Hormone Therapy and Radiation Therapy or Hormone Therapy and Radiation Therapy Followed by Docetaxel and Prednisone in Treating Patients With Localized Prostate Cancer

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00288080
• Collaborator: National Cancer Institute (NCI) (NIH), NRG Oncology (Other)
• Enrollment: 612
• Locations: 254
• Arms: 2
• Duration (Months): 197.6
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Androgens can cause the growth of prostate cancer cells. Hormone therapy using drugs, such as leuprolide, goserelin, flutamide, or bicalutamide, may fight prostate cancer by lowering the amount of androgens the body makes. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving hormone therapy and radiation therapy together with chemotherapy is more effective than giving hormone therapy together with radiation therapy in treating prostate cancer.

PURPOSE: This randomized phase III trial is studying hormone therapy and radiation therapy followed by docetaxel and prednisone to see how well it works compared to hormone therapy and radiation therapy in treating patients with localized prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Dexamethasone; Drug: Prednisone; Drug: docetaxel; Drug: Oral antiandrogen; Radiation: Radiation therapy; Drug: LHRH agonist	Phase 3

Detailed Description

OBJECTIVES:

Primary

• Compare the relative efficacy, in terms of overall survival, of the combination of androgen suppression and radiotherapy versus androgen suppression and radiotherapy followed by docetaxel and prednisone in patients with localized, high-risk prostate cancer.

Secondary

• Compare the disease-free survival and incidence of adverse events in patients treated with these regimens.

• Compare the biochemical control, local control, and freedom from distant metastases in patients treated with these regimens.

• Determine the validity of prostate-specific antigen (PSA)-defined endpoints as a surrogate for overall survival of patients treated with these regimens.

• Compare the time interval between biochemical failure and distant metastases with respect to testosterone level in patients treated with these regimens.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to risk group.

• Arm I: Patients receive androgen suppression therapy comprising luteinizing hormone-releasing hormone (LHRH) agonist (e.g., leuprolide acetate, goserelin, buserelin, or triptorelin) and oral antiandrogen (i.e., oral flutamide 3 times daily for 2 months or oral bicalutamide once daily for 2 months). Beginning at week 8, patients undergo radiotherapy 5 days a week for approximately 8 weeks. Antiandrogen therapy is discontinued at completion of radiotherapy, but LHRH agonist therapy continues for 20 months.

• Arm II: Patients receive androgen suppression therapy and undergo radiotherapy as in arm

1. Beginning 4 weeks after completion of radiotherapy, patients receive docetaxel IV over 1 hour on day 1 and oral prednisone daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients continue LHRH agonist therapy as in arm I.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 612 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT Vs AS and 3DCTR/IMRT Followed by Chemotherapy With Docetaxel and Prednisone for Localized, High-Risk, Prostate Cancer
• Study Start Date: Dec 1, 2005
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: May 20, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Androgen suppression + Radiation Therapy Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of radiation therapy (RT).	Drug: Oral antiandrogen; Oral antiandrogen of treating institution's choice to be given per package instructions for 8 weeks, then concurrent with radiation therapy. Treatment is discontinued at the end of radiation therapy.; Radiation: Radiation therapy; 46.8 Gy, using either three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiation therapy (IMRT), will be given to the regional lymphatics followed by a 25.2-28.8 Gy boost to the prostate, to bring the total dose to the prostate to 72.0-75.6 Gy. Daily prescription doses will be 1.8 Gy per day, 5 days per week x 8-8.5 weeks, beginning 8 weeks after the initiation of androgen suppression.; Other Names: 3DCRT Three-dimensional conformal radiotherapy IMRT Intensity-modulated radiation therapy ; Drug: LHRH agonist; LHRH agonist of treating institution's choice to be given per package instructions for 8 weeks, then concurrent with radiation therapy, and then until 24 months from initiation of any treatment has been reached.
Experimental: Androgen suppression + Radiation Therapy + Chemotherapy Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT. Following completion of RT, 6 cycles of docetaxel (premedicated with dexamethasone) and prednisone are delivered concurrently with androgen suppression.	Drug: Dexamethasone; Premedication of dexamethasone prior to docetaxel, per institutional standards.; Drug: Prednisone; 10 mg orally per day until day 21 of the last cycle of docetaxel, beginning 28 days after the completion of RT.; Drug: docetaxel; 75 mg/m2 i.v. over 1 hour (on day 1 of each cycle) every 21 days for 6 cycles, beginning 28 days after the completion of RT.; Drug: Oral antiandrogen; Oral antiandrogen of treating institution's choice to be given per package instructions for 8 weeks, then concurrent with radiation therapy. Treatment is discontinued at the end of radiation therapy.; Radiation: Radiation therapy; 46.8 Gy, using either three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiation therapy (IMRT), will be given to the regional lymphatics followed by a 25.2-28.8 Gy boost to the prostate, to bring the total dose to the prostate to 72.0-75.6 Gy. Daily prescription doses will be 1.8 Gy per day, 5 days per week x 8-8.5 weeks, beginning 8 weeks after the initiation of androgen suppression.; Other Names: 3DCRT Three-dimensional conformal radiotherapy IMRT Intensity-modulated radiation therapy ; Drug: LHRH agonist; LHRH agonist of treating institution's choice to be given per package instructions for 8 weeks, then concurrent with radiation therapy, and then until 24 months from initiation of any treatment has been reached.

Outcome Measures

Primary Outcome Measures

1. Overall Survival [From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.]

   Four-year rates are shown. Survival time is defined as time from randomization to 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.

Secondary Outcome Measures

1. Biochemical Control [From randomization to date of biochemical failure, death, or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.]

   Four-year rates are shown (Kaplan-Meier estimates). Biochemical control is defined as freedom from biochemical failure. Biochemical failure was considered as the first of either prostate-specific antigen (PSA) failure or initiation of salvage hormone therapy. PSA failure was defined as a rise of 2 ng/ml over the nadir PSA. Patients who experienced death without biochemical failure, local failure prior to biochemical failure, or development of distant metastases prior to biochemical failure were censored on the date of the competing event. The corresponding outcome time was measured from the date of randomization.

2. Local Control [From randomization to date of local failure, death, or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.]

   Local control is defined as the absence of local failure which is the first of either progression or recurrence within the prostate. Progression of the tumor was considered to have occurred when there was a 25% or greater increase in the product of the two largest perpendicular diameters of the prostate. Recurrence was defined as the reappearance of disease after a complete response. Patients who experienced death without local failure, biochemical failure prior to local failure, and development of distant metastases prior to local failure were censored on the date of the competing event. The corresponding outcome time was measured from the date of randomization. Due to an insufficient number of events (2 in each arm), this endpoint was not statistically compared. Local control rates at 4 years were calculated using the Kaplan-Meier method.

