Radiation Therapy in Treating Patients With Stage II Prostate Cancer

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00033631
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 1,532
• Locations: 86
• Arms: 2
• Patients Per Site: 17.8

Study Details

Study Description

Brief Summary

RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. It is not yet known which dose of radiation therapy is more effective in treating stage II prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of two different doses of specialized radiation therapy in treating patients who have stage II prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Radiation: 70.2 Gy 3D-CRT/IMRT; Radiation: 79.2 Gy 3D-CRT/IMRT	Phase 3

Detailed Description

OBJECTIVES:

• Compare the overall survival of patients with stage II adenocarcinoma of the prostate treated with high- vs standard-dose three-dimensional conformal or intensity-modulated radiotherapy.

• Compare the freedom from prostate-specific antigen failure, disease-specific survival, local progression, and distant metastases in patients treated with these regimens.

• Compare the probability of tumor control and normal tissue complications in patients treated with these regimens.

• Compare the incidence of grade 2 or greater genitourinary and gastrointestinal acute and late toxicity in patients treated with these regimens.

• Compare the quality of life, including sexual function, of patients treated with these regimens.

• Correlate histopathologic or tumor-specific cytogenetic or chromosomal markers with cancer control outcomes in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to Gleason score and prostate-specific antigen (PSA) level (Gleason score 2-6, PSA ≥10 mg/mL but < 20 ng/mL vs Gleason score 7, PSA < 15 ng/mL) and radiation modality (three-dimensional conformal radiotherapy [3D-CRT] vs intensity-modulated radiotherapy [IMRT]). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo standard-dose 3D-CRT or IMRT once daily, 5 days a week, for 7.8 weeks (39 treatment days).

• Arm II: Patients undergo high-dose 3D-CRT or IMRT once daily, 5 days a week, for 8.8 weeks (44 treatment days).

Quality of life (QOL) is assessed initially at baseline. After completion of radiotherapy, QOL is assessed every 3 months for 1 year and then every 6 months for 4 years.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,520 patients (760 per treatment arm) will be accrued for this study within 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1532 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized Study Of High Dose 3D-CRT/IMRT Versus Standard Dose 3D-CRT/IMRT In Patients Treated For Localized Prostate Cancer
• Study Start Date: Mar 1, 2002
• Actual Primary Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 70.2 Gy 70.2 Gy 3D-CRT/IMRT	Radiation: 70.2 Gy 3D-CRT/IMRT; Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 39 Fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 70.2 Gy.; Other Names: 3D conformal radiation therapy intensity modulated radiation therapy
Experimental: 79.2 Gy 79.2 Gy 3D-CRT/IMRT	Radiation: 79.2 Gy 3D-CRT/IMRT; Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 79.2 Gy in 44 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 79.2 Gy.; Other Names: 3D conformal radiation therapy intensity modulated radiation therapy

Outcome Measures

Primary Outcome Measures

1. Overall Survival [From randomization to date of failure (death) or last follow-up. Analysis occurs after all patients have been potentially followed for 8 years.]

   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 know to be alive are censored at date of last contact.

Secondary Outcome Measures

1. Prostate-specific Antigen (PSA) Failure by American Society for Therapeutic Radiology and Oncology (ASTRO) Definition [From randomization to date of failure (3 consecutive rises) or death or last follow-up. Analysis occurred after patients have been potentially followed for 5 years.]

   Failure is defined as having 3 consecutive elevations of post-treatment PSA or starting hormones after one or more elevations in post-treatment PSA but before three consecutive elevations were documented. The failure day date was the midpoint between last non-rising PSA and first PSA rise. Failure rates are estimated by the cumulative incidence method. Patients last known to be alive are censored at date of last contact.

2. Disease Specific Survival [From randomization to date of failure (death due to prostate cancer) or death from other cause or last follow-up. Analysis occurs at the same time as the primary endpoint.]

