Prostate Cancer
Conditions
Keywords
stage II prostate cancer, adenocarcinoma of the prostate
Brief summary
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.
Detailed description
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.
Interventions
PROCEDUREconventional surgery
Radical prostatectomy
RADIATIONbrachytherapy
high dose rate temporary seed implant; permanent seed implant.
RADIATIONexternal beam radiation therapy
3D conformal radiation therapy; intensity modulated radiation therapy.
PROCEDUREBiopsies
Periodic repeat biopsies
Sponsors
National Cancer Institute (NCI)
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
SWOG Cancer Research Network
Radiation Therapy Oncology Group
Institute of Cancer Research, United Kingdom
NCIC Clinical Trials Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-specific Survival | 5 