3. Distant Metastasis [From randomization to date of distant metastasis, death, or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.]

   Distant failure was considered when there was evidence of metastatic disease. Patients who experienced death without distant failure, local failure prior to distant failure, and biochemical failure prior to distant failure were censored on the date of the competing event. The corresponding outcome time was measured from the date of randomization. Distant failure rates at 4 year were calculated using the Kaplan-Meier method.

4. Disease-free Survival [From randomization to date of progression, death, or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.]

   A failure for disease-free survival is the first of the following: biochemical failure, local failure, distant metastases, or death due to any cause. The corresponding outcome time was measured from the date of randomization. Disease-free survival rates at 4 years were calculated using the Kaplan-Meier method.

5. Incidence of Adverse Events [From start of treatment until the end of follow-up]

   Adverse events are graded using CTCAE v3.0. The worst grade of all adverse events for each patient is counted.

6. The Time Interval Between Biochemical Failure and Distant Failure Respect to Testosterone Level [From date of biochemical failure to development of distant metastasis. Maximum follow-up was 12.9 years.]

   Biochemical failure is defined as the first of either prostate-specific antigen (PSA) failure or the initiation of salvage hormone therapy. PSA failure is defined as a rise in PSA of 2 ng/ml over the nadir PSA. Distant failure is defined as the first occurrence of distant metastasis.

7. Validity of PSA Endpoint as a Surrogate for Overall Survival [From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.]

   Prentice's operational criteria for determining whether determining whether biochemical failure (surrogate endpoint) is a suitable endpoint for overall survival (true endpoint): Treatment is prognostic for true endpoint Treatment is prognostic for surrogate endpoint Surrogate is prognostic for true endpoint The full effect of the treatment on the true endpoint is explained by the surrogate. If any of the criteria are not met, it is concluded that biochemical failure is not a suitable surrogate for overall survival. Therefore, if any of the criteria are met, the other criteria do not do not need to be evaluated.

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically confirmed prostate cancer at high-risk for recurrence within the past 180 days as determined by 1 of the following combinations (risk groups):

• Gleason score ≥ 9, prostate-specific antigen (PSA) ≤ 150 ng/mL, and any T stage

• Gleason score 8, PSA < 20 ng/mL, and stage ≥ T2

• Gleason score 8, PSA 20-150 ng/mL, and any T stage

• Gleason score 7, PSA 20-150 ng/mL, and any T stage

• Clinically negative lymph nodes by imaging (pelvic CT scan or pelvic MRI), nodal sampling, or dissection within 90 days prior to study entry

• Equivocal or questionable lymph nodes ≤ 1.5 cm by imaging allowed

• Positive lymph nodes by capromab pendetide (ProstaScint^®) scan with a corresponding lymph node ≤ 1.5 cm by CT scan or MRI allowed

• PSA ≤ 150 ng/mL

• Cannot have been obtained during any of the following time points:

• 10-day period after prostate biopsy

• After initiation of hormonal therapy

• Within 30 days after discontinuation of finasteride

• Within 90 days after discontinuation of dutasteride

• No distant metastases by physical exam and bone scan

• Equivocal bone scan findings allowed if plain films are negative

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1

• Platelet count ≥ 100,000/mm^3

• Absolute neutrophil count ≥ 1,800/mm^3

• Hemoglobin ≥ 8 g/dL (transfusion or other intervention allowed)

• Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 times upper limit of normal (ULN)

• Alkaline phosphatase ≤ 2.5 times ULN

• Bilirubin ≤ 1.5 times ULN

• Fertile patients must use effective contraception during and for at least 3 months after completion of study treatment

• No prior invasive malignancy, except nonmelanomatous skin cancer or other malignancy, unless disease-free for ≥ 3 years (e.g., carcinoma in situ of the oral cavity or bladder are allowed)

• No unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months

• No transmural myocardial infarction within the past 6 months

• No acute bacterial or fungal infection requiring intravenous antibiotics

• No AIDS

• No prior allergic reaction to any study drugs or other drugs formulated with polysorbate 80

• No existing peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

• At least 60 days since prior 5-alpha reductase inhibitor (e.g., finasteride) for prostatic hypertrophy

• At least 90 days since prior testosterone

• Prior pharmacologic androgen ablation for prostate cancer allowed provided androgen ablation was initiated no more than 50 days prior to study entry

• No prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral orchiectomy

• No prior systemic chemotherapy for prostate cancer

• Prior chemotherapy for a different cancer is allowed

• No prior radiotherapy, including brachytherapy, to the region of prostate cancer that would result in overlap of radiotherapy fields