   Survival time is defined as time from randomization to the date of death due to prostate cancer and is estimated by the cumulative incidence method. Patients last know to be alive are censored at date of last contact. Death due to prostate cancer was defined as primary cause of death certified as due to prostate cancer, or death in association with any of the following conditions: Further clinical tumor progression occurring after initiation of salvage anti-tumor therapy, a rise (that exceeds 1.0 ng/ml) in the serum PSA level on at least two consecutive occasions that occurred during or after salvage androgen suppression therapy, or disease progression in the absence of any anti-tumor therapy.

3. Local Progression [From randomization to date of failure (local progression) or death or last follow-up. Analysis occurs at the same time as the primary endpoint.]

   Failure time is defined as time from randomization to the date of progression (increase in palpable abnormality), failure of regression of the palpable tumor by two years, and redevelopment of a palpable abnormality after complete disappearance of previous abnormalities. Failure rates are estimated by the cumulative incidence method. Patients last know to be alive are censored at date of last contact.

4. Distant Metastases [From randomization to date of failure (distant metastasis) or death or last follow-up. Analysis occurs at the same time as the primary endpoint.]

   Failure time is defined as time from randomization to the date of documented regional nodal recurrence or development of distant disease. Failure rates are estimated by the cumulative incidence method. Patients last know to be alive are censored at date of last contact.

5. Grade 2 or Greater Genitourinary or Gastrointestinal Toxicity [From the start of treatment to 90 days. Analysis occurs at the same time as the primary endpoint]

   Rate of acute 2+ grade genitourinary(GU)/gastrointestinal(GI) toxicity graded by Common Toxicity Criteria (CTC) version 2.0

6. Percentage of Participants With Erectile Disfuction at 12 Months [Twelve months from randomization]

   The International Index of Erectile Function Questionnaire (IIEF) is the primary measure for erectile function (ED). IIEF question number 1 ("How often were you able to get an erection during sexual activity?") is scored from: none/almost never (response 0-1) or < half the time (response 2-3) to most times/almost always/always (response 4-5). A response of 0 to 3 on question number 1 of the IIEF is considered erectile dysfunction.

7. Number of Participants With Improved, Stable, and Declined Spitzer Quality of Life Index (SQLI) at 12 Months [Baseline and 12 months from randomization]

   The SQLI measures quality of life for patients with cancer and other chronic diseases. Possible scores range from 0 to 10, with higher scores indicating a better outcome. Change from Baseline is defined as 12 month SQLI - baseline SQLI and is classified as follows: Improvement: when change >= to the standard error of measurement with reliability quotient of 0.5 (SEM); Stable: when -SEM < change < SEM; Declined: when change <= SEM.

8. Quality Adjusted Survival by SQLI [From randomization to 5 years.]

9. Tumor Control Probability [From randomization to date of failure (tumor progression) or last follow-up. Analysis can occur any time after the primary endpoint analysis.]

10. Normal Tissue Complication Probability [From randomization to last follow-up. Analysis can occur any time after the primary endpoint analysis.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

• Clinical stage T1b-T2b

• Meets one of the following criteria:

• Gleason score 2-6 AND prostate-specific antigen (PSA) ≥ 10 ng/mL but < 20 ng/mL

• Gleason score 7 AND PSA < 15 ng/mL

• No regional lymph node involvement

• No distant metastases

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• Zubrod 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• No other invasive malignancy within the past 5 years except localized basal cell or squamous cell skin cancer

• No other major medical or psychiatric illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior cytotoxic chemotherapy

• No concurrent cytotoxic chemotherapy

Endocrine therapy:

• At least 3 months since prior finasteride

• No other prior hormonal therapy, including:

• Luteinizing hormone-releasing hormone agonists (e.g., goserelin or leuprolide)

• Antiandrogens (e.g., flutamide or bicalutamide)

• Estrogens (e.g., diethylstilbestrol)

• No concurrent (neoadjuvant or adjuvant) hormonal therapy

Radiotherapy:

• No prior pelvic irradiation or brachytherapy

Surgery:

• No prior radical surgery (prostatectomy) or cryosurgery for prostate cancer

• No prior surgical castration (bilateral orchiectomy)

Other:

• At least 3 months since prior finasteride or phytoestrogen preparation (PC-SPES)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Veterans Affairs Medical Center - Long Beach	Long Beach	California	United States	90822
2	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California	United States	95815
3	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
4	Washington Cancer Institute at Washington Hospital Center	Washington	District of Columbia	United States	20010
5	Bay Medical	Panama City	Florida	United States	32401
6	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
7	Oncology Center at Saint Margaret Mercy Healthcare Center	Hammond	Indiana	United States	46320
8	Cancer Center at Ball Memorial Hospital	Muncie	Indiana	United States	47303-3499
9	Providence Medical Center	Kansas City	Kansas	United States	66112
10	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
11	Menorah Medical Center	Overland Park	Kansas	United States	66209
12	Johnson County Radiation Therapy	Overland Park	Kansas	United States	66210
13	Shawnee Mission Medical Center	Shawnee Mission	Kansas	United States	66204
14	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky	United States	40536-0093
15	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
16	Central Maryland Oncology Center	Columbia	Maryland	United States	21044
17	Veterans Affairs Medical Center - Ann Arbor	Ann Arbor	Michigan	United States	48105
18	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
19	Foote Memorial Hospital	Jackson	Michigan	United States	49201
20	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
21	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan	United States	48910
22	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
23	CentraCare Clinic - River Campus	Saint Cloud	Minnesota	United States	56303
24	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi	United States	39581
25	Independence Regional Health Center	Independence	Missouri	United States	64050
26	Truman Medical Center - Hospital Hill	Kansas City	Missouri	United States	64108
27	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri	United States	64111
28	Kansas City Cancer Center at St. Joseph's Medical Mall	Kansas City	Missouri	United States	64114
29	St. Joseph Medical Center	Kansas City	Missouri	United States	64114
30	North Kansas City Hospital	Kansas City	Missouri	United States	64116
31	Parvin Radiation Oncology	Kansas City	Missouri	United States	64116
32	CCOP - Kansas City	Kansas City	Missouri	United States	64131
33	Radiation Oncology Associates of Kansas City at Northland Radiation Oncology Center	Kansas City	Missouri	United States	64154
34	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
35	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri	United States	63110
36	Saint Mary's Regional Medical Center	Reno	Nevada	United States	89503
37	Cancer Institute of New Jersey at Cooper University Hospital - Camden	Camden	New Jersey	United States	08103
38	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
39	Lovelace Medical Center - Downtown	Albuquerque	New Mexico	United States	87102
40	Veterans Affairs Medical Center - Brooklyn	Brooklyn	New York	United States	11209
41	New York Methodist Hospital	Brooklyn	New York	United States	11215
42	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
43	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
44	Cancer Centers of North Carolina - Raleigh	Raleigh	North Carolina	United States	27607
45	Rex Cancer Center at Rex Hospital	Raleigh	North Carolina	United States	27607
46	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
47	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267
48	Precision Radiotherapy at University Pointe	West Chester	Ohio	United States	45069
49	Cancer Treatment Center	Wooster	Ohio	United States	44691
50	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
51	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301-1792
52	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
53	MNAP Oncologic Center	Philadelphia	Pennsylvania	United States	19115
54	Albert Einstein Cancer Center	Philadelphia	Pennsylvania	United States	19141
55	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania	United States	19612-6052
56	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
57	CCOP - Main Line Health	Wynnewood	Pennsylvania	United States	19096
58	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania	United States	19096
59	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
60	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390
61	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234-6200
62	Wilford Hall Medical Center	Lackland Air Force Base	Texas	United States	78236
63	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah	United States	84157
64	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah	United States	84403
65	Dixie Regional Medical Center - East Campus	Saint George	Utah	United States	84770
66	LDS Hospital	Salt Lake City	Utah	United States	84143
67	Danville Regional Medical Center	Danville	Virginia	United States	24541
68	Naval Medical Center - Portsmouth	Portsmouth	Virginia	United States	23708-2197
69	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
70	Community Memorial Hospital Cancer Care Center	Menomonee Falls	Wisconsin	United States	53051
71	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
72	All Saints Cancer Center at Wheaton Franciscan Healthcare	Racine	Wisconsin	United States	53405
73	Tom Baker Cancer Centre - Calgary	Calgary	Alberta	Canada	T2N 4N2
74	Cross Cancer Institute at University of Alberta	Edmonton	Alberta	Canada	T6G 1Z2
75	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
76	Saint John Regional Hospital	Saint John	New Brunswick	Canada	E2L 4L2
77	Doctor H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador	Canada	A1B 3V6
78	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
79	London Regional Cancer Program at London Health Sciences Centre	London	Ontario	Canada	N6A 4L6
80	Northeastern Ontario Regional Cancer Centre	Sudbury	Ontario	Canada	P3E 5J1
81	Cancer Care Program at Thunder Bay Regional Health Sciences	Thunder Bay	Ontario	Canada	P7B 6V4
82	Edmond Odette Cancer Centre at Sunnybrook	Toronto	Ontario	Canada	M4N 3M5
83	Hopital Notre-Dame du CHUM	Montreal	Quebec	Canada	H2L 4M1
84	McGill Cancer Centre at McGill University	Montreal	Quebec	Canada	H2W 1S6
85	Centre Hospitalier Universitaire de Quebec	Quebec City	Quebec	Canada	G1R 2J6
86	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan	Canada	S7N 4H4

