A Study of Salvage Radiotherapy With or Without Enzalutamide in Recurrent Prostate Cancer Following Surgery (STEEL)

STEEL: A Randomized Phase II Trial of Salvage Radiotherapy With Standard vs Enhanced Androgen Deprivation Therapy (With Enzalutamide) in Patients With Post-Prostatectomy PSA Recurrences With Aggressive Disease Features

Patients with post-prostatectomy PSA (Prostate Specific Antigen) recurrences with aggressive disease features will receive salvage radiation therapy and standard androgen deprivation therapy (ADT) or enhanced ADT to determine if there is any improvement in progression-free survival when enhanced ADT is used compared to standard ADT.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: Radiation Therapy; Drug: Bicalutamide; Drug: GnRH analog; Drug: Enzalutamide

Detailed Description

PRIMARY OBJECTIVE:

To determine whether, in men with post-prostatectomy PSA (prostate specific antigen) recurrences with aggressive disease features, salvage radiotherapy (SRT) with enhanced androgen deprivation therapy (ADT), consisting of enzalutamide (MDV3100) and a GnRH analog, will improve progression-free survival compared to SRT with standard GnRH analog -based ADT.

• Study Type: Interventional
• Enrollment (Actual): 188
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Sherbrooke, Canada, J1H 5N4
    • CIUSS de l'Estrie - Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
  • Quebec
    • Québec, Quebec, Canada, G1R 2J6
      • CHU de Quebec - L'Hotel-Dieu de Quebec
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85297
      • Arizona Center for Cancer Care - Gilbert
    • Peoria, Arizona, United States, 85381
      • Arizona Center for Cancer Care - Peoria
    • Phoenix, Arizona, United States, 85027
      • Arizona Center for Cancer Care - Phoenix
    • Scottsdale, Arizona, United States, 85251
      • Arizona Center for Cancer Care - Scottsdale East
    • Scottsdale, Arizona, United States, 85258
      • Arizona Center for Cancer Care - Scottsdale North
    • Surprise, Arizona, United States, 85374
      • Arizona Center for Cancer Care - Surprise
  • California
    • Greenbrae, California, United States, 94904
      • Marin Cancer Care, Inc.
    • Greenbrae, California, United States, 94904
      • Marin Health Medical Center
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90033
      • USC Medical Center - Los Angeles County
    • Roseville, California, United States, 95661
      • Sutter Roseville Medical Center
    • Roseville, California, United States, 95661
      • Roseville Radiation Oncology Center
    • Sacramento, California, United States, 95816
      • Sutter Medical Center Sacramento
    • San Francisco, California, United States, 94158
      • University of California, San Francisco
  • Colorado
    • Glenwood Springs, Colorado, United States, 81601
      • Valley View Hospital Cancer Center
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida Health Science Center
    • Orlando, Florida, United States, 32804
      • AdventHealth Orlando
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Savannah, Georgia, United States, 31405
      • Nancy N. & J.C. Lewis Cancer & Research Pavilion
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Overland Park, Kansas, United States, 66210
      • Kansas University Cancer Center Overland Park
    • Westwood, Kansas, United States, 66205
      • Kansas University Cancer Center Westwood
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • East Jefferson General Hospital
    • Metairie, Louisiana, United States, 70006
      • LSU Healthcare Network/Metairie Multi-Specialty Clinic
  • Maine
    • Bath, Maine, United States, 04530
      • Coastal Cancer Treatment Center - Bath
    • Belfast, Maine, United States, 04915
      • Waldo Count General Hospital - Belfast
    • Biddeford, Maine, United States, 04005
      • Maine Health/SMHC Cancer Care and Blood Disorders-Biddeford
    • Norway, Maine, United States, 04268
      • Maine Health/Stephens Memorial - Norway
    • Portland, Maine, United States, 04102
      • Maine Medical Center - Bramhall S Portland
    • Rockport, Maine, United States, 04856
      • Penobscot Bay Medical Center - Rockport
    • Sanford, Maine, United States, 04073
      • Maine Health CC of York County - Sanford
    • Sanford, Maine, United States, 04073
      • Maine Health/SMHCancer Care and Blood Disorders - Sanford
    • Scarborough, Maine, United States, 04074
      • Maine Medical Cancer Center - Scarborough Campus
    • South Portland, Maine, United States, 04106
      • Maine Medical Partners - South Portland
  • Michigan
    • Bloomfield, Michigan, United States, 48302
      • McLaren Cancer Institute - Bloomfield
    • Clarkston, Michigan, United States, 48346
      • 21st Century Oncology MHP - Clarkston
    • Clarkston, Michigan, United States, 48346
      • McLaren Cancer Institute - Clarkston
    • Dearborn, Michigan, United States, 48124
      • William Beaumont Hospital - Dearborn
    • Detroit, Michigan, United States, 48201
      • Wayne State/Karmanos Cancer Institute