• Intensity modulated radiotherapy allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB Comprehensive Cancer Center	Birmingham	Alabama	United States	35294
2	Providence Cancer Center	Anchorage	Alaska	United States	99508
3	Arizona Oncology Services Foundation	Phoenix	Arizona	United States	85013
4	Arizona Oncology - Tucson	Tucson	Arizona	United States	85704
5	Auburn Radiation Oncology	Auburn	California	United States	95603
6	Providence Saint Joseph Medical Center - Burbank	Burbank	California	United States	91505
7	Radiation Oncology Centers - Cameron Park	Cameron Park	California	United States	95682
8	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California	United States	95608
9	Enloe Cancer Center at Enloe Medical Center	Chico	California	United States	95926
10	Cancer Care Center at John Muir Health - Concord Campus	Concord	California	United States	94524-4110
11	Washington Township Hospital	Fremont	California	United States	94538
12	Sierra Nevada Cancer Center at Sierra Nevada Memorial Hospital	Grass Valley	California	United States	95945
13	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
14	Memorial Medical Center	Modesto	California	United States	95355
15	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609
16	Lucy Curci Cancer Center at Eisenhower Memorial Hospital and Medical Center	Rancho Mirage	California	United States	92270
17	Radiation Oncology Center - Roseville	Roseville	California	United States	95661
18	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California	United States	95815
19	University of California Davis Cancer Center	Sacramento	California	United States	95817
20	Mercy General Hospital	Sacramento	California	United States	95819
21	California Pacific Medical Center - California Campus	San Francisco	California	United States	94118
22	Torrance Memorial Medical Center	Torrance	California	United States	90509
23	Solano Radiation Oncology Center	Vacaville	California	United States	95687
24	John Muir/Mt. Diablo Comprehensive Cancer Center	Walnut Creek	California	United States	94598
25	Rocky Mountain Cancer Centers - Aurora	Aurora	Colorado	United States	80012
26	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado	United States	80045
27	Swedish Medical Center	Englewood	Colorado	United States	80110
28	Poudre Valley Radiation Oncology	Fort Collins	Colorado	United States	80528
29	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado	United States	81502
30	North Colorado Medical Center	Greeley	Colorado	United States	80631
31	McKee Medical Center	Loveland	Colorado	United States	80539
32	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
33	St. Vincent's Medical Center	Bridgeport	Connecticut	United States	06606
34	Bridgeport Hospital	Bridgeport	Connecticut	United States	06610
35	Hospital of Saint Raphael	New Haven	Connecticut	United States	06511
36	Yale Cancer Center	New Haven	Connecticut	United States	06520-8028
37	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
38	William W. Backus Hospital	Norwich	Connecticut	United States	06360
39	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
40	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610-0232
41	Bay Medical	Panama City	Florida	United States	32401
42	Georgia Cancer Center for Excellence at Grady Memorial Hospital	Atlanta	Georgia	United States	30303
43	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
44	John B. Amos Cancer Center	Columbus	Georgia	United States	31904
45	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
46	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia	United States	31403-3089
47	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
48	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
49	Northwest Community Hospital	Arlington Heights	Illinois	United States	60005
50	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
51	Elmhurst Memorial Hospital	Elmhurst	Illinois	United States	60126
52	Advocate Lutheran General Cancer Care Center	Park Ridge	Illinois	United States	60068-1174
53	Center for Cancer Care at OSF Saint Anthony Medical Center	Rockford	Illinois	United States	61108
54	Cancer Institute at St. John's Hospital	Springfield	Illinois	United States	62702
55	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
56	Saint John's Cancer Center at Saint John's Medical Center	Anderson	Indiana	United States	46016
57	Radiation Oncology Associates Southwest	Fort Wayne	Indiana	United States	46804
58	Parkview Regional Cancer Center at Parkview Health	Fort Wayne	Indiana	United States	46805
59	Veterans Affairs Medical Center - Indianapolis	Indianapolis	Indiana	United States	46202
60	Central Indiana Cancer Centers - East	Indianapolis	Indiana	United States	46219
61	McFarland Clinic, PC	Ames	Iowa	United States	50010
62	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1002
63	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
64	Kansas City Cancer Centers - Southwest	Overland Park	Kansas	United States	66210
65	Norton Suburban Hospital	Louisville	Kentucky	United States	40207
66	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana	United States	71315-3198
67	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
68	Maine Center for Cancer Medicine and Blood Disorders - Scarborough	Scarborough	Maine	United States	04074
69	DeCesaris Cancer Institute at Anne Arundel Medical Center	Annapolis	Maryland	United States	21401
70	St. Agnes Hospital Cancer Center	Baltimore	Maryland	United States	21229
71	Suburban Hospital	Bethesda	Maryland	United States	20814
72	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
73	Hudner Oncology Center at Saint Anne's Hospital - Fall River	Fall River	Massachusetts	United States	02721
74	Shields Radiation Oncology Center - Mansfield	Mansfield	Massachusetts	United States	02048
75	NSMC Cancer Center - Peabody	Peabody	Massachusetts	United States	01960
76	South Suburban Oncology Center	Quincy	Massachusetts	United States	02169
77	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
78	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
79	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
80	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
81	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
82	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan	United States	48910
83	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
84	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
85	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
86	St. Luke's Hospital Cancer Care Center	Duluth	Minnesota	United States	55805
87	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
88	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
89	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
90	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
91	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
92	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
93	United Hospital	Saint Paul	Minnesota	United States	55102
94	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
95	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi	United States	39581
96	Cancer Institute of Cape Girardeau, LLC	Cape Girardeau	Missouri	United States	63703
97	St. John's Regional Medical Center	Joplin	Missouri	United States	64804
98	Kansas City Cancer Centers - South	Kansas City	Missouri	United States	64131
99	Kansas City Cancer Centers - North	Kansas City	Missouri	United States	64154
100	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri	United States	63110
101	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri	United States	63141
102	St. John's Regional Health Center	Springfield	Missouri	United States	65804
103	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
104	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
105	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
106	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
107	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
108	Methodist Estabrook Cancer Center	Omaha	Nebraska	United States	68114
109	Immanuel Medical Center	Omaha	Nebraska	United States	68122
110	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
111	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
112	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
113	Nevada Cancer Institute	Las Vegas	Nevada	United States	89135
114	Dartmouth - Hitchcock Concord	Concord	New Hampshire	United States	03301
115	Seacoast Cancer Center at Wentworth - Douglass Hospital	Dover	New Hampshire	United States	03820
116	Center for Cancer Care at Exeter Hospital	Exeter	New Hampshire	United States	03833
117	Kingsbury Center for Cancer Care at Cheshire Medical Center	Keene	New Hampshire	United States	03431
118	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
119	Elliot Regional Cancer Center at Elliot Hospital	Manchester	New Hampshire	United States	03103
120	Cancer Institute of New Jersey at Cooper University Hospital - Camden	Camden	New Jersey	United States	08103
121	CentraState Medical Center	Freehold	New Jersey	United States	07728
122	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey	United States	08053
123	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08901
124	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
125	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
126	Lovelace Medical Center - Downtown	Albuquerque	New Mexico	United States	87102
127	New Mexico Cancer Center	Albuquerque	New Mexico	United States	87109
128	Radiation Oncology Associates, PA	Albuquerque	New Mexico	United States	87109
129	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