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Jeff M. Michalski, MD, Washington University - Saint Louis
• Study Chair: James Purdy, Ph.D., UC Davis
• Study Chair: Deborah W Bruner, Ph.D., Emory University
• Study Chair: Mahul Amin, M.D., Cedars-Sinai

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Publications

• Cranmer-Sargison G. A treatment planning investigation into the dosimetric effects of systematic prostate patient rotational set-up errors. Med Dosim. 2008 Autumn;33(3):199-205. doi: 10.1016/j.meddos.2007.06.005.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00033631
• Other Study ID Numbers: RTOG-0126; CDR0000069306
• First Posted: Jan 27, 2003
• Last Update Posted: Jul 13, 2022
• Last Verified: Jul 1, 2021

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

Study Results

Participant Flow

Arm/Group Title	70.2 Gy	79.2 Gy
Arm/Group Description	70.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 39 Fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 70.2 Gy.	79.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 79.2 Gy in 44 Fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 79.2 Gy.
Period Title: Overall Study
STARTED	769	763
COMPLETED	751	748
NOT COMPLETED	18	15

Baseline Characteristics

Arm/Group Title	70.2 Gy	79.2 Gy	Total
Arm/Group Description	70.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 39 Fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 70.2 Gy.	79.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 79.2 Gy in 44 Fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 79.2 Gy.	Total of all reporting groups
Overall Participants	751	748	1499
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	751 100%	748 100%	1499 100%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
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 know to be alive are censored at date of last contact.
Time Frame	From randomization to date of failure (death) or last follow-up. Analysis occurs after all patients have been potentially followed for 8 years.

Outcome Measure Data

Analysis Population Description

All eligible patients who did not withdraw consent

Arm/Group Title	70.2 Gy	79.2 Gy
Arm/Group Description	70.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 39 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 70.2 Gy.	79.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 79.2 Gy in 44 fractions . All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 79.2 Gy.
Measure Participants	751	748
Number (95% Confidence Interval) [percentage of participants]	88.5 11.8%	88.1 11.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	70.2 Gy, 79.2 Gy
	Comments	The original target sample size was 1520 patients with a requirement of 715 deaths to test the hypothesis of overall survival (OS) efficacy of the 79.2 Gy arm. The trial was designed to detect a hazard ratio (HR) of 1.30 (standard/high-dose) with 90% statistical power at a one-sided significance level of 0.025.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.98
	Comments	Two-sided test, significance level = 0.05
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = 70.2 Gy arm

2. Secondary Outcome

Title	Prostate-specific Antigen (PSA) Failure by American Society for Therapeutic Radiology and Oncology (ASTRO) Definition
Description	Failure is defined as having 3 consecutive elevations of post-treatment PSA or starting hormones after one or more elevations in post-treatment PSA but before three consecutive elevations were documented. The failure day date was the midpoint between last non-rising PSA and first PSA rise. Failure rates are estimated by the cumulative incidence method. Patients last known to be alive are censored at date of last contact.
Time Frame	From randomization to date of failure (3 consecutive rises) or death or last follow-up. Analysis occurred after patients have been potentially followed for 5 years.

