Parallel Phase III Randomized Trials for High Risk Prostate Cancer Evaluating De-Intensification for Lower Genomic Risk and Intensification of Concurrent Therapy for Higher Genomic Risk With Radiation (PREDICT-RT*)
Trial ID: NCT04513717
Status: ACTIVE_NOT_RECRUITING
Study type: INTERVENTIONAL
Phase: PHASE3
Start date: 2021-01-21
Completion date: 2033-12-31
Sponsor: NRG Oncology
Collaborators: National Cancer Institute (NCI)
Conditions: Prostate Adenocarcinoma; Stage III Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8
Interventions: Apalutamide; Bicalutamide; Biospecimen Collection; Bone Scan; Buserelin; Computed Tomography; Degarelix; Flutamide; Goserelin; Histrelin; Leuprolide; Magnetic Resonance Elastography; Positron Emission Tomography; Quality-of-Life Assessment; Questionnaire Administration; Radiation Therapy; Relugolix; Triptorelin
Locations: Fairbanks Memorial Hospital; Banner MD Anderson Cancer Center; Arizona Center for Cancer Care - Gilbert; Arizona Center for Cancer Care-Peoria; Arizona Center for Cancer Care - Phoenix; Arizona Center for Cancer Care - Scottsdale; University of Arizona Cancer Center-North Campus; University of Arkansas for Medical Sciences; Sutter Cancer Centers Radiation Oncology Services-Auburn; AIS Cancer Center at San Joaquin Community Hospital; Alta Bates Summit Medical Center-Herrick Campus; Sutter Cancer Centers Radiation Oncology Services-Cameron Park; Enloe Medical Center; City of Hope Corona; City of Hope Comprehensive Cancer Center; Kaiser Permanente Dublin; UC San Diego Health System - Encinitas; Kaiser Permanente-Fremont; Palo Alto Medical Foundation-Fremont; Washington Hospital; Kaiser Permanente-Fresno; Marin General Hospital; UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care; City of Hope at Irvine Lennar; UC San Diego Moores Cancer Center; City of Hope Antelope Valley; Los Angeles General Medical Center; USC / Norris Comprehensive Cancer Center; Cedars Sinai Medical Center; Fremont - Rideout Cancer Center; Memorial Medical Center; Kaiser Permanente-Modesto; Providence Queen of The Valley; Kaiser Permanente-Oakland; Saint Joseph Hospital - Orange; UC Irvine Health/Chao Family Comprehensive Cancer Center; Palo Alto Medical Foundation Health Care; Stanford Cancer Institute Palo Alto; Kaiser Permanente-Roseville; Sutter Cancer Centers Radiation Oncology Services-Roseville; Kaiser Permanente Downtown Commons; Sutter Medical Center Sacramento; University of California Davis Comprehensive Cancer Center; Kaiser Permanente-South Sacramento; California Protons Cancer Therapy Center; Sharp Memorial Hospital; Kaiser Permanente-San Francisco; UCSF Medical Center-Mission Bay; Kaiser Permanente-Santa Teresa-San Jose; Stanford Cancer Center South Bay; Kaiser Permanente San Leandro; UCSF Cancer Center - San Mateo; Ridley-Tree Cancer Center; Kaiser Permanente Medical Center - Santa Clara; Kaiser Permanente-Santa Rosa; City of Hope South Pasadena; Kaiser Permanente-South San Francisco; Palo Alto Medical Foundation-Sunnyvale; Cedars-Sinai Cancer - Tarzana; City of Hope South Bay; Torrance Memorial Physician Network - Cancer Care; Torrance Memorial Medical Center; Gene Upshaw Memorial Tahoe Forest Cancer Center; City of Hope Upland; Kaiser Permanente-Vallejo; Kaiser Permanente-Walnut Creek; BASS Medical Group - Lennon; John Muir Medical Center-Walnut Creek; UCHealth University of Colorado Hospital; Rocky Mountain Cancer Centers-Boulder; UCHealth Memorial Hospital Central; Memorial Hospital North; Shaw Cancer Center; Poudre Valley Hospital; Cancer Care and Hematology-Fort Collins; Saint Mary's Hospital and Regional Medical Center; Banner North Colorado Medical Center; UCHealth Greeley Hospital; UCHealth Highlands Ranch Hospital; Medical Center of the Rockies; Banner North Colorado Medical Center - Loveland Campus; Hartford HealthCare - Saint Vincent's Medical Center; Smilow Cancer Hospital-Derby Care Center; Smilow Cancer Hospital Care