130	Cancer Institute of New Mexico	Santa Fe	New Mexico	United States	87505
131	New York Oncology Hematology, PC at Albany Regional Cancer Care	Albany	New York	United States	12206
132	Bassett Healthcare Regional Cancer Program at Mary Imogene Bassett Hospital	Cooperstown	New York	United States	13326
133	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
134	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
135	Veterans Affairs Medical Center - Syracuse	Syracuse	New York	United States	13210
136	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
137	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
138	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
139	CaroMont Cancer Center at Gaston Memorial Hospital	Gastonia	North Carolina	United States	28053
140	Leo W. Jenkins Cancer Center at ECU Medical School	Greenville	North Carolina	United States	27834
141	High Point Regional Hospital	High Point	North Carolina	United States	27261
142	New Hanover Radiation Oncology, PA	Wilmington	North Carolina	United States	28401
143	Forsyth Regional Cancer Center at Forsyth Medical Center	Winston-Salem	North Carolina	United States	27103
144	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
145	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
146	Barberton Citizens Hospital	Barberton	Ohio	United States	44203
147	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267
148	Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio	United States	44111
149	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
150	Grandview Hospital	Dayton	Ohio	United States	45405
151	Good Samaritan Hospital	Dayton	Ohio	United States	45406
152	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
153	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
154	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
155	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
156	Cleveland Clinic Cancer Center	Independence	Ohio	United States	44131
157	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
158	Lima Memorial Hospital	Lima	Ohio	United States	45804
159	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537-1839
160	Hillcrest Cancer Center at Hillcrest Hospital	Mayfield Heights	Ohio	United States	44124
161	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
162	Cancer Care Center, Incorporated	Salem	Ohio	United States	44460
163	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
164	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
165	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
166	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
167	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
168	Cancer Treatment Center	Wooster	Ohio	United States	44691
169	Cleveland Clinic - Wooster	Wooster	Ohio	United States	44691
170	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
171	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma	United States	73104
172	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma	United States	74136
173	Willamette Valley Cancer Center - Eugene	Eugene	Oregon	United States	97401
174	Knight Cancer Institute at Oregon Health and Science University	Portland	Oregon	United States	97239-3098
175	Salem Hospital Regional Cancer Care Services	Salem	Oregon	United States	97309-5014
176	Celilo Cancer Center at Mid-Columbia Medical Center	The Dalles	Oregon	United States	97058
177	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
178	UPMC Cancer Center at Beaver Medical Center	Beaver	Pennsylvania	United States	15009
179	UPMC Cancer Center at Jefferson Regional Medical Center	Clairton	Pennsylvania	United States	15025
180	Cancer Center at Clarion Hospital	Clarion	Pennsylvania	United States	16214
181	Mercy Fitzgerald Hospital	Darby	Pennsylvania	United States	19023
182	Delaware County Regional Cancer Center at Delaware County Memorial Hospital	Drexel Hill	Pennsylvania	United States	19026
183	Northeast Radiation Oncology Center	Dunmore	Pennsylvania	United States	18512
184	UPMC Cancer Center - Arnold Palmer Pavilion	Greensburg	Pennsylvania	United States	15601
185	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
186	UPMC Cancer Center at the John P. Murtha Pavilion	Johnstown	Pennsylvania	United States	15901
187	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania	United States	15132
188	UPMC - Moon	Moon	Pennsylvania	United States	15108
189	UPMC Cancer Center - Natrona Heights	Natrona Heights	Pennsylvania	United States	15065
190	Jameson Memorial Hospital - North Campus	New Castle	Pennsylvania	United States	16105
191	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301-1792
192	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
193	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania	United States	19111-2497
194	UPMC - Shadyside	Pittsburgh	Pennsylvania	United States	15213-2582
195	UPMC Cancer Center at Magee-Womens Hospital	Pittsburgh	Pennsylvania	United States	15213
196	UPMC Cancer Center at UPMC Presbyterian	Pittsburgh	Pennsylvania	United States	15213
197	UPMC Cancer Center at UPMC St. Margaret	Pittsburgh	Pennsylvania	United States	15215
198	UPMC Cancer Center at UPMC Passavant	Pittsburgh	Pennsylvania	United States	15237
199	UPMC Cancer Center - Upper St. Clair	Pittsburgh	Pennsylvania	United States	15243
200	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania	United States	19612-6052
201	Guthrie Cancer Center at Guthrie Clinic Sayre	Sayre	Pennsylvania	United States	18840
202	Grand View Hospital	Sellersville	Pennsylvania	United States	18960
203	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania	United States	16346
204	UPMC Cancer Center - Uniontown	Uniontown	Pennsylvania	United States	15401
205	Washington Hospital Cancer Center	Washington	Pennsylvania	United States	15301
206	CCOP - Main Line Health	Wynnewood	Pennsylvania	United States	19096
207	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania	United States	19096
208	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania	United States	17405
209	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
210	CCOP - Greenville	Greenville	South Carolina	United States	29615
211	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
212	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
213	Texas Oncology, PA at Harris Center HEB	Bedford	Texas	United States	76022
214	St. Joseph Regional Cancer Center	Bryan	Texas	United States	77802
215	Medical City Dallas Hospital	Dallas	Texas	United States	75230
216	Texas Oncology, PA at Texas Cancer Center Dallas Southwest	Dallas	Texas	United States	75237
217	Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital	Fort Worth	Texas	United States	76104
218	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
219	Texas Oncology, PA at Texas Cancer Center - Sherman	Sherman	Texas	United States	75090
220	Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land	Sugar Land	Texas	United States	77479
221	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah	United States	84157
222	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah	United States	84403
223	Dixie Regional Medical Center - East Campus	Saint George	Utah	United States	84770
224	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah	United States	84112
225	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05401
226	Community Cancer Center at Rutland Regional Medical Center	Rutland	Vermont	United States	05701
227	Naval Medical Center - Portsmouth	Portsmouth	Virginia	United States	23708-2197
228	Veterans Affairs Medical Center - Richmond	Richmond	Virginia	United States	23249
229	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia	United States	23298-0037
230	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington	United States	99204
231	CCOP - Northwest	Tacoma	Washington	United States	98405
232	Madigan Army Medical Center - Tacoma	Tacoma	Washington	United States	98431
233	West Virginia University Health Sciences Center - Charleston	Charleston	West Virginia	United States	25304
234	Theda Care Cancer Institute	Appleton	Wisconsin	United States	54911
235	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
236	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
237	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin	United States	54601
238	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
239	Community Memorial Hospital Cancer Care Center	Menomonee Falls	Wisconsin	United States	53051
240	Columbia Saint Mary's Hospital - Ozaukee	Mequon	Wisconsin	United States	53097
241	Columbia-Saint Mary's Cancer Care Center	Milwaukee	Wisconsin	United States	53211
242	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
243	Veterans Affairs Medical Center - Milwaukee	Milwaukee	Wisconsin	United States	53295
244	Vince Lombardi Cancer Clinic - Sheboygan	Sheboygan	Wisconsin	United States	53081
245	University of Wisconcin Cancer Center at Aspirus Wausau Hospital	Wausau	Wisconsin	United States	54401
246	Tom Baker Cancer Centre - Calgary	Calgary	Alberta	Canada	T2N 4N2
247	Cross Cancer Institute at University of Alberta	Edmonton	Alberta	Canada	T6G 1Z2
248	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
249	London Regional Cancer Program at London Health Sciences Centre	London	Ontario	Canada	N6A 4L6
250	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario	Canada	K1Y 4K7
251	Hopital Notre-Dame du CHUM	Montreal	Quebec	Canada	H2L 4M1
252	McGill Cancer Centre at McGill University	Montreal	Quebec	Canada	H2W 1S6
253	Centre Hospitalier Universitaire de Quebec	Quebec City	Quebec	Canada	G1R 2J6
254	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan	Canada	S4T 7T1