    • Farmington Hills, Michigan, United States, 48334
      • 21st Century Oncology MHP - Farmington
    • Flint, Michigan, United States, 48532
      • Singh and Arora Hematology Oncology PC
    • Flint, Michigan, United States, 48532
      • McLaren Cancer Institute - Flint
    • Lansing, Michigan, United States, 48910
      • McLaren Cancer Institute - Greater Lansing
    • Lansing, Michigan, United States, 48912
      • Mid-Michigan Physicians - Lansing
    • Lapeer, Michigan, United States, 48446
      • McLaren Cancer Institute - Lapeer Region
    • Macomb, Michigan, United States, 48044
      • 21st Century Oncology MHP - Macomb
    • Madison Heights, Michigan, United States, 48071
      • 21st Century Oncology MHP - Madison Heights
    • Mount Clemens, Michigan, United States, 48043
      • McLaren Cancer Institute - Macomb
    • Mount Pleasant, Michigan, United States, 48858
      • McLaren Cancer Institute - Central Michigan
    • Owosso, Michigan, United States, 48867
      • McLaren Cancer Institute - Owosso
    • Petoskey, Michigan, United States, 49770
      • McLaren Cancer Institute - Northern Michigan
    • Port Huron, Michigan, United States, 48060
      • McLaren Cancer Institute - Port Huron
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital - Royal Oak
    • Sterling Heights, Michigan, United States, 48314
      • William Beaumont Hospital - Troy
    • Troy, Michigan, United States, 48098
      • 21st Century Oncology MHP - Troy
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA - Maplewood
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center
    • Saint Louis Park, Minnesota, United States, 55416
      • HealthPartners, Inc.
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64154
      • Kansas University Cancer Center North
    • Lee's Summit, Missouri, United States, 64064
      • Kansas University Cancer Center Lee's Summit
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Hampshire
    • Exeter, New Hampshire, United States, 03833
      • Exeter Hospital
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center/Norris Cotton Cancer Center
  • New York
    • Oneida, New York, United States, 13421
      • Upstate Cancer Center Radiation Oncology at Oneida
    • Oneida, New York, United States, 13421
      • University Physicians at Oneida
    • Oswego, New York, United States, 13126
      • University Physicians at Oswego
    • Oswego, New York, United States, 13126
      • Upstate Cancer Radiation Oncology at Oswego
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
    • Syracuse, New York, United States, 13210
      • Upstate Cancer Center at Hill Radiation Oncology
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • UNC REX Cancer Center
    • Raleigh, North Carolina, United States, 27614
      • Rex Cancer Center of Wakefield
  • Pennsylvania
    • Ephrata, Pennsylvania, United States, 17522
      • WellSpan Health - Ephrata Cancer Center
    • Gettysburg, Pennsylvania, United States, 17325
      • WellSpan Health - Adams Cancer Center
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Lebanon, Pennsylvania, United States, 17402
      • WellSpan Health - Sechler Family Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center - Shadyside Hospital
    • York, Pennsylvania, United States, 17403
      • WellSpan Health - York Hospital
  • South Carolina
    • Greer, South Carolina, United States, 29650
      • Gibbs Cancer Center - Pelham
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center - Dallas
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital
    • Cedar City, Utah, United States, 84721
      • Cedar City Hospital
    • Logan, Utah, United States, 84341
      • Logan Regional Medical Center
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center
    • St. George, Utah, United States, 84790
      • Dixie Regional Medical Center
  • Vermont
    • Saint Johnsbury, Vermont, United States, 05819
      • Dartmouth Hitchcock Medical Center/Norris Cancer Ctr. - St. Johnsbury
  • Virginia
    • Hampton, Virginia, United States, 23666
      • Sentara Cancer Institute at Sentara CarePlex Hospital
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Hospital
    • Virginia Beach, Virginia, United States, 23454
      • Sentara Virginia Beach General Hospital
  • Wisconsin
    • Antigo, Wisconsin, United States, 54409
      • Aspirus Langlade Hospital
    • Johnson Creek, Wisconsin, United States, 53038
      • University Cancer Center Johnson Creek
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Menomonee Falls, Wisconsin, United States, 53051
      • Froedtert Menomonee Falls Hospital
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital & the Medical College of Wisconsin
    • Oak Creek, Wisconsin, United States, 53154
      • Drexel Town Square
    • Wausau, Wisconsin, United States, 54401
      • Aspirus Regional Cancer Center
    • West Bend, Wisconsin, United States, 53095
      • Froedtert West Bend Hospital
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Aspirus Cancer Care - Wisconsin Rapids