Center-Fairfield; Smilow Cancer Hospital Care Center at Greenwich; Smilow Cancer Hospital Care Center - Guilford; Hartford Hospital; Smilow Cancer Hospital Care Center at Saint Francis; Midstate Medical Center; The Hospital of Central Connecticut; Yale University; Yale-New Haven Hospital North Haven Medical Center; Smilow Cancer Hospital-Orange Care Center; Smilow Cancer Hospital Care Center at Long Ridge; Stamford Hospital/Bennett Cancer Center; Smilow Cancer Hospital Care Center-Trumbull; Smilow Cancer Hospital Care Center - Waterford; Bayhealth Hospital Kent Campus; Helen F Graham Cancer Center; Medical Oncology Hematology Consultants PA; Mount Sinai Comprehensive Cancer Center at Aventura; Bay Pines VA Healthcare System; Boca Raton Regional Hospital; UF Health Cancer Institute - Gainesville; Mayo Clinic in Florida; GenesisCare USA - Lakewood Ranch; Miami Cancer Institute; Mount Sinai Medical Center; GenesisCare USA - Plantation; Miami Cancer Institute at Plantation; Tampa General Hospital; Grady Health System; Emory Proton Therapy Center; Emory University Hospital Midtown; Emory University Hospital/Winship Cancer Institute; Emory Saint Joseph's Hospital; Emory Decatur Hospital; Emory Johns Creek Hospital; Lewis Cancer and Research Pavilion at Saint Joseph's/Candler; Hawaii Cancer Care Inc - Waterfront Plaza; Queen's Cancer Cenrer - POB I; Queen's Medical Center; Straub Clinic and Hospital; University of Hawaii Cancer Center; Queen's Cancer Center - Kuakini; The Cancer Center of Hawaii-Liliha; Hawaii Cancer Care - Westridge; Pali Momi Medical Center; The Cancer Center of Hawaii-Pali Momi; The Queen's Medical Center - West Oahu; Alton Memorial Hospital; Rush-Copley Medical Center; Advocate Good Shepherd Hospital; Illinois CancerCare-Bloomington; Illinois CancerCare-Canton; Illinois CancerCare-Carthage; Northwestern University; Rush MD Anderson Cancer Center; University of Illinois; University of Chicago Comprehensive Cancer Center; Advocate Illinois Masonic Medical Center; AMG Crystal Lake - Oncology; Carle at The Riverfront; Decatur Memorial Hospital; Northwestern Medicine Cancer Center Kishwaukee; Advocate Good Samaritan Hospital; Crossroads Cancer Center; Advocate Sherman Hospital; Elmhurst Memorial Hospital; Illinois CancerCare-Eureka; Illinois CancerCare-Galesburg; Northwestern Medicine Cancer Center Delnor; Northwestern Medicine Glenview Outpatient Center; Northwestern Medicine Grayslake Outpatient Center; Ingalls Memorial Hospital; Advocate South Suburban Hospital; Edward Hines Jr VA Hospital; Illinois CancerCare-Kewanee Clinic; Northwestern Medicine Lake Forest Hospital; AMG Libertyville - Oncology; Condell Memorial Hospital; Illinois CancerCare-Macomb; Carle Physician Group-Mattoon/Charleston; Loyola University Medical Center; Edward Hospital/Cancer Center; UC Comprehensive Cancer Center at Silver Cross; HSHS Saint Elizabeth's Hospital; Northwestern Medicine Oak Brook; Advocate Christ Medical Center; Northwestern Medicine Orland Park; University of Chicago Medicine-Orland Park; Illinois CancerCare-Ottawa Clinic; Advocate High Tech Medical Park; Advocate Lutheran General Hospital; Illinois CancerCare-Pekin; Illinois CancerCare-Peoria; Methodist Medical Center of Illinois; OSF Saint Francis Medical Center; Illinois CancerCare-Peru; Edward Hospital/Cancer Center?Plainfield; Illinois CancerCare-Princeton; UW Health Carbone Cancer Center Rockford; Memorial Hospital East; Springfield Memorial Hospital; Carle Cancer Center; Northwestern Medicine Cancer Center Warrenville; Illinois CancerCare - Washington; IU Health West Hospital; IU Health North Hospital; UChicago Medicine Northwest Indiana; Indiana University/Melvin and Bren Simon Cancer Center; IU Health Methodist Hospital; UI Health Care Mission Cancer and Blood - Ankeny Clinic; Saint Luke's Hospital; Mercy Hospital; Oncology Associates at Mercy Medical Center; Iowa Methodist Medical Center; UI Health Care Mission