Outcome Measure Data

Analysis Population Description

All eligible patients who did not withdraw consent

Arm/Group Title	70.2 Gy	79.2 Gy
Arm/Group Description	70.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 39 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 70.2 Gy.	79.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 79.2 Gy in 44 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 79.2 Gy.
Measure Participants	751	748
Number (95% Confidence Interval) [percentage of participants]	40.2 5.4%	25.2 3.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	70.2 Gy, 79.2 Gy
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two-sided significance level = 0.05
	Method	Gray's test
	Comments	Reference arm is 70.2 Gy arm
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95%; 0.50 to 0.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Disease Specific Survival
Description	Survival time is defined as time from randomization to the date of death due to prostate cancer and is estimated by the cumulative incidence method. Patients last know to be alive are censored at date of last contact. Death due to prostate cancer was defined as primary cause of death certified as due to prostate cancer, or death in association with any of the following conditions: Further clinical tumor progression occurring after initiation of salvage anti-tumor therapy, a rise (that exceeds 1.0 ng/ml) in the serum PSA level on at least two consecutive occasions that occurred during or after salvage androgen suppression therapy, or disease progression in the absence of any anti-tumor therapy.
Time Frame	From randomization to date of failure (death due to prostate cancer) or death from other cause or last follow-up. Analysis occurs at the same time as the primary endpoint.

Outcome Measure Data

Analysis Population Description

All eligible patients who did not withdraw consent

Arm/Group Title	70.2 Gy	79.2 Gy
Arm/Group Description	70.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 39 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 70.2 Gy.	79.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 79.2 Gy in 44 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 79.2 Gy.
Measure Participants	751	748
Number (95% Confidence Interval) [percentage of participants]	1.4 0.2%	0.8 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	70.2 Gy, 79.2 Gy
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	Gray's test
	Comments	Two-sided significance level = 0.05
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; 0.38 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level is 70.2 Gy arm

4. Secondary Outcome

Title	Local Progression
Description	Failure time is defined as time from randomization to the date of progression (increase in palpable abnormality), failure of regression of the palpable tumor by two years, and redevelopment of a palpable abnormality after complete disappearance of previous abnormalities. Failure rates are estimated by the cumulative incidence method. Patients last know to be alive are censored at date of last contact.
Time Frame	From randomization to date of failure (local progression) or death or last follow-up. Analysis occurs at the same time as the primary endpoint.

Outcome Measure Data

Analysis Population Description

All eligible patients who have not withdrawn consent

Arm/Group Title	70.2 Gy	79.2 Gy
Arm/Group Description	70.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 39 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 70.2 Gy.	79.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 79.2 Gy in 44 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 79.2 Gy.
Measure Participants	751	748
Number (95% Confidence Interval) [percentage of participants]	3.5 0.5%	1.8 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	70.2 Gy, 79.2 Gy
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Gray's test
	Comments	Two-sided significance level = 0.05
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.41
	Confidence Interval	(2-Sided) 95%; 0.25 to 0.66
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = 70.2 Gy arm

5. Secondary Outcome

Title	Distant Metastases
Description	Failure time is defined as time from randomization to the date of documented regional nodal recurrence or development of distant disease. Failure rates are estimated by the cumulative incidence method. Patients last know to be alive are censored at date of last contact.
Time Frame	From randomization to date of failure (distant metastasis) or death or last follow-up. Analysis occurs at the same time as the primary endpoint.