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pathologically (histologically) proven adenocarcinoma confirmed by prostatectomy performed within 10 years prior to registration and any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted.
• Prostate-specific antigen (PSA) level (≥ 0.2 ng/mL) within 120 days prior to registration. Patients must have a PSA ≥ 0.2 ng/mL prior to starting ADT. For patients being followed by an ultrasensitive PSA assay, a serum PSA concentration of ≥ 0.10 ng/mL will be considered eligible.
• GnRH analog may be started no more than 42 days prior study entry.
• Hemoglobin ≥ 9.0 g/dL, independent of transfusion and/or growth factors within 90 days prior to registration.
• Platelet count ≥ 75,000 x 10^9/µL independent of transfusion and/or growth factors within 90 days prior to registration.

• At least 1 of the following aggressive features:

  • Gleason score of 8-10 (note any Gleason score is eligible)

  • Seminal vesicle invasion (SVI) (note any pT stage American Joint Committee on Cancer (AJCC) v8.0 is eligible but a pT stage

    ≥ pT3b is considered aggressive)

  • Locoregional node involvement at radical prostatectomy (RP) (pN1)
  • Persistently elevated PSA post-RP nadir (PEPP) defined as PSA > 0.1 ng/mL after radical prostatectomy
  • PSA ≥ 0.7 ng/mL
• Serum albumin ≥ 3.0 g/dL within 90 days prior to registration
• Glomerular filtration rate (GFR) ≥35 mL/min estimated by Cockcroft-Gault or measured directly by 24 hour urine creatinine within 90 days prior to registration.
• Serum total bilirubin ≤1.5 × upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject is eligible) within 90 days prior to registration.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 × ULN within 90 days prior to registration.
• History and physical with Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 or within 90 days prior to registration.

Exclusion Criteria:

• Definitive clinical or radiologic evidence of metastatic disease with the exception of locoregional lymph nodes.
• Prior invasive malignancy (except non-melanomatous skin cancer carcinoma in situ of the male breast, penis, oral cavity, or stage Ta of the bladder, or stage I completely resected melanoma) unless disease free for a minimum of 2 years).
• Prior systemic chemotherapy for the study cancer. Note: prior chemotherapy for a different cancer is allowable.
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.

• History of any of the following:

  • Documented inflammatory bowel disease
  • Transmural myocardial infarction within the last 4 months prior to registration.
  • New York Heart Association Functional Classification III/IV within 4 months prior to registration.
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 4 months prior to registration
  • History of loss of consciousness or transient ischemic attack within 12 months prior to randomization
  • History of seizure disorder or condition that may predispose to seizure (e.g. prior cortical stroke or significant brain trauma)
  • History of uncontrolled hypertension defined as a sustained systolic blood pressure in excess of 150 mmHg or a sustained diastolic blood pressure in excess of 90 mmHg despite optimized antihypertensive therapy.
  • History of repeated falls and fractures over the past 12 months that in the opinion of the treating investigator would put the patient at risk for poor bone outcomes from androgen receptor targeted therapy
• Known gastrointestinal disorder affecting absorption of oral medications.
• Active uncontrolled infection defined as an identified infectious condition that requires active therapy that has not yet been completed.
• HIV positive patients with CD4 count < 200 cells/microliter within 30 days prior to registration OR HIV patients under treatment with highly active antiretroviral therapy (HAART) within 30 days prior to registration regardless of CD4 count. Note: HIV testing is not required for eligibility for this protocol as it is self-reported. This exclusion criterion is necessary because the treatments involved in this protocol may be immunosuppressive and/or interact with HAART.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Salvage Radiation Therapy (SRT) + Standard androgen deprivation therapy (ADT); Standard ADT: 24 months of GnRH analog (any formulation) with optional 1-4 months of bicalutamide (50 mg/day). SRT: Starting within 0-70 days of initiation of GnRH analog, 66.6-70.2 Gy as 1.8 Gy/fraction in 37-39 fractions or 66.0-70.0 Gy as 2.0 Gy/fraction in 33-35 fractions lasting approximately 7-8 weeks, and optional lymph node boost.	Radiation: Radiation Therapy; daily fractions; Other Names: Radiotherapy; RT; Image-Guided Radiation Therapy (IGRT); Drug: Bicalutamide; tablet; Other Names: Casodex®; Drug: GnRH analog; Injection; Other Names: Zoladex®; leuprolide acetate; goserelin acetate; Trelstar®; Gonadotropin-releasing hormone analog; Lupron®; Eligard™; Viadur™
Experimental: Salvage Radiation Therapy + Enhanced ADT; Enhanced ADT: 24 months of GnRH analog (any formulation) with 24 months of enzalutamide (160 mg/day). SRT: Starting within 0-70 days of initiation of GnRH analog, 66.6-70.2 Gy as 1.8 Gy/fraction in 37-39 fractions or 66.0-70.0 Gy as 2.0 Gy/fraction in 33-35 fractions lasting approximately 7-8 weeks, and optional lymph node boost.	Radiation: Radiation Therapy; daily fractions; Other Names: Radiotherapy; RT; Image-Guided Radiation Therapy (IGRT); Drug: GnRH analog; Injection; Other Names: Zoladex®; leuprolide acetate; goserelin acetate; Trelstar®; Gonadotropin-releasing hormone analog; Lupron®; Eligard™; Viadur™; Drug: Enzalutamide; tablet; Other Names: Xtandi®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Alive Without Progression (Progression-Free Survival)	Progression-free survival (PFS) is estimated by the Kaplan-Meier method. PFS time is measured from randomization to the date of first PFS failure (biochemical or clinical failure, initiation of new unplanned anticancer treatment, or death from any cause) or last known follow-up (censored). Analysis was to occur after progression or death was reported for 101 participants. Biochemical failure is defined as first post-RT detectable PSA (PSA ≥ 0.05). Clinical failure is defined as either a local, regional, or distant failure.	From randomization to first failure or last known follow-up. Median follow-up time at the time of analysis was 33.1 months. The 1- and 2-year estimates are reported.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to End of RT in the 5-level European Quality of Life Questionnaire (EQ-5D-5L) Index Score	The EQ-5D-5L is a self-assessment questionnaire. The index score is computed from 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). Change score was calculated by subtracting baseline from later score, with a positive change score indicating improvement.	Baseline and end of radiation treatment (RT). End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.