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Howard M. Sandler, MD, University of Michigan Rogel Cancer Center
• Study Chair: Seth Rosenthal, MD, Radiological Associates of Sacramento Medical Group at Sutter Cancer Center
• Study Chair: Mahul Amin, MD, Cedars-Sinai Medical Center
• Study Chair: Leonard G. Gomella, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University
• Study Chair: James Purdy, PhD, University of California, Davis
• Study Chair: Jeff Michalski, MD, Washington University School of Medicine
• Study Chair: Mark Garzotto, MD, Portland VA Medical Center
• Study Chair: Oliver Sartor, MD, Tulane School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00288080
• Other Study ID Numbers: RTOG-0521; CDR0000462375; NCI-2009-00728
• First Posted: Feb 7, 2006
• Last Update Posted: Jun 21, 2022
• Last Verified: May 1, 2022

• Keywords provided by Radiation Therapy Oncology Group: stage III prostate cancer; stage IIB prostate cancer; stage IIA prostate cancer; stage IV prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Dexamethasone; Prednisone; Docetaxel; Androgen Antagonists

Study Results

Participant Flow

Arm/Group Title	Androgen Suppression + Radiation Therapy (RT)	Androgen Suppression + Radiation Therapy + Chemotherapy
Arm/Group Description	Androgen suppression (AS; luteinizing hormone-releasing hormone (LHRH) agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT.	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT. Following completion of RT, 6 cycles of docetaxel (premedicated with dexamethasone) and prednisone are delivered concurrently with androgen suppression.
Period Title: Overall Study
STARTED	307	305
COMPLETED	281	282
NOT COMPLETED	26	23

Baseline Characteristics

Arm/Group Title	Androgen Suppression + Radiation Therapy	Androgen Suppression + Radiation Therapy + Chemotherapy	Total
Arm/Group Description	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT.	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT. Following completion of RT, 6 cycles of docetaxel (premedicated with dexamethasone) and prednisone are delivered concurrently with androgen suppression.	Total of all reporting groups
Overall Participants	281	282	563
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	66	66	66
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	281 100%	282 100%	563 100%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Four-year rates are shown. Survival time is defined as time from randomization to 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.
Time Frame	From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.

Outcome Measure Data

Analysis Population Description

Eligible patients who did not withdraw consent.

Arm/Group Title	Androgen Suppression + Radiation Therapy	Androgen Suppression + Radiation Therapy + Chemotherapy
Arm/Group Description	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT.	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT. Following completion of RT, 6 cycles of docetaxel (premedicated with dexamethasone) and prednisone are delivered concurrently with androgen suppression.
Measure Participants	281	282
Number (95% Confidence Interval) [percentage of participants]	88.7 31.6%	93.3 33.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Androgen Suppression + Radiation Therapy, Androgen Suppression + Radiation Therapy + Chemotherapy
	Comments	The study was designed to detect an improvement in the 4-year overall survival rate from 86% (AS+RT) to 93% (AS+RT+CT). Assuming an exponential survival distribution for each arm, then an absolute improvement of 7% in the 4-year overall survival rate translates to a 51% relative reduction (hazard ratio 0.49) in the yearly death rate. Under a 1-sided significance level of 0.05 and 90% power, at least 78 deaths and 486 cases were required to perform the primary endpoint analysis.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0398
	Comments
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Biochemical Control
Description	Four-year rates are shown (Kaplan-Meier estimates). Biochemical control is defined as freedom from biochemical failure. Biochemical failure was considered as the first of either prostate-specific antigen (PSA) failure or initiation of salvage hormone therapy. PSA failure was defined as a rise of 2 ng/ml over the nadir PSA. Patients who experienced death without biochemical failure, local failure prior to biochemical failure, or development of distant metastases prior to biochemical failure were censored on the date of the competing event. The corresponding outcome time was measured from the date of randomization.
Time Frame	From randomization to date of biochemical failure, death, or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.

Outcome Measure Data

Analysis Population Description

Eligible patients who did not withdraw consent.

Arm/Group Title	Androgen Suppression + Radiation Therapy	Androgen Suppression + Radiation Therapy + Chemotherapy
Arm/Group Description	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT.	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT. Following completion of RT, 6 cycles of docetaxel (premedicated with dexamethasone) and prednisone are delivered concurrently with androgen suppression.
Measure Participants	281	282
Number (95% Confidence Interval) [percentage of participants]	82.0 29.2%	84.1 29.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Androgen Suppression + Radiation Therapy, Androgen Suppression + Radiation Therapy + Chemotherapy
	Comments	Biochemical control rates at 4 years were calculated using the Kaplan-Meier method and compared by a two-sided log-rank test with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Local Control
Description	Local control is defined as the absence of local failure which is the first of either progression or recurrence within the prostate. Progression of the tumor was considered to have occurred when there was a 25% or greater increase in the product of the two largest perpendicular diameters of the prostate. Recurrence was defined as the reappearance of disease after a complete response. Patients who experienced death without local failure, biochemical failure prior to local failure, and development of distant metastases prior to local failure were censored on the date of the competing event. The corresponding outcome time was measured from the date of randomization. Due to an insufficient number of events (2 in each arm), this endpoint was not statistically compared. Local control rates at 4 years were calculated using the Kaplan-Meier method.
Time Frame	From randomization to date of local failure, death, or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.

Outcome Measure Data

Analysis Population Description

Eligible patients who did not withdraw consent

Arm/Group Title	Androgen Suppression + Radiation Therapy	Androgen Suppression + Radiation Therapy + Chemotherapy
Arm/Group Description	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT.	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT. Following completion of RT, 6 cycles of docetaxel (premedicated with dexamethasone) and prednisone are delivered concurrently with androgen suppression.
Measure Participants	281	282
Number (95% Confidence Interval) [percentage of participants]	99.2 35.3%	99.5 35.3%

4. Secondary Outcome

Title	Distant Metastasis
Description	Distant failure was considered when there was evidence of metastatic disease. Patients who experienced death without distant failure, local failure prior to distant failure, and biochemical failure prior to distant failure were censored on the date of the competing event. The corresponding outcome time was measured from the date of randomization. Distant failure rates at 4 year were calculated using the Kaplan-Meier method.
Time Frame	From randomization to date of distant metastasis, death, or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.

Outcome Measure Data

Analysis Population Description

Eligible patients who did not withdraw consent.

Arm/Group Title	Androgen Suppression + Radiation Therapy	Androgen Suppression + Radiation Therapy + Chemotherapy
Arm/Group Description	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT.	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT. Following completion of RT, 6 cycles of docetaxel (premedicated with dexamethasone) and prednisone are delivered concurrently with androgen suppression.
Measure Participants	281	282
Number (95% Confidence Interval) [percentage of participants]	2.6 0.9%	1.9 0.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Androgen Suppression + Radiation Therapy, Androgen Suppression + Radiation Therapy + Chemotherapy
	Comments	Distant failure rates at 4 years were calculated using the Kaplan-Meier method and compared by a two-side log-rank test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	Log Rank
	Comments

5. Secondary Outcome

Title	Disease-free Survival
Description	A failure for disease-free survival is the first of the following: biochemical failure, local failure, distant metastases, or death due to any cause. The corresponding outcome time was measured from the date of randomization. Disease-free survival rates at 4 years were calculated using the Kaplan-Meier method.
Time Frame	From randomization to date of progression, death, or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.

Outcome Measure Data

Analysis Population Description

Eligible patients who did not withdraw consent.

Arm/Group Title	Androgen Suppression + Radiation Therapy	Androgen Suppression + Radiation Therapy + Chemotherapy
Arm/Group Description	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT.	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT. Following completion of RT, 6 cycles of docetaxel (premedicated with dexamethasone) and prednisone are delivered concurrently with androgen suppression.
Measure Participants	281	282
Number (95% Confidence Interval) [percentage of participants]	73.0 26%	78.5 27.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Androgen Suppression + Radiation Therapy, Androgen Suppression + Radiation Therapy + Chemotherapy
	Comments	Disease-free survival rates were compared by a two-sided log-rank test at a significance level of 0.05.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0484
	Comments
	Method	Log Rank
	Comments

6. Secondary Outcome

Title	Incidence of Adverse Events
Description	Adverse events are graded using CTCAE v3.0. The worst grade of all adverse events for each patient is counted.
Time Frame	From start of treatment until the end of follow-up

Outcome Measure Data

Analysis Population Description

Eligible patients who started protocol treatment and did not withdraw consent

Arm/Group Title	Androgen Suppression + Radiation Therapy	Androgen Suppression + Radiation Therapy + Chemotherapy
Arm/Group Description	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT.	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT. Following completion of RT, 6 cycles of docetaxel (premedicated with dexamethasone) and prednisone are delivered concurrently with androgen suppression.
Measure Participants	281	282
Grade 1	14.9 5.3%	2.1 0.7%
Grade 2	48.4 17.2%	25.9 9.2%
Grade 3	26.0 9.3%	40.1 14.2%
Grade 4	4.3 1.5%	28.4 10.1%
Grade 5	1.4 0.5%	0.7 0.2%

7. Secondary Outcome

Title	The Time Interval Between Biochemical Failure and Distant Failure Respect to Testosterone Level
Description	Biochemical failure is defined as the first of either prostate-specific antigen (PSA) failure or the initiation of salvage hormone therapy. PSA failure is defined as a rise in PSA of 2 ng/ml over the nadir PSA. Distant failure is defined as the first occurrence of distant metastasis.
Time Frame	From date of biochemical failure to development of distant metastasis. Maximum follow-up was 12.9 years.

Outcome Measure Data

Analysis Population Description

The analysis will not be done because testosterone measurement dates were not collected.

Arm/Group Title	Androgen Suppression + Radiation Therapy	Androgen Suppression + Radiation Therapy + Chemotherapy
Arm/Group Description	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT.	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT. Following completion of RT, 6 cycles of docetaxel (premedicated with dexamethasone) and prednisone are delivered concurrently with androgen suppression.
Measure Participants	0	0

8. Secondary Outcome

Title	Validity of PSA Endpoint as a Surrogate for Overall Survival
Description	Prentice's operational criteria for determining whether determining whether biochemical failure (surrogate endpoint) is a suitable endpoint for overall survival (true endpoint): Treatment is prognostic for true endpoint Treatment is prognostic for surrogate endpoint Surrogate is prognostic for true endpoint The full effect of the treatment on the true endpoint is explained by the surrogate. If any of the criteria are not met, it is concluded that biochemical failure is not a suitable surrogate for overall survival. Therefore, if any of the criteria are met, the other criteria do not do not need to be evaluated.
Time Frame	From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.

Outcome Measure Data

Analysis Population Description

Because the second criterion is not met, further analysis was not performed.