Outcome Measure Data

Analysis Population Description

All eligible patients who have not withdrawn consent

Arm/Group Title	70.2 Gy	79.2 Gy
Arm/Group Description	70.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 39 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 70.2 Gy.	79.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 79.2 Gy in 44 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 79.2 Gy.
Measure Participants	751	748
Number (95% Confidence Interval) [percentage of participants]	3.1 0.4%	2.2 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	70.2 Gy, 79.2 Gy
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.051
	Comments	Two-sided significance level = 0.05
	Method	Gray's test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; 0.42 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level is the 70.2 Gy level

6. Secondary Outcome

Title	Grade 2 or Greater Genitourinary or Gastrointestinal Toxicity
Description	Rate of acute 2+ grade genitourinary(GU)/gastrointestinal(GI) toxicity graded by Common Toxicity Criteria (CTC) version 2.0
Time Frame	From the start of treatment to 90 days. Analysis occurs at the same time as the primary endpoint

Outcome Measure Data

Analysis Population Description

Eligible patients with acute adverse event data who did not withdraw consent.

Arm/Group Title	70.2 Gy	79.2 Gy
Arm/Group Description	70.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 39 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 70.2 Gy.	79.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 79.2 Gy in 44 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 79.2 Gy.
Measure Participants	733	728
Number [percentage of participants]	18.8 2.5%	21.0 2.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	70.2 Gy, 79.2 Gy
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments	Two-sided significance level = 0.05
	Method	Chi-squared
	Comments

7. Secondary Outcome

Title	Percentage of Participants With Erectile Disfuction at 12 Months
Description	The International Index of Erectile Function Questionnaire (IIEF) is the primary measure for erectile function (ED). IIEF question number 1 ("How often were you able to get an erection during sexual activity?") is scored from: none/almost never (response 0-1) or < half the time (response 2-3) to most times/almost always/always (response 4-5). A response of 0 to 3 on question number 1 of the IIEF is considered erectile dysfunction.
Time Frame	Twelve months from randomization

Outcome Measure Data

Analysis Population Description

Eligible patients with a response of 4 or 5 (most times/almost always/always) to IIEF question 1 at baseline

Arm/Group Title	70.2 Gy	79.2 Gy
Arm/Group Description	70.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 39 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 70.2 Gy.	79.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 79.2 Gy in 44 fractions . All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 79.2 Gy.
Measure Participants	134	145
Number (95% Confidence Interval) [percentage of participants]	38.06 5.1%	49.66 6.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	70.2 Gy, 79.2 Gy
	Comments	With an expected percentage of erectile disfunction (ED) at 12 months of 29%, a two-sided significance level of 0.05, and 688 patients per arm provides 90% statistical power to detect a reduction in ED to 19%. This calculation assumes 26% ED at baseline and 80% compliance at 12 months. Only participants with baseline ED are analyzed.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0513
	Comments
	Method	Chi-squared
	Comments	Two-sided significance level = 0.05

8. Secondary Outcome

Title	Number of Participants With Improved, Stable, and Declined Spitzer Quality of Life Index (SQLI) at 12 Months
Description	The SQLI measures quality of life for patients with cancer and other chronic diseases. Possible scores range from 0 to 10, with higher scores indicating a better outcome. Change from Baseline is defined as 12 month SQLI - baseline SQLI and is classified as follows: Improvement: when change >= to the standard error of measurement with reliability quotient of 0.5 (SEM); Stable: when -SEM < change < SEM; Declined: when change <= SEM.
Time Frame	Baseline and 12 months from randomization

Outcome Measure Data

Analysis Population Description

Eligible participants with baseline and 12 month SQLI

Arm/Group Title	70.2 Gy	79.2 Gy
Arm/Group Description	70.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 39 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 70.2 Gy.	79.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 79.2 Gy in 44 fractions . All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 79.2 Gy.
Measure Participants	547	517
Improved	91 12.1%	91 12.2%
Stable	366 48.7%	331 44.3%
Declined	90 12%	95 12.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	70.2 Gy, 79.2 Gy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.59
	Comments
	Method	Chi-squared
	Comments	Two-sided significance level = 0.05

9. Secondary Outcome

Title	Quality Adjusted Survival by SQLI
Time Frame	From randomization to 5 years.

Outcome Measure Data

Analysis Population Description

This analysis will not be done because we are unable to find the required algorithm for converting SQLI scores into utilities, which is needed for quality adjusted survival analysis.

