Androgen-Deprivation Therapy and Radiation Therapy in Treating Patients With Prostate Cancer

OBJECTIVES: Primary * Demonstrate that prophylactic, neoadjuvant androgen-deprivation therapy (NADT) combined with whole-pelvic radiation therapy (WPRT) improves overall survival (OS) compared with NADT combined with prostate and seminal vesicle radiation therapy (RT), with both arms receiving a high-dose prostate boost delivered by intensity-modulated RT (IMRT), external-beam RT (EBRT), high-dose-rate (HDR) brachytherapy, or permanent prostate implant (PPI). Secondary * Demonstrate that prophylactic WPRT improves biochemical control. * Determine the distant metastasis (DM)-free survival. * Determine the cause-specific survival (CSS). * Compare acute and late treatment-adverse events between patients receiving NADT and WPRT versus NADT, P, and SV RT. * Determine whether health-related quality of life (HRQOL), as measured by the Expanded Prostate Cancer Index Composite (EPIC), significantly worsens with increasing aggressiveness of treatment (i.e., Arm 2, NADT + WPRT). * Determine whether more aggressive treatment (Arm 2, NADT + WPRT) is associated with a greater increase in fatigue (PROMIS Fatigue Short Form) from baseline to last week of treatment, and a greater increase in circulating inflammatory markers (IL-1, IL-1ra, IL-6, tumor necrosis factor (TNF)-alpha, and C-reactive protein). * Demonstrate an incremental gain in OS and CSS with more aggressive therapy that outweighs any detriments in the primary generic domains of HRQOL (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). * Determine whether changes in fatigue from baseline to the next three time points (week prior to RT, last week of treatment, and 3 months after treatment) are associated with changes in circulating cytokines, mood, sleep, and daily activities across the same time points. * Collect paraffin-embedded tissue blocks, plasma, whole blood, and urine for planned and future translational research analyses. OUTLINE: This is a multicenter study. Patients are stratified according to moderate- to high-risk groups as listed in the Disease Characteristics of this abstract, type of radiotherapy boost (IMRT vs brachytherapy \[Low-dose rate (LDR) using PPI or HDR\]), and duration of androgen-deprivation therapy (short-term \[4-6 months\] vs long-term \[32 months\]). Patients are randomized to 1 of 2 treatment arms. All patients receive neoadjuvant androgen-deprivation therapy comprising bicalutamide orally (PO) once daily or flutamide PO thrice daily for 4-6 months, and luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy comprising leuprolide acetate, goserelin acetate, buserelin, triptorelin, or degarelix subcutaneously (SC) or intramuscularly (IM) every 1 to 3 months beginning 2 months prior to radiotherapy and continuing for 4-6 or 32 months. Radiotherapy begins within 8 weeks after beginning LHRH agonist/antagonist injection. Patients may undergo blood and urine sample collection for correlative studies. Primary tumor tissue samples may also be collected. Patients may complete the Expanded Prostate Cancer Index Composite (EPIC), the PROMIS-Fatigue Short Form, and the EuroQol (EQ-5D) quality-of-life (QOL) questionnaires at baseline and periodically during treatment. Patients who participate in the QOL portion of the study must also agree to periodic blood collection. After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 3 years, and then yearly thereafter.