Cancer and Blood - Des Moines Clinic; Broadlawns Medical Center; University of Kansas Cancer Center; The University of Kansas Cancer Center - Olathe; University of Kansas Cancer Center-Overland Park; Salina Regional Health Center; University of Kansas Health System Saint Francis Campus; University of Kansas Hospital-Westwood Cancer Center; Ascension Via Christi Hospitals Wichita; Wesley Medical Center; Saint Joseph Hospital East; The James Graham Brown Cancer Center at University of Louisville; UofL Health Medical Center Northeast; Mary Bird Perkins Cancer Center; Mary Bird Perkins Cancer Center - Metairie; East Jefferson General Hospital; LSU Healthcare Network / Metairie Multi-Specialty Clinic; Tulane University School of Medicine; MaineHealth Coastal Cancer Treatment Center; MaineHealth Maine Medical Center - Portland; Penobscot Bay Medical Center; MaineHealth Cancer Care Center of York County; MaineHealth Maine Medical Center- Scarborough; MaineHealth Cancer Care and IV Therapy - South Portland; Luminis Health Anne Arundel Medical Center; Maryland Proton Treatment Center; University of Maryland/Greenebaum Cancer Center; Veterans Administration Medical Center-Baltimore; Johns Hopkins University/Sidney Kimmel Cancer Center; UM Upper Chesapeake Medical Center; Suburban Hospital; University of Maryland Shore Medical Center at Easton; UM Baltimore Washington Medical Center/Tate Cancer Center; UM Capital Region Medical Center; Massachusetts General Hospital Cancer Center; Brigham and Women's Hospital; Boston Medical Center; Dana-Farber Cancer Institute; Cape Cod Hospital; Dana-Farber/Brigham and Women's Cancer Center at Milford Regional; Dana-Farber/Brigham and Women's Cancer Center at South Shore; Trinity Health Saint Joseph Mercy Hospital Ann Arbor; University of Michigan Rogel Cancer Center; McLaren Cancer Institute-Bay City; Trinity Health IHA Medical Group Hematology Oncology - Brighton; Trinity Health Medical Center - Brighton; University of Michigan - Brighton Center for Specialty Care; Henry Ford Cancer Institute-Downriver; Trinity Health IHA Medical Group Hematology Oncology - Canton; Trinity Health Medical Center - Canton; Chelsea Hospital; Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital; McLaren Cancer Institute-Clarkston; Michigan Healthcare Professionals Clarkston; Henry Ford Macomb Hospital-Clinton Township; Corewell Health Dearborn Hospital; Henry Ford Medical Center-Fairlane; Wayne State University/Karmanos Cancer Institute; Henry Ford Hospital; Michigan Healthcare Professionals Farmington; Weisberg Cancer Treatment Center; Genesys Hurley Cancer Institute; McLaren Cancer Institute-Flint; Corewell Health Grand Rapids Hospitals - Butterworth Hospital; Trinity Health Grand Rapids Hospital; Bronson Methodist Hospital; West Michigan Cancer Center; Karmanos Cancer Institute at McLaren Greater Lansing; University of Michigan Health - Sparrow Lansing; McLaren Cancer Institute-Lapeer Region; Trinity Health Saint Mary Mercy Livonia Hospital; Michigan Healthcare Professionals Macomb; Michigan Healthcare Professionals Madison Heights; McLaren Cancer Institute-Macomb; McLaren Cancer Institute-Central Michigan; Corewell Health Lakeland Hospitals - Niles Hospital; Henry Ford Medical Center-Columbus; McLaren-Port Huron; Corewell Health William Beaumont University Hospital; MyMichigan Medical Center Saginaw; Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center; Corewell Health Lakeland Hospitals - Saint Joseph Hospital; Henry Ford Macomb Health Center - Shelby Township; Munson Medical Center; Corewell Health Beaumont Troy Hospital; Michigan Healthcare Professionals Troy; Henry Ford West Bloomfield Hospital; University of Michigan Health - West; Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus; Mayo Clinic Health System in Albert Lea; Mercy Hospital; Miller-Dwan Hospital; Unity Hospital; Saint John's Hospital - Healtheast; Abbott-Northwestern Hospital; Hennepin