Arm/Group Title	70.2 Gy	79.2 Gy
Arm/Group Description	70.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 39 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 70.2 Gy.	79.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 79.2 Gy in 44 fractions . All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 79.2 Gy.
Measure Participants	0	0

10. Secondary Outcome

Title	Tumor Control Probability
Time Frame	From randomization to date of failure (tumor progression) or last follow-up. Analysis can occur any time after the primary endpoint analysis.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Normal Tissue Complication Probability
Time Frame	From randomization to last follow-up. Analysis can occur any time after the primary endpoint analysis.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Adverse Event Reporting Description	Eligible patients with toxicity data who did not withdraw consent. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Arm/Group Title	70.2 Gy		79.2 Gy
Arm/Group Description	70.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 39 Fractions . All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 70.2 Gy.		79.2 Gy 3D-CRT/IMRT: Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 44 Fractions . All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 79.2 Gy.
All Cause Mortality
	70.2 Gy		79.2 Gy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	70.2 Gy		79.2 Gy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/744 (4%)		43/737 (5.8%)
Cardiac disorders
Left ventricular failure	0/744 (0%)		1/737 (0.1%)
Myocardial ischaemia	2/744 (0.3%)		1/737 (0.1%)
Gastrointestinal disorders
Abdominal pain NOS	1/744 (0.1%)		0/737 (0%)
Diarrhea (with colostomy)	0/744 (0%)		1/737 (0.1%)
Diarrhea NOS	2/744 (0.3%)		0/737 (0%)
Late RT Toxicity: Bowel : NOS	1/744 (0.1%)		1/737 (0.1%)
Late RT Toxicity: Other GI : NOS	1/744 (0.1%)		4/737 (0.5%)
General disorders
Chest pain	1/744 (0.1%)		0/737 (0%)
Injection site reaction NOS	0/744 (0%)		1/737 (0.1%)
Late RT Toxicity: Other : NOS	1/744 (0.1%)		3/737 (0.4%)
Pain due to radiation	0/744 (0%)		2/737 (0.3%)
Pain-other	1/744 (0.1%)		0/737 (0%)
Renal and urinary disorders
Dysuria	0/744 (0%)		2/737 (0.3%)
Late RT Toxicity: Bladder/Other GU: NOS	0/744 (0%)		3/737 (0.4%)
Urinary incontinence	21/744 (2.8%)		21/737 (2.8%)
Urinary retention	1/744 (0.1%)		2/737 (0.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea NOS	0/744 (0%)		1/737 (0.1%)
Skin and subcutaneous tissue disorders
Skin-Other	0/744 (0%)		2/737 (0.3%)
Vascular disorders
Hemorrhage-Other	0/744 (0%)		2/737 (0.3%)
Other (Not Including Serious) Adverse Events
	70.2 Gy		79.2 Gy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	714/744 (96%)		704/737 (95.5%)
Gastrointestinal disorders
Diarrhea NOS	58/744 (7.8%)		50/737 (6.8%)
Late RT Toxicity: Bowel : NOS	90/744 (12.1%)		128/737 (17.4%)
Late RT Toxicity: Other GI : NOS	90/744 (12.1%)		107/737 (14.5%)
Proctitis NOS	33/744 (4.4%)		45/737 (6.1%)
General disorders
Fatigue	51/744 (6.9%)		51/737 (6.9%)
Late RT Toxicity: Other : NOS	68/744 (9.1%)		90/737 (12.2%)
Renal and urinary disorders
Dysuria	52/744 (7%)		53/737 (7.2%)
Late RT Toxicity: Bladder/Other GU: NOS	99/744 (13.3%)		126/737 (17.1%)
Urinary frequency	566/744 (76.1%)		585/737 (79.4%)
Urinary incontinence	234/744 (31.5%)		229/737 (31.1%)
Reproductive system and breast disorders
Impotence	611/744 (82.1%)		599/737 (81.3%)

Limitations/Caveats

The data monitoring committee (DMC) recommended early reporting of the trial when the third interim analysis futility boundary was crossed.

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.