Change From Baseline to One Year After End of RT in the EQ-5D-5L Index Score	The EQ-5D-5L is a self-assessment questionnaire. The index score is computed from 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). Change score was calculated by subtracting baseline from later score, with a positive change score indicating improvement.	Baseline and one year after end RT. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.
Change From Baseline to Two Years After End of RT in the EQ-5D-5L Index Score	The EQ-5D-5L is a self-assessment questionnaire. The index score is computed from 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 5 problem levels (1-none to 5-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). Change score was calculated by subtracting baseline from later score, with a positive change score indicating improvement.	Baseline and two years after end of RT. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.
Change From Baseline to End of RT in the 7-item Patient Reported Outcomes Measurement Information System - Fatigue Short Form (PROMIS-F SF 7a) [PROMIS Fatigue Score]	The PROMIS fatigue score measures self-reported fatigue symptoms over the past 7 days. Possible raw scores range from 29.4 to 83.2 (higher raw score indicating greater fatigue) and are converted into standardized T-scores (mean=50, standard deviation=10) with higher scores also indicating greater fatigue. Change score is calculated by subtracting baseline T-score from later T-score, with a positive change score indicating increased fatigue.	Baseline and end of RT. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.
Change From Baseline to One Year After the End of RT in the 7-item Patient Reported Outcomes Measurement Information System - Fatigue Short Form (PROMIS-F SF 7a) [PROMIS Fatigue Score]	The PROMIS fatigue score measures self-reported fatigue symptoms over the past 7 days. Possible raw scores range from 29.4 to 83.2 (higher raw score indicating greater fatigue) and are converted into standardized T-scores (mean=50, standard deviation=10) with higher scores also indicating greater fatigue. Change score is calculated by subtracting baseline T-score from later T-score, with a positive change score indicating increased fatigue.	Baseline and one year after end of RT. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.
Change From Baseline to Two Years After the End of RT in the 7-item Patient Reported Outcomes Measurement Information System - Fatigue Short Form (PROMIS-F SF 7a) [PROMIS Fatigue Score]	The PROMIS fatigue score measures self-reported fatigue symptoms over the past 7 days. Possible raw scores range from 29.4 to 83.2 (higher raw score indicating greater fatigue) and are converted into standardized T-scores (mean=50, standard deviation=10) with higher scores also indicating greater fatigue. Change score is calculated by subtracting baseline T-score from later T-score, with a positive change score indicating increased fatigue.	Baseline, two years after end of RT. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.
Number of Participants Any Adverse Event Occuring Within 30 Days Following the End of Treatment	Common Terminology Criteria for Adverse Events (version 5) grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.	From randomization to 30 days after the end of RT. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.
Number of Participants With Post-baseline Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Scores ≥ 3	PRO-CTCAE is a patient-reported outcome (PRO) measurement system developed to evaluate symptomatic toxicity in patients on cancer clinical trials, asking the patient about experience over the last seven days. Scores may reflect worst severity of the symptom (0=None, 1=Mild, 2=Moderate, 3=Severe, and 4=Very severe), frequency of the symptom (0=Never, 1=Rarely, 2=Occasionally, 3=Frequently, 4=Almost constantly), or the symptom's interference with one's "usual or daily activities" (0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much). The symptom row title will indicate "Severity", "Frequency", or "Interference". All scores are compared between arms; statistical analysis results are entered for p-values < 0.05.	End of RT, one and two years after the end of RT. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.
Percentage of Participants With Biochemical Failure	Biochemical failure is defined as the first detectable post-RT prostate-specific antigen (PSA) value (≥ 0.05) or the initiation of salvage hormone therapy. Failure rates are estimated using the cumulative incidence method, treating death as a competing risk, and otherwise censoring participants alive at time of analysis.	From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months. The 1- and 2-year estimates are reported.