County Medical Center; Monticello Cancer Center; Mayo Clinic in Rochester; Park Nicollet Clinic - Saint Louis Park; Regions Hospital; University of Mississippi Medical Center; Saint Francis Medical Center; Siteman Cancer Center at Saint Peters Hospital; MU Health - University Hospital/Ellis Fischel Cancer Center; Siteman Cancer Center at West County Hospital; Parkland Health Center - Farmington; Freeman Health System; University of Kansas Cancer Center - North; University of Kansas Cancer Center - Lee's Summit; University of Kansas Cancer Center at North Kansas City Hospital; Phelps Health Delbert Day Cancer Institute; Sainte Genevieve County Memorial Hospital; Mercy Hospital Springfield; Washington University School of Medicine; Siteman Cancer Center-South County; Missouri Baptist Medical Center; Siteman Cancer Center at Christian Hospital; Mercy Hospital Saint Louis; Missouri Baptist Sullivan Hospital; BJC Outpatient Center at Sunset Hills; Billings Clinic Cancer Center; Benefis Sletten Cancer Institute; Nebraska Medicine-Bellevue; Nebraska Medicine-Village Pointe; University of Nebraska Medical Center; New Hampshire Oncology Hematology PA-Concord; Exeter Hospital; Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center; Solinsky Center for Cancer Care; Clara Maass Medical Center; Cooper Hospital University Medical Center; AtlantiCare Surgery Center; Trinitas Hospital and Comprehensive Cancer Center - Williamson Street Campus; Englewood Hospital and Medical Center; The Cancer Institute of New Jersey Hamilton; Jersey City Medical Center; Saint Barnabas Medical Center; Rutgers Cancer Institute of New Jersey; Rutgers New Jersey Medical School; Newark Beth Israel Medical Center; The Valley Hospital - Luckow Pavilion; Valley Health System Ridgewood Campus; Sidney Kimmel Cancer Center Washington Township; Robert Wood Johnson University Hospital Somerset; Community Medical Center; MD Anderson Cancer Center at Cooper-Voorhees; Lovelace Medical Center-Saint Joseph Square; University of New Mexico Cancer Center; Lovelace Radiation Oncology; Presbyterian Kaseman Hospital; Presbyterian Rust Medical Center/Jorgensen Cancer Center; Northwell Health Imbert Cancer Center; New York-Presbyterian/Brooklyn Methodist Hospital; Roswell Park Cancer Institute; Sands Cancer Center; Mary Imogene Bassett Hospital; Noyes Memorial Hospital/Myers Cancer Center; The New York Hospital Medical Center of Queens; Northwell Health Physicians Partners Radiation Medicine at Queens; Glens Falls Hospital; Northwell Health Cancer Institute at Huntington; Northwell Health/Center for Advanced Medicine; Laura and Isaac Perlmutter Cancer Center at NYU Langone; NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center; Manhattan Eye Ear and Throat Hospital; NYP/Weill Cornell Medical Center; Lenox Hill Hospital; Queens Cancer Center; Highland Hospital; University of Rochester; Phelps Memorial Hospital Center; Staten Island University Hospital; Stony Brook University Medical Center; State University of New York Upstate Medical University; Montefiore Medical Center-Einstein Campus; Montefiore Medical Center - Moses Campus; Westchester Medical Center; Wilmot Cancer Institute at Webster; Duke Cancer Center Cary; Carolinas Medical Center/Levine Cancer Institute; Novant Health Presbyterian Medical Center; Atrium Health Pineville/LCI-Pineville; Atrium Health University City/LCI-University; Levine Cancer Institute-Ballantyne; Atrium Health Cabarrus/LCI-Concord; Durham VA Medical Center; Duke University Medical Center; Novant Health Cancer Institute - Huntersville; Novant Health Presbyterian Medical Center Huntersville; Matthews Radiation Oncology Center; Novant Health Cancer Institute - Matthews; Atrium Health Union/LCI-Union; Novant Health Cancer Institute - Mooresville; UNC Health Cancer Care Raleigh; Duke Cancer Center Raleigh; UNC Health Cancer Care Wakefield; Novant Cancer Institute Radiation Oncology - Supply; Novant Health Cancer Institute Radiation Oncology - Wilmington; Novant Health New Hanover Regional Medical Center; Novant Health Forsyth Medical Center; Wake Forest University Health Sciences; Altru Cancer Center; Summa Health System - Akron Campus; Cleveland Clinic Akron General; Summa Health System - Barberton Campus; Aultman Health Foundation; Adena Regional Medical Center; The Christ Hospital; MetroHealth Medical Center; Ohio State University Comprehensive Cancer Center; Riverside Methodist Hospital; Grant Medical Center; Doctors Hospital; Delaware Health Center-Grady Cancer Center; Dublin Methodist Hospital; OhioHealth Mansfield Hospital; OhioHealth Marion General Hospital; Summa Health Medina Medical Center; ProMedica Flower Hospital; Cancer Centers of Southwest Oklahoma Research; University of Oklahoma Health Sciences Center; Saint Charles Health System; Legacy Mount Hood Medical Center; Providence Willamette Falls Medical Center; Legacy Good Samaritan Hospital and Medical Center; Providence Portland Medical Center; Providence Saint Vincent Medical Center; Legacy Meridian Park Hospital; Saint Luke's Cancer Center - Allentown; UPMC Altoona; UPMC-Heritage Valley Health System Beaver; Saint Luke's University Hospital-Bethlehem Campus; Crozer-Keystone Regional Cancer Center at Broomall; Carlisle Regional Cancer Center; Christiana Care Health System-Concord Health Center; Chambersburg Hospital; Geisinger Medical Center; Delaware County Memorial Hospital; Saint Luke's Hospital-Anderson Campus; Ephrata Cancer Center; UPMC Hillman Cancer Center Erie; Saint Vincent Hospital; UPMC Cancer Center at UPMC Horizon; Adams Cancer Center; Crozer Regional Cancer Center at Brinton Lake; UPMC Cancer Centers - Arnold Palmer Pavilion; UPMC Pinnacle Cancer Center/Community Osteopathic Campus; Penn State Milton S Hershey Medical Center; IRMC Cancer Center; Jefferson Hospital; UPMC-Johnstown/John P. Murtha Regional Cancer Center; Sechler Family Cancer Center; Geisinger Medical Oncology-Lewisburg; UPMC Cancer Center at UPMC McKeesport; Yolanda G Barco Oncology Institute; UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion; Forbes Hospital; UPMC Cancer Center - Monroeville; UPMC Hillman Cancer Center in Coraopolis; Thomas Jefferson University Hospital; Temple University Hospital; Einstein Medical Center Philadelphia; Allegheny General Hospital; UPMC-Magee Womens Hospital; UPMC-Saint Margaret; West Penn Hospital; University of Pittsburgh Cancer Institute (UPCI); UPMC-Shadyside Hospital; UPMC-Passavant Hospital; UPMC-Saint Clair Hospital Cancer Center; Geisinger Cancer Services-Pottsville; Saint Luke's Hospital - Upper Bucks Campus; Saint Luke's Hospital-Quakertown Campus; UPMC Cancer Center at UPMC Northwest; Saint Luke's Hospital - Monroe Campus; UPMC Cancer Center-Uniontown; UPMC Uniontown Hospital Radiation Oncology; UPMC Cancer Center-Washington; UPMC Washington Hospital Radiation Oncology; Chester County Hospital; Reading Hospital; Wexford Health and Wellness Pavilion; Geisinger Wyoming Valley/Henry Cancer Center; Divine Providence Hospital; Asplundh Cancer Pavilion; WellSpan Health-York Cancer Center; UPMC Memorial; Rhode Island Hospital; Smilow Cancer Hospital Care Center - Westerly; Saint Joseph's/Candler - Bluffton Campus; Medical University of South Carolina; MUSC Health Florence Medical Center; Saint Francis Hospital; Saint Francis Cancer Center; Self Regional Healthcare; Gibbs Cancer Center-Pelham; The Radiation Oncology Center-Hilton Head/Bluffton; Carolina Regional Cancer Center; Beaufort Memorial/New River Cancer Center; Spartanburg Medical Center; Covenant Health Cancer Centers; Covenant Health Oncology Group - Maryville; Covenant Health Oncology Group - Oak Ridge; Houston Methodist San Jacinto Hospital; MD Anderson in The Woodlands; Houston Methodist Hospital; M D Anderson Cancer Center; Methodist Willowbrook Hospital; MD Anderson West Houston; Houston Methodist West Hospital; MD Anderson League City; Texas Oncology-McKinney; Houston Methodist Saint John Hospital; University of Texas Health Science Center at San Antonio; MD Anderson in Sugar Land; Houston Methodist Sugar Land Hospital; Houston Methodist The Woodlands Hospital; American Fork Hospital / Huntsman Intermountain Cancer Center; Farmington Health Center; Logan Regional Hospital; Intermountain Medical Center; McKay-Dee Hospital Center; Utah Valley Regional Medical Center; Riverton Hospital; University of Utah Sugarhouse Health Center; Utah Cancer Specialists-Salt Lake City; Huntsman Cancer Institute/University of Utah; LDS Hospital; Saint George Regional Medical Center; Central Vermont Medical Center/National Life Cancer Treatment; University of Vermont Medical Center; Dartmouth Cancer Center - North; Inova Alexandria Hospital; Inova Schar Cancer Institute; Inova Fair Oaks Hospital; Bon Secours Saint Francis Medical Center; Bon Secours Cancer Institute at Reynolds Crossing; VCU Massey Comprehensive Cancer Center; Oncology and Hematology Associates of Southwest Virginia; Virginia Mason Medical Center; Legacy Cancer Institute Medical Oncology and Day Treatment; Legacy Salmon Creek Hospital; Providence Saint Mary Regional Cancer Center; West Virginia University Healthcare; Wheeling Hospital/Schiffler Cancer Center; Langlade Hospital and Cancer Center; ThedaCare Regional Cancer Center; Ascension Saint Elizabeth Hospital; Northwest Wisconsin Cancer Center; Ascension Southeast Wisconsin Hospital - Elmbrook Campus; Aurora Cancer Care-Southern Lakes VLCC; Ascension Calumet Hospital; HSHS Sacred Heart Hospital; Marshfield Medical Center-EC Cancer Center; Ascension Saint Francis - Reiman Cancer Center; Aurora Health Care Germantown Health Center; Aurora Cancer Care-Grafton; Saint Vincent Hospital Cancer Center Green Bay; Saint Vincent Hospital Cancer Center at Saint Mary's; Aurora BayCare Medical Center; University of Wisconsin Carbone Cancer Center - Johnson Creek; Aurora Cancer Care-Kenosha South; Mayo Clinic Health System-Franciscan Healthcare; University of Wisconsin Carbone Cancer Center - Eastpark Medical Center; University of Wisconsin Carbone Cancer Center - University Hospital; Aurora Bay Area Medical Group-Marinette; Marshfield Medical Center-Marshfield; Froedtert Menomonee Falls Hospital; Ascension Columbia Saint Mary's Hospital Ozaukee; Aurora Cancer Care-Milwaukee; Ascension Columbia Saint Mary's Hospital - Milwaukee; Aurora Saint Luke's Medical Center; Medical College of Wisconsin; Aurora Sinai Medical Center; Zablocki Veterans Administration Medical Center; Marshfield Medical Center - Minocqua; Drexel Town Square Health Center; Ascension Mercy Hospital; Vince Lombardi Cancer Clinic - Oshkosh; Ascension All Saints Hospital; Aurora Cancer Care-Racine; Aspirus Cancer Care - James Beck Cancer Center; Marshfield Medical Center-Rice Lake; Saint Vincent Hospital Cancer Center at Sheboygan; Vince Lombardi Cancer Clinic-Sheboygan; Aspirus Cancer Care - Stevens Point; Marshfield Medical Center-River Region at Stevens Point; Saint Vincent Hospital Cancer Center at Sturgeon Bay; Aurora Medical Center in Summit; Vince Lombardi Cancer Clinic-Two Rivers; Aspirus Regional Cancer Center; Ascension Medical Group Southeast Wisconsin - Mayfair Road; Aurora Cancer Care-Milwaukee West; Aurora West Allis Medical Center; Froedtert West Bend Hospital/Kraemer Cancer Center; Marshfield Medical Center - Weston; Aspirus Cancer Care - Wisconsin Rapids; Arthur J E Child Comprehensive Cancer Centre; Ottawa Hospital and Cancer Center-General Campus; University Health Network-Princess Margaret Hospital; The Research Institute of the McGill University Health Centre (MUHC); CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ); Centre Hospitalier Universitaire de Sherbrooke-Fleurimont; Allan Blair Cancer Centre; Saskatoon Cancer Centre
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Enrollment: 2753
Age range: 18 Years - None
Sex: MALE

Summary:
This phase III trial compares less intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in treating patients with high risk prostate cancer and low gene risk score. This trial also compares more intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in patients with high risk prostate cancer and high gene risk score. Apalutamide may help fight prostate cancer by blocking the use of androgen by the tumor cells. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving a shorter hormone therapy treatment may work the same at controlling prostate cancer compared to the usual 24 month hormone therapy treatment in patients with low gene risk score. Adding apalutamide to the usual treatment may increase the length of time without prostate cancer spreading as compared to the usual treatment in patients with high gene risk score.

Eligibility criteria:
Inclusion Criteria:

* PRIOR TO STEP 1 REGISTRATION
* Pathologically proven diagnosis of adenocarcinoma of prostate cancer within 180 days prior to registration
* High-risk disease defined as having at least one or more of the following:

  * PSA \> 20 ng/mL prior to starting ADT

    * Note: Patients receiving a 5-alpha reductase inhibitor (ex. finasteride) at the time of enrollment are eligible. The baseline PSA value should be doubled for PSAs taken while on 5-alpha reductase inhibitors and the medication should be discontinued prior to randomization but a washout period is not required
  * cT3a-T4 by digital exam or imaging (American Joint Committee on Cancer \[AJCC\] 8th edition \[Ed.\])
  * Gleason score of 8-10
  * Node positive by conventional imaging with a short axis of at least 1.0 cm
* Appropriate stage for study entry based on the following diagnostic workup:

  * History/physical examination within 120 days prior to registration;
  * Bone imaging within 120 days prior to registration;

    * Note: To be eligible, patient must have no definitive evidence of bone metastases (M0) on bone scan or sodium fluoride (NaF) PET within 120 days prior to registration (negative NaF PET/CT or negative Axumin or choline PET or negative fluciclovine, choline or prostate-specific membrane antigen (PSMA) PET within 120 days prior to registration is an acceptable substitute if they have been performed). Patients who have bone metastases established only fluciclovine, choline, or PSMA PET but not definitive on bone scan or NaF PET will still be eligible
  * CT or MRI of the pelvis within 120 days prior to registration (negative fluciclovine, choline, or PSMA PET within 120 days prior to registration is an acceptable substitute). As with bone staging, nodal staging for trial purposes will be based off of conventional imaging findings only
  * Patients with confirmed N1 metastases on conventional imaging (CT/MRI) as defined by \>= 10 mm on short axis are eligible but will be automatically assigned to the intensification study. Patients who are positive by fluciclovine, choline, or PSMA PET (i.e. N1), but whose nodes do not meet traditional size criteria for positivity (i.e. they measure \>= 10 mm on either the CT or MRI portion of the PET or on a dedicated CT or MRI) will not be considered N1 for the trial and will not automatically be assigned to the intensification study
* Age \>= 18
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days prior to registration
* Hemoglobin \>= 9.0 g/dL, independent of transfusion and/or growth factors (within 120 days prior to registration)
* Platelet count \>= 100 x 10\^3/uL independent of transfusion and/or growth factors (within 120 days prior to registration)
* Creatinine clearance (CrCl) \>= 30 mL/min estimated by Cockcroft-Gault equation (within 120 days prior to registration)

  * For Black patients whose renal function is not considered adequate by Cockcroft-Gault formula, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) may be used for calculating creatinine clearance for trial eligibility
