A Collaborative Randomized Phase III Trial: The Timing of Intervention With Androgen Deprivation in Prostate Cancer Patients With Rising PSA

Brief Summary

Detailed Description

OBJECTIVES: Primary * Compare overall survival (with acceptable morbidity) of patients with prostate cancer treated with delayed vs immediate androgen deprivation therapy (ADT). Secondary * Compare cancer-specific survival of patients treated with these regimens. * Compare clinical progression in patients treated with these regimens. * Compare time to first androgen independence in patients treated with these regimens. * Compare complication rate incidence and timing (e.g., cord compression or pathological failure) in patients treated with these regimens. * Compare treatment-related morbidity (including cognitive morbidity or osteoporosis) in patients treated with these regimens. * Compare quality of life of patients treated with these regimens. * Determine prognostic factors for progression in patients treated with delayed ADT. OUTLINE: This is a multicenter, randomized, controlled study. Patients in group 1 are stratified according to prior therapy (prostatectomy vs radiotherapy vs prostatectomy and radiotherapy), relapse-free interval (\< 2 years vs ≥ 2 years), type of planned androgen deprivation therapy (ADT) (continuous vs intermittent), and participating center. Patients in group 2 are stratified according to type of planned ADT (continuous vs intermittent), disease type (localized vs metastatic), and participating center. Patients in both groups are randomized to 1 of 2 treatment arms. * Arm I (delayed ADT): Beginning at least 2 years after study entry or after exhibiting evidence of significant disease progression\*, patients receive either continuous ADT OR intermittent ADT comprising either bilateral orchiectomy OR luteinizing hormone-releasing hormone agonist with or without oral antiandrogen therapy. * Arm II (immediate ADT): Beginning immediately after randomization, patients receive either continuous ADT OR intermittent ADT as in arm I. NOTE: \*Patients in group 1 begin delayed ADT at least 2 years after study entry unless 1 of the following clinical criteria is present: prostate-specific antigen (PSA) doubling time of \< 12 months with PSA ≥ 10 ng/mL OR PSA doubling time of ≤ 6 months based on 3 consecutive measurements obtained ≥ 2 months apart OR development of metastases or symptoms. Patients in group 2 begin delayed ADT at least 2 years after study entry unless 1 of the following clinical criteria is present: development of symptoms OR PSA ≥ 60 ng/mL OR PSA doubling time of ≤ 6 months based on 3 consecutive measurements obtained ≥ 2 months apart. After 9 months of ADT, all patients are assessed for response. Patients with PSA \< 4 ng/mL may discontinue ADT. These patients are followed every 3 months. Treatment may be restarted when PSA is \> 20 ng/mL OR PSA is \> the PSA level at study entry OR at clinical progression. Quality of life is assessed at baseline, every 6 months for 2 years, and then annually for 3 years. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then periodically thereafter at the discretion of the principal investigator. PROJECTED ACCRUAL: A total of 300-2,000 patients will be accrued for this study within 2-5 years.

Primary Outcomes

Secondary Outcomes

• Cancer specific survival
• Clinical progression
• Time to first androgen independence
• Complication rate incidence and timing (e.g., cord compression, pathological fracture)
• Treatment-related morbidity (including cognitive, osteoporosis)
• Prognostic factors for progression (delayed group)
• EORTC Quality of life - general QLQC30 and prostate module for Quality of life annually for 5 years
• CTC v3.0 Survival endpoints: actuarial analysis at eight years
• Morbidity continuously