Grade 2	20.5 2.7%	22.5 3.1%
Late RT Toxicity: Grade 3	9.7 1.3%	8.0 1.1%
Late RT Toxicity: Grade 4	0.1 0%	0.3 0%
Late RT Toxicity: Grade 5	0 0%	0 0%

Adverse Events

Adverse Event Reporting Description	Eligible patients with adverse event data are included. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Arm/Group Title	TAS x 8 Weeks		TAS x 28 Weeks
Arm/Group Description	Total Androgen Suppression (TAS) (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by radiation therapy (RT) with concurrent TAS (LHRH agonist and Casodex or Eulexin).		TAS (LHRH agonist and Casodex or Eulexin) x 28 weeks followed by RT with concurrent TAS (LHRH agonist and Casodex or Eulexin).
All Cause Mortality
	TAS x 8 Weeks		TAS x 28 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	TAS x 8 Weeks		TAS x 28 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	121/747 (16.2%)		109/735 (14.8%)
Cardiac disorders
Arrhythmia NOS	1/747 (0.1%)		0/735 (0%)
Supraventricular arrhythmia NOS	0/747 (0%)		1/735 (0.1%)
Gastrointestinal disorders
Diarrhea NOS	12/747 (1.6%)		18/735 (2.4%)
Gastritis NOS	0/747 (0%)		1/735 (0.1%)
Late RT Toxicity: Other GI: NOS	10/747 (1.3%)		3/735 (0.4%)
Late RT Toxicity: Small/Large Intestine: NOS	9/747 (1.2%)		8/735 (1.1%)
Proctalgia	0/747 (0%)		1/735 (0.1%)
Proctitis NOS	1/747 (0.1%)		1/735 (0.1%)
Vomiting NOS	1/747 (0.1%)		0/735 (0%)
General disorders
Late RT Toxicity: Other: NOS	24/747 (3.2%)		26/735 (3.5%)
Pain-other	1/747 (0.1%)		0/735 (0%)
Hepatobiliary disorders
Hepatic-Other	0/747 (0%)		1/735 (0.1%)
Infections and infestations
Infection with unknown ANC	0/747 (0%)		1/735 (0.1%)
Infection, Other	0/747 (0%)		1/735 (0.1%)
Injury, poisoning and procedural complications
Dermatitis radiation NOS	1/747 (0.1%)		0/735 (0%)
Investigations
Alanine aminotransferase increased	15/747 (2%)		4/735 (0.5%)
Aspartate aminotransferase increased	4/747 (0.5%)		0/735 (0%)
Blood bilirubin increased	1/747 (0.1%)		0/735 (0%)
Gamma-glutamyltransferase increased	0/747 (0%)		1/735 (0.1%)
Platelet count decreased	0/747 (0%)		1/735 (0.1%)
Metabolism and nutrition disorders
Anorexia	1/747 (0.1%)		0/735 (0%)
Dehydration	1/747 (0.1%)		0/735 (0%)
Hyperglycemia NOS	2/747 (0.3%)		3/735 (0.4%)
Hypoglycaemia NOS	1/747 (0.1%)		0/735 (0%)
Hypokalemia	1/747 (0.1%)		0/735 (0%)
Musculoskeletal and connective tissue disorders
Bone pain	1/747 (0.1%)		0/735 (0%)
Myositis	0/747 (0%)		1/735 (0.1%)
Nervous system disorders
Cerebral ischaemia	0/747 (0%)		1/735 (0.1%)
Headache NOS	0/747 (0%)		1/735 (0.1%)
Peripheral motor neuropathy	1/747 (0.1%)		0/735 (0%)
Syncope	0/747 (0%)		1/735 (0.1%)
Renal and urinary disorders
Dysuria	6/747 (0.8%)		1/735 (0.1%)
Late RT Toxicity: Bladder: NOS	33/747 (4.4%)		24/735 (3.3%)
Renal/GU-Other	1/747 (0.1%)		2/735 (0.3%)
Urinary retention	1/747 (0.1%)		1/735 (0.1%)
Reproductive system and breast disorders
Gynaecomastia	0/747 (0%)		1/735 (0.1%)
Late RT Toxicity: Other GU: NOS	21/747 (2.8%)		25/735 (3.4%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	0/747 (0%)		1/735 (0.1%)
Dyspnea NOS	2/747 (0.3%)		1/735 (0.1%)
Pulmonary-other	0/747 (0%)		1/735 (0.1%)
Skin and subcutaneous tissue disorders
Dermatitis exfoliative NOS	0/747 (0%)		1/735 (0.1%)
Late RT Toxicity: Skin: NOS	0/747 (0%)		1/735 (0.1%)
Vascular disorders
Hypertension NOS	0/747 (0%)		1/735 (0.1%)
Other (Not Including Serious) Adverse Events
	TAS x 8 Weeks		TAS x 28 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	695/747 (93%)		707/735 (96.2%)
Gastrointestinal disorders
Constipation	25/747 (3.3%)		42/735 (5.7%)
Diarrhea NOS	238/747 (31.9%)		245/735 (33.3%)
Late RT Toxicity: Other GI: NOS	135/747 (18.1%)		159/735 (21.6%)
Late RT Toxicity: Small/Large Intestine: NOS	194/747 (26%)		196/735 (26.7%)
Proctitis NOS	173/747 (23.2%)		164/735 (22.3%)
General disorders
Late RT Toxicity: Other: NOS	113/747 (15.1%)		124/735 (16.9%)
Fatigue	159/747 (21.3%)		224/735 (30.5%)
Injury, poisoning and procedural complications
Dermatitis radiation NOS	103/747 (13.8%)		89/735 (12.1%)
Investigations
Alanine aminotransferase increased	92/747 (12.3%)		104/735 (14.1%)
Blood bilirubin increased	30/747 (4%)		41/735 (5.6%)
Psychiatric disorders
Libido decreased	17/747 (2.3%)		51/735 (6.9%)
Renal and urinary disorders
Dysuria	82/747 (11%)		85/735 (11.6%)
Late RT Toxicity: Bladder: NOS	260/747 (34.8%)		270/735 (36.7%)
Urinary frequency	444/747 (59.4%)		456/735 (62%)
Reproductive system and breast disorders
Gynaecomastia	34/747 (4.6%)		107/735 (14.6%)
Impotence	64/747 (8.6%)		132/735 (18%)
Late RT Toxicity: Other GU: NOS	191/747 (25.6%)		194/735 (26.4%)
Vascular disorders
Menopausal symptoms	458/747 (61.3%)		596/735 (81.1%)

Limitations/Caveats

The data monitoring committee decided in June 2012 after the first interim analysis that the trial should be reported early due to the low number of events.

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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.