Radiation Therapy With or Without Androgen-Deprivation Therapy in Treating Patients With Prostate Cancer

• Overall survival (OS) [ Time Frame: From the date of randomization to the date of death due to any cause. ] [ Designated as safety issue: No ]
  

• Biochemical failure according to the Phoenix (nadir + 2) definition [ Time Frame: From the date of randomization to the date of first documented rise in PSA of 2 ng/ml above the post treatment nadir value. ] [ Designated as safety issue: No ]
  
• Local recurrence [ Time Frame: From the date of randomization to the date of first palpable progression or pathologic confirmation of local progression or to the date of first biochemical failure (nadir +2ng/ml) once the possibility of distant metastasis is ruled out. ] [ Designated as safety issue: No ]
  
• Regional recurrence [ Time Frame: From the date of randomization to the date of first documented progression in pelvic lymph nodes or the date of first documented biochemical failure (BCF) if the CT of the pelvis was prompted by a BCF. ] [ Designated as safety issue: No ]
  
• Distant metastasis [ Time Frame: From the date of randomization to the date of first documented metastatic disease by any measure or to the date of first documented biochemical failure if diagnostic imaging is prompted by BCF. ] [ Designated as safety issue: No ]
  
• Prostate cancer-specific mortality [ Time Frame: From the date of randomization to the date of death due to prostate cancer/complication of treatment. ] [ Designated as safety issue: No ]
  
• Non-prostate cancer-specific mortality [ Time Frame: From the date of randomization to the date of death without the evidence of prostate cancer/complication of treatment. ] [ Designated as safety issue: No ]
  
• Rate of salvage androgen-deprivation therapy [ Time Frame: From the end of treatment to the date of first administration of ADT. ] [ Designated as safety issue: No ]
  
• Rates of OS for patients treated with the 3 different radiotherapy modalities in each arm [ Time Frame: From the date of randomization to the date of death due to any cause. ] [ Designated as safety issue: No ]
  
• Incidence of "acute" adverse events as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v. 4.0 [ Time Frame: From the start of radiation therapy (RT) to first occurrence of worse severity of adverse event within 30 days after the completion of RT. ] [ Designated as safety issue: Yes ]
  
• Time to "late" grade 3+ adverse events as assessed by NCI CTCAE v. 4.0 [ Time Frame: From the date of completion of RT to the date of first grade 3 or above adverse event occurring 30 days after the completion of RT. ] [ Designated as safety issue: Yes ]
  
• Freedom from Failure [ Time Frame: From date of randomization to the date of first event of biochemical failure or local recurrence or regional reccurrence or distant metastasis. ] [ Designated as safety issue: No ]
  
• Comparison of prostate cancer-specific health related quality of life (HRQOL) change as measured by EPIC [ Time Frame: From date of randomization to the following times: last week of RT, 6 months, 1 year and 5 years post RT. ] [ Designated as safety issue: No ]
  
• Comparison of fatigue status as measured by the Patient Reported Outcome Measurement Information System (PROMIS) fatigue domain [ Time Frame: From date of randomization to the following times: last week of RT, 6 months, 1 year and 5 years post RT. ] [ Designated as safety issue: No ]
  
• Assessment and comparison of Quality Adjusted Life Years (QALYs) [ Time Frame: From date of randomization to the following times: last week of RT, 6 months, 1 year and 5 years post RT. ] [ Designated as safety issue: No ]
  
• Correlation between the fatigue PROMIS score change and plasma cytokine change [ Time Frame: From date of randomization to 3 weeks from start of RT. ] [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Demonstrate an overall survival (OS) advantage in patients with intermediate-risk prostate cancer treated with dose-escalated radiotherapy (RT) with versus without short-term androgen-deprivation therapy (ADT).

Secondary

• Determine whether the addition of ADT to dose-escalated RT versus RT alone improves clinical failures, biochemical failure by the "nadir +2", freedom from failure, rate of salvage ADT, and prostate cancer-specific mortality in these patients.
• Estimate the magnitude of benefit of ADT with respect to OS in patients treated with different RT modalities (i.e., external-beam radiation therapy alone vs low-dose rate brachytherapy boost vs high-dose rate brachytherapy boost).
• Compare acute and late treatment adverse events of these regimens and correlate these events with the presence or absence of pre-existing comorbidity as documented by the Adult Comorbidity Evaluation 27 assessment.

OUTLINE: This is a multicenter, dose-escalation study of radiotherapy. Patients are stratified according to number of risk factors (1 vs 2-3), comorbidity (ACE-27 grade ≥ 2 vs < 2), and radiotherapy (RT) modality (dose-escalated external-beam RT [EBRT] vs EBRT and low-dose rate brachytherapy boost vs EBRT and high-dose rate brachytherapy boost). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo EBRT* once daily on days 1-5 for about 9 weeks (44 treatments). Some patients instead receive EBRT with high-dose rate or low-dose rate brachytherapy implant on days 1-5 for about 5 weeks (25 treatments). NOTE: *Type of RT is at discretion of treating physician and may include either 3D-conformal RT or intensity-modulated RT.
• Arm II: Patients receive androgen-deprivation therapy comprising luteinizing-hormone releasing-hormone (LHRH) agonist (leuprolide, goserelin, buserelin, or triptorelin) subcutaneously or as an injection every 1 to 3 months AND an oral antiandrogen therapy (flutamide 3 times daily or bicalutamide once daily) for 6 months. Beginning 8 weeks after the first LHRH injection, patients undergo radiotherapy as in arm I.

After completion of study therapy, patients are followed up periodically.