Percentage of Participants With Alternative Biochemical Failure	Alternative biochemical failure is defined as first post-RT PSA ≥ 0.1 ng/mL or initiation of salvage hormone therapy. Failure rates are estimated using the cumulative incidence method, treating death as a competing risk, and otherwise censoring participants alive at time of analysis.	From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months. The 1- and 2-year estimates are reported.
Percentage of Participants With Hormone-refractory Disease	Hormone-refractory disease is defined as three rises in PSA during salvage androgen deprivation, with the date determined as the midway date between the last non-rising PSA and the first of the three rises. Failure rates were to be estimated using the cumulative incidence method, treating death as a competing risk, and otherwise censoring participants alive at time of analysis, but for endpoints with < 10 events overall, such as this one, only the counts of participants with the event are provided.	From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months.
Percentage of Participants With Distant Metastasis	Distant failure is defined as first radiographic evidence of distant metastasis (e.g., bone scan, computed tomography (CT), magnetic resonance imaging (MRI)). Failure rates were to be estimated using the cumulative incidence method, treating death as a competing risk, and otherwise censoring participants alive at time of analysis, but for endpoints with < 10 events overall, such as this one, only the counts of participants with the event are provided.	From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months.
Percentage of Participants With Prostate Cancer Death	Cause-specific mortality is defined as death due to prostate cancer. Failure rates were to be estimated using the cumulative incidence method, treating death as a competing risk, and otherwise censoring participants alive at time of analysis, but for endpoints with < 10 events overall, such as this one, only the counts of participants with the event are provided.	From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months.
Percentage of Participants Alive (Overall Survival)	Survival rates were to be estimated using the Kaplan-Meier method, censoring participants alive at time of analysis, but for endpoints with < 10 events overall, such as this one, only counts are provided. In this case, the number of participants without event (death), which is the number of participants alive.	From randomization to death or last known follow-up, whichever occurs first. Median follow-up time at the time of analysis was 33.1 months.
Number of Participants by Highest Grade Adverse Event Reported CTCAE v5	Common Terminology Criteria for Adverse Events (version 5) grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.	From randomization to death or last known follow-up. Median follow-up time at the time of analysis was 33.1 months.
Number of Participants With Any Grade 3+ Adverse Event Occuring After 30 Days Following the End of RT	Common Terminology Criteria for Adverse Events (version 5) grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.	From 31 days after the end of RT to death or last known follow-up. Median follow-up was 33.1 months. End of RT can vary greatly depending on when it starts, which can be from 0 to 70 days from the start of ADT, and lasting 7-8 weeks.

Collaborators and Investigators

• Sponsor: RTOG Foundation, Inc.
• Collaborators: Pfizer; Astellas Pharma Inc
• Investigators: Principal Investigator: Edwin Posadas, MD, RTOG Foundation; Principal Investigator: Hiram Gay, MD, RTOG Foundation

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2019
• Primary Completion (Actual): April 7, 2023
• Study Completion (Estimated): September 15, 2029

Study Registration Dates

• First Submitted: January 16, 2019
• First Submitted That Met QC Criteria: January 16, 2019
• First Posted (Actual): January 18, 2019

Study Record Updates

• Last Update Posted (Estimated): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Enzalutamide; Post-prostatectomy; STEEL
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Therapeutics; Leuprolide; Goserelin; Triptorelin Pamoate; Gonadotropin-Releasing Hormone; luprolide acetate gel depot; Radiotherapy; enzalutamide; Radiotherapy, Image-Guided; bicalutamide
• Other Study ID Numbers: RTOG 3506; STEEL (Other Identifier: RTOG Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No