Observation or Radical Treatment in Patients With Prostate Cancer

A Phase III Study of Active Surveillance Therapy Against Radical Treatment in Patients Diagnosed With Favourable Risk Prostate Cancer [START]

RATIONALE: Sometimes prostate tumours may not need treatment until they progress. In this case, observation may be sufficient. Radical treatments, such as radical prostatectomy or radiation therapy, may be effective in treating prostate cancer when it is first diagnosed. It is not yet known whether active surveillance is more effective than radical treatment as an initial intervention in favorable prognosis prostate cancer.

PURPOSE: This randomized phase III trial is studying active surveillance to see how well it works compared with radical treatment as an initial intervention in patients with favorable prognosis prostate cancer.

OBJECTIVES:

Primary

• To compare disease-specific survival of patients with favorable risk prostate cancer treated with radical prostatectomy or radical radiotherapy at the time of initial diagnosis vs active surveillance and selective intervention based on pre-specified biochemical, histological, or clinical progression criteria.

Secondary

• To compare overall survival, quality of life using the EPIC-26, RAND SF-12, and State-Trait Anxiety Inventory, distant disease-free survival, PSA relapse/progression after radical intervention, and initiation of androgen deprivation therapy between the two treatment arms.
• To determine the proportion of patients on the active surveillance arm who receive radical intervention for prostate cancer.
• To determine if PSA doubling-time prior to diagnosis predicts eventual outcome.
• To determine if molecular biomarkers predict outcome.

OUTLINE: This is a prospective, randomized, multicenter study. Patients are stratified by treatment center, ECOG performance status (0 vs 1 or 2), disease stage (T1 vs T2), baseline PSA value (ng/mL or μg/L) (< 5.0 vs ≥ 5.0 and ≤ 10.0), and age (< 65 years vs ≥ 65 years). Patients are randomized to 1 of 2 arms.

• Arm I: Patients undergo radical intervention (radical prostatectomy or radiotherapy [external-beam radiotherapy 5 days a week for 4-8 weeks; permanent prostate brachytherapy; or high-dose rate temporary brachytherapy], based on patient and physician preference).
• Arm II: Patients undergo active surveillance with radical intervention at the time one or more pre-specified criteria (biochemical progression, histologic/grade progression, and/or clinical progression) are met.

Quality of life is assessed by the EPIC-26, RAND SF-12, and State Anxiety Inventory at baseline, periodically during study treatment, and after completion of radical treatment.

After completion of radical treatment, patients are followed every 6 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

  • Diagnosed within 6 months prior to randomization

• Patient has been classified as favorable risk as defined by the following:

  • Clinical stage T1b, T1c, T2a, or T2b at the time of diagnosis
  • Clinical (diagnostic biopsy) Gleason score ≤ 6
  • PSA ≤ 10.0 ng/mL

• Physical examination, rectal examination, and transrectal ultrasound have been done within 6 months prior to randomization and radiographic studies, if indicated, are negative for metastasis

• Patient is a suitable candidate for radical prostatectomy or radiotherapy

PATIENT CHARACTERISTICS:

• ECOG performance status 0, 1, or 2
• Patient has a minimum life expectancy of > 10 years
• In centers participating in the quality of life component of the study, the patient is able (i.e., sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French
• No history of other malignancies, except adequately treated non-melanoma skin cancer, adequately treated superficial bladder cancer, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years from study randomization

PRIOR CONCURRENT THERAPY:

• No previous treatment for prostate cancer, including surgery (excluding biopsy and TURP), radiotherapy, or androgen deprivation therapy for greater than 3 months
• No planned androgen therapy except in the context of radical therapy