  * Either a CrCl \>= 30 ml/min or calculated glomerular filtration rate (GFR) \>= 30 will make a patient eligible
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (within 120 days prior to registration)

  * Note: In subjects with Gilbert's syndrome, if total bilirubin is \> 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =\< 1.5 x ULN, subject is eligible
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (within 120 days prior to registration)
* Serum albumin \>= 3.0 g/dL (within 120 days prior to registration)
* The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial and have a CD4 count \>= 200 cells/microliter within 60 days prior to registration. Note: HIV testing is not required for eligibility for this protocol. Of note, for patients with HIV in the intensification trial randomized to apalutamide, highly active antiretroviral therapy (HAART) may need to be adjusted to medications that do not interact with apalutamide
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable after or on suppressive therapy within 60 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ or low-grade non-muscle invasive bladder cancer) who has been disease-free for less than 3 years must contact the principal investigator
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
* PRIOR TO STEP 2 RANDOMIZATION
* Confirmation of Decipher score
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 60 days prior. Note: Apalutamide may interfere with HCV drugs. Patients on HCV medications should alert their infectious diseases physician if they get randomized to apalutamide due to the possibility that apalutamide can affect the bioavailability of some HCV medications. HCV viral testing is not required for eligibility for this protocol
* For patients entering the Intensification Cohort ONLY: Patients must discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to Step 2 randomization

Exclusion Criteria:

* PRIOR TO STEP 1 REGISTRATION:
* Definitive radiologic evidence of metastatic disease outside of the pelvic nodes (M1a, M1b or M1c) on conventional imaging (i.e. bone scan, CT scan, MRI)
* Prior systemic chemotherapy within =\< 3 years prior to registration; note that prior chemotherapy for a different cancer is allowed (completed \> 3 years prior to registration
* Prior radical prostatectomy
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* Current use of 5-alpha reductase inhibitor. NOTE: If the alpha reductase inhibitor is stopped prior to randomization the patient is eligible
* History of any of the following:

  * Seizure disorder
  * Current severe or unstable angina
  * New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
  * History of any condition that in the opinion of the investigator, would preclude participation in this study
* Evidence of any of the following at registration:

  * Active uncontrolled infection requiring IV antibiotics
  * Baseline severe hepatic impairment (Child Pugh Class C)
  * Inability to swallow oral pills
  * Any current condition that in the opinion of the investigator, would preclude participation in this study
* Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both luteinizing hormone-releasing hormone \[LHRH\] agonist and oral anti-androgen) is =\< 60 days prior to registration; Please note: baseline PSA must be obtained prior to the start of any ADT
* PRIOR TO STEP 2 RANDOMIZATION:
* Evidence of known gastrointestinal disorder affecting absorption of oral medications at registration
* For patients entering the Intensification Cohort ONLY: Presence of uncontrolled hypertension (persistent systolic blood pressure \[BP\] \>= 160 mmHg or diastolic BP \>= 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment

Outcomes:
Metastasis-free survival (MFS); Sexual quality of life (De-intensification study); Hormonal quality of life (De-intensification study); Fatigue (Intensification study)