Androgen Deprivation Therapy in Treating Patients With Prostate Cancer

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

RATIONALE: Androgens can cause the growth of prostate cancer cells. Androgen deprivation therapy may stop the adrenal glands from making androgens.

PURPOSE: This randomized phase III trial is studying how well androgen deprivation therapy works in treating patients with prostate cancer.

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.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

• Prostate-specific antigen (PSA) relapse OR incurable disease diagnosed within the past 2 months AND meets criteria for either of the following groups:

  • Group 1

    • In PSA relapse after definitive radical treatment (prostatectomy or radiotherapy), as evidenced by 1 the following:

      • Post-prostatectomy PSA level ≥ 0.2 ng/mL
      • At least 3 rising PSA levels (post-radiotherapy) obtained ≥ 1 month apart, with the last PSA obtained within the past 2 months

    • No metastatic disease by bone scan or abdomino-pelvic CT scan

  • Group 2

    • Not suitable for radical treatment at primary diagnosis

    • Not planning to receive curative treatment

    • Localized or metastatic disease

      • No symptomatic disease requiring radiotherapy or immediate hormonal therapy

• No symptomatic disease requiring therapy

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• Not specified

Life expectancy

• At least 5 years

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• No other significant comorbid condition that would limit life expectancy to < 5 years

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• At least 12 months since prior androgen deprivation therapy (ADT) administered in the neoadjuvant or concurrent (with radiotherapy) setting (group 1)
• No prior ADT (group 2)

Radiotherapy

• See Disease Characteristics
• See Endocrine therapy

Surgery

• See Disease Characteristics

Other

• No concurrent enrollment in TROG-96.01 or TROG-RADAR protocols