Arm/Group Title	Androgen Suppression + Radiation Therapy	Androgen Suppression + Radiation Therapy + Chemotherapy
Arm/Group Description	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT.	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT. Following completion of RT, 6 cycles of docetaxel (premedicated with dexamethasone) and prednisone are delivered concurrently with androgen suppression.
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	Participants who started protocol treatment.
Arm/Group Title	Androgen Suppression + Radiation Therapy		Androgen Suppression + Radiation Therapy + Chemotherapy
Arm/Group Description	Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT.		Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT. Following completion of RT, 6 cycles of docetaxel (premedicated with dexamethasone) and prednisone are delivered concurrently with androgen suppression.
All Cause Mortality
	Androgen Suppression + Radiation Therapy		Androgen Suppression + Radiation Therapy + Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Androgen Suppression + Radiation Therapy		Androgen Suppression + Radiation Therapy + Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/302 (8.6%)		93/302 (30.8%)
Blood and lymphatic system disorders
Febrile neutropenia	0/302 (0%)		12/302 (4%)
Hemoglobin	0/302 (0%)		10/302 (3.3%)
Cardiac disorders
Angina pectoris	0/302 (0%)		1/302 (0.3%)
Atrial fibrillation	0/302 (0%)		3/302 (1%)
Cardiac general - Other	1/302 (0.3%)		3/302 (1%)
Myocardial ischemia	6/302 (2%)		5/302 (1.7%)
Myocarditis NOS	0/302 (0%)		1/302 (0.3%)
Ventricular arrhythmia NOS	0/302 (0%)		2/302 (0.7%)
Gastrointestinal disorders
Abdominal pain NOS	0/302 (0%)		2/302 (0.7%)
Colitis NOS	0/302 (0%)		2/302 (0.7%)
Colonic hemorrhage	0/302 (0%)		1/302 (0.3%)
Colonic perforation	0/302 (0%)		1/302 (0.3%)
Diarrhea NOS	1/302 (0.3%)		9/302 (3%)
Gastritis NOS	0/302 (0%)		1/302 (0.3%)
Gastrointestinal - Other	0/302 (0%)		1/302 (0.3%)
Ileus paralytic	1/302 (0.3%)		0/302 (0%)
Lower gastrointestinal hemorrhage	0/302 (0%)		1/302 (0.3%)
Nausea	1/302 (0.3%)		3/302 (1%)
Pancreatitis NOS	0/302 (0%)		1/302 (0.3%)
Proctalgia	0/302 (0%)		1/302 (0.3%)
Stomatitis	0/302 (0%)		1/302 (0.3%)
Vomiting NOS	1/302 (0.3%)		1/302 (0.3%)
General disorders
Chest pain	1/302 (0.3%)		0/302 (0%)
Edema: limb	1/302 (0.3%)		0/302 (0%)
Fatigue	0/302 (0%)		4/302 (1.3%)
Multi-organ failure	0/302 (0%)		1/302 (0.3%)
Pyrexia	0/302 (0%)		1/302 (0.3%)
Sudden death	3/302 (1%)		0/302 (0%)
Syndromes - Other	0/302 (0%)		1/302 (0.3%)
Immune system disorders
Hypersensitivity NOS	0/302 (0%)		1/302 (0.3%)
Infections and infestations
Bladder infection NOS	0/302 (0%)		1/302 (0.3%)
Infection - Other	1/302 (0.3%)		0/302 (0%)
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Brain + Spinal cord (encephalomyelitis)	0/302 (0%)		1/302 (0.3%)
Infection with normal ANC or Grade 1 or 2 neutrophils: Blood	0/302 (0%)		1/302 (0.3%)
Infection with unknown ANC: Skin (cellulitis)	0/302 (0%)		1/302 (0.3%)
Kidney infection NOS	1/302 (0.3%)		0/302 (0%)
Lymph gland infection	0/302 (0%)		1/302 (0.3%)
Pneumonia NOS	1/302 (0.3%)		0/302 (0%)
Urinary tract infection NOS	1/302 (0.3%)		1/302 (0.3%)
Injury, poisoning and procedural complications
Dermatitis radiation NOS	1/302 (0.3%)		0/302 (0%)
Fracture NOS	1/302 (0.3%)		1/302 (0.3%)
Vascular access NOS complication	0/302 (0%)		1/302 (0.3%)
Investigations
Blood creatine phosphokinase increased	0/302 (0%)		1/302 (0.3%)
Blood creatinine increased	0/302 (0%)		2/302 (0.7%)
Hypercholesterolemia	1/302 (0.3%)		1/302 (0.3%)
Leukopenia NOS	0/302 (0%)		24/302 (7.9%)
Lymphopenia	0/302 (0%)		4/302 (1.3%)
Metabolic/laboratory - Other	1/302 (0.3%)		1/302 (0.3%)
Neutrophil count	0/302 (0%)		34/302 (11.3%)
Platelet count decreased	1/302 (0.3%)		1/302 (0.3%)
Troponin I increased	0/302 (0%)		2/302 (0.7%)
Weight decreased	0/302 (0%)		2/302 (0.7%)
Metabolism and nutrition disorders
Anorexia	0/302 (0%)		2/302 (0.7%)
Dehydration	1/302 (0.3%)		4/302 (1.3%)
Glucose tolerance impaired	0/302 (0%)		2/302 (0.7%)
Hyperglycemia NOS	0/302 (0%)		4/302 (1.3%)
Hyperkalemia	0/302 (0%)		2/302 (0.7%)
Hypertriglyceridemia	0/302 (0%)		1/302 (0.3%)
Hypokalemia	0/302 (0%)		1/302 (0.3%)
Hyponatremia	0/302 (0%)		1/302 (0.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/302 (0%)		1/302 (0.3%)
Bone pain	0/302 (0%)		2/302 (0.7%)
Chest wall pain	0/302 (0%)		1/302 (0.3%)
Muscle weakness NOS	1/302 (0.3%)		0/302 (0%)
Musculoskeletal/soft tissue - Other	1/302 (0.3%)		0/302 (0%)
Myalgia	0/302 (0%)		1/302 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy - possibly related to cancer treatment	1/302 (0.3%)		1/302 (0.3%)
Nervous system disorders
Cerebral ischemia	1/302 (0.3%)		1/302 (0.3%)
Dizziness	1/302 (0.3%)		1/302 (0.3%)
Neurology - Other	1/302 (0.3%)		0/302 (0%)
Peripheral motor neuropathy	1/302 (0.3%)		1/302 (0.3%)
Peripheral sensory neuropathy	0/302 (0%)		2/302 (0.7%)
Syncope	0/302 (0%)		2/302 (0.7%)
Psychiatric disorders
Depression	0/302 (0%)		1/302 (0.3%)
Euphoric mood	0/302 (0%)		1/302 (0.3%)
Insomnia	0/302 (0%)		1/302 (0.3%)
Libido decreased	0/302 (0%)		1/302 (0.3%)
Renal and urinary disorders
Cystitis NOS	1/302 (0.3%)		2/302 (0.7%)
Pollakiuria	1/302 (0.3%)		3/302 (1%)
Renal failure NOS	1/302 (0.3%)		3/302 (1%)
Urinary incontinence	0/302 (0%)		2/302 (0.7%)
Urinary retention	0/302 (0%)		1/302 (0.3%)
Reproductive system and breast disorders
Ejaculatory disorder NOS	0/302 (0%)		1/302 (0.3%)
Erectile dysfunction NOS	0/302 (0%)		4/302 (1.3%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/302 (0%)		1/302 (0.3%)
Cough	0/302 (0%)		1/302 (0.3%)
Dyspnea	3/302 (1%)		4/302 (1.3%)
Hypoxia	1/302 (0.3%)		0/302 (0%)
Pneumonitis NOS	1/302 (0.3%)		2/302 (0.7%)
Pulmonary/upper respiratory - Other	0/302 (0%)		1/302 (0.3%)
Skin and subcutaneous tissue disorders
Dermatology/skin - Other	1/302 (0.3%)		0/302 (0%)
Localised exfoliation	0/302 (0%)		1/302 (0.3%)
Sweating increased	1/302 (0.3%)		0/302 (0%)
Vascular disorders
Hot flushes NOS	2/302 (0.7%)		2/302 (0.7%)
Hypertension NOS	0/302 (0%)		1/302 (0.3%)
Hypotension NOS	1/302 (0.3%)		2/302 (0.7%)
Peripheral ischemia	1/302 (0.3%)		0/302 (0%)
Thrombosis	0/302 (0%)		2/302 (0.7%)
Other (Not Including Serious) Adverse Events
	Androgen Suppression + Radiation Therapy		Androgen Suppression + Radiation Therapy + Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	278/302 (92.1%)		289/302 (95.7%)
Blood and lymphatic system disorders
Blood/bone marrow - Other	3/302 (1%)		18/302 (6%)
Hemoglobin	37/302 (12.3%)		176/302 (58.3%)
Eye disorders
Lacrimation increased	2/302 (0.7%)		16/302 (5.3%)
Gastrointestinal disorders
Abdominal pain NOS	15/302 (5%)		23/302 (7.6%)
Constipation	29/302 (9.6%)		54/302 (17.9%)
Diarrhea NOS	153/302 (50.7%)		159/302 (52.6%)
Dyspepsia	6/302 (2%)		25/302 (8.3%)
Fecal incontinence	16/302 (5.3%)		13/302 (4.3%)
Gastrointestinal - Other	20/302 (6.6%)		25/302 (8.3%)
Hemorrhoids	15/302 (5%)		13/302 (4.3%)
Nausea	13/302 (4.3%)		81/302 (26.8%)
Proctitis NOS	43/302 (14.2%)		47/302 (15.6%)
Rectal hemorrhage	37/302 (12.3%)		41/302 (13.6%)
Stomatitis	0/302 (0%)		29/302 (9.6%)
Vomiting NOS	8/302 (2.6%)		18/302 (6%)
General disorders
Edema: limb	15/302 (5%)		51/302 (16.9%)
Fatigue	157/302 (52%)		235/302 (77.8%)
Pain - Other	16/302 (5.3%)		26/302 (8.6%)
Investigations
Alanine aminotransferase increased	16/302 (5.3%)		31/302 (10.3%)
Aspartate aminotransferase increased	17/302 (5.6%)		23/302 (7.6%)
Blood alkaline phosphatase increased	7/302 (2.3%)		15/302 (5%)
Leukopenia NOS	20/302 (6.6%)		145/302 (48%)
Lymphopenia	24/302 (7.9%)		63/302 (20.9%)
Metabolic/laboratory - Other	4/302 (1.3%)		25/302 (8.3%)
Neutrophil count	3/302 (1%)		107/302 (35.4%)
Platelet count decreased	11/302 (3.6%)		34/302 (11.3%)
Weight decreased	6/302 (2%)		17/302 (5.6%)
Weight increased	21/302 (7%)		40/302 (13.2%)
Metabolism and nutrition disorders
Anorexia	7/302 (2.3%)		33/302 (10.9%)
Hyperglycemia NOS	16/302 (5.3%)		103/302 (34.1%)
Hypoalbuminemia	5/302 (1.7%)		32/302 (10.6%)
Hypokalemia	2/302 (0.7%)		16/302 (5.3%)
Hyponatremia	3/302 (1%)		28/302 (9.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	25/302 (8.3%)		64/302 (21.2%)
Back pain	25/302 (8.3%)		43/302 (14.2%)
Bone pain	9/302 (3%)		18/302 (6%)
Muscle weakness NOS	16/302 (5.3%)		23/302 (7.6%)
Musculoskeletal/soft tissue - Other	7/302 (2.3%)		17/302 (5.6%)
Myalgia	10/302 (3.3%)		36/302 (11.9%)
Pain in extremity	10/302 (3.3%)		29/302 (9.6%)
Nervous system disorders
Dizziness	8/302 (2.6%)		29/302 (9.6%)
Dysgeusia	2/302 (0.7%)		53/302 (17.5%)
Peripheral motor neuropathy	6/302 (2%)		19/302 (6.3%)
Peripheral sensory neuropathy	20/302 (6.6%)		110/302 (36.4%)
Psychiatric disorders
Anxiety	7/302 (2.3%)		15/302 (5%)
Depression	20/302 (6.6%)		20/302 (6.6%)
Insomnia	22/302 (7.3%)		53/302 (17.5%)
Libido decreased	65/302 (21.5%)		63/302 (20.9%)
Renal and urinary disorders
Bladder pain	6/302 (2%)		18/302 (6%)
Cystitis NOS	33/302 (10.9%)		46/302 (15.2%)
Pollakiuria	209/302 (69.2%)		210/302 (69.5%)
Renal/genitourinary - Other	39/302 (12.9%)		47/302 (15.6%)
Urinary incontinence	34/302 (11.3%)		47/302 (15.6%)
Urinary retention	55/302 (18.2%)		56/302 (18.5%)
Urogenital hemorrhage	10/302 (3.3%)		15/302 (5%)
Reproductive system and breast disorders
Ejaculatory disorder NOS	22/302 (7.3%)		24/302 (7.9%)
Erectile dysfunction NOS	122/302 (40.4%)		120/302 (39.7%)
Gynecomastia	20/302 (6.6%)		25/302 (8.3%)
Respiratory, thoracic and mediastinal disorders
Cough	12/302 (4%)		41/302 (13.6%)
Dyspnea	27/302 (8.9%)		68/302 (22.5%)
Skin and subcutaneous tissue disorders
Alopecia	7/302 (2.3%)		119/302 (39.4%)
Dermatitis exfoliative NOS	7/302 (2.3%)		28/302 (9.3%)
Dermatology/skin - Other	13/302 (4.3%)		24/302 (7.9%)
Dry skin	3/302 (1%)		18/302 (6%)
Nail disorder NOS	1/302 (0.3%)		51/302 (16.9%)
Sweating increased	14/302 (4.6%)		22/302 (7.3%)
Vascular disorders
Hot flushes NOS	206/302 (68.2%)		192/302 (63.6%)
Hypertension NOS	8/302 (2.6%)		15/302 (5%)

Limitations/Caveats

Due to insufficient number of events, local control analysis was not conducted.

More Information

Certain Agreements

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

PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.