An Efficacy and Safety Study of JNJ-56021927 (Apalutamide) in High-risk Prostate Cancer Subjects Receiving Primary Radiation Therapy: ATLAS

Inclusion Criteria:

* Age \>= 18 years
* Indicated and planned to receive primary radiation therapy for prostate cancer
* Histologically confirmed adenocarcinoma of an intact prostate, and 1 of the following at diagnosis: 1) Gleason score \>=8 and \>=cT2c, 2) Gleason score 7, PSA \>=20 nanogram per milliliters (ng/mL), and \>=cT2c
* Charlson index (CCI) \<=3
* An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade of 0 or 1
* Adequate organ function: (1) aspartate aminotransferase (AST), alanine aminotransferase (ALT), within normal limits (WNL), (2) serum creatinine less than (\<) 1.5 milligram/deciliter (mg/dL) (\<133 micromoles/Liter \[mcmol/L\]), (3) platelets greater than or equal to (\>=)140,000/microLiter (mcL), independent of transfusion and/or growth factors within 3 months prior to randomization, (4) Hemoglobin \>= 12.0 gram/deciliter (g/dL) (7.4 millimloes \[mmol\], independent of transfusion and/or growth factors within 3 months prior to randomization
* Participants who are sexually active (even men with vasectomies) and willing to use a condom and agree not to donate sperm during the trial
* Signed, written, informed consent
* Be able to swallow whole study drug tablets

Exclusion Criteria: -

* Presence of distant metastasis, (clinical stage M1). Isolated pelvic nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal disease (clinical N stage; N1 versus N0) will be assessed by central radiological review. Patients are considered eligible only if the central radiological review confirms clinical stage M0
* Prior treatment with gonadotropin releasing hormone (GnRH) analogue or anti-androgen or both for \>3 months prior to randomization
* Bilateral orchiectomy
* History of pelvic radiation
* Prior systemic (example \[e.g.\], chemotherapy) or local (e.g. radical prostatectomy, cryotherapy) treatment for prostate cancer
* History of seizure or any condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness \<= 1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
* Prior treatment with enzalutamide, abiraterone acetate, orteronel, galeterone, ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational agents (including cyproterone acetate) for prostate cancer
* Prior treatment with radiopharmaceutical agents (e.g., strontium-89) or immunotherapy (e.g., sipuleucel-T) for prostate cancer
* Prior treatment with systemic glucocorticoids ≤4 weeks prior to randomization or is expected to require long-term use of corticosteroids during the study
* Use of 5-alpha reductase inhibitors (e.g., dutasteride, finasteride) \<=4 weeks prior to randomization
* Use of any investigational agent \<=4 weeks prior to randomization
* Current chronic use of opioid analgesics for \>=3 weeks for oral or \>= 7 days for non-oral formulations
* Major surgery \<=4 weeks prior to randomization
* Current or prior treatment with anti-epileptic medications for the treatment of seizures
* Gastrointestinal conditions affecting absorption
* Known or suspected contraindications or hypersensitivity to apalutamide, bicalutamide or GnRH agonists or any of the components of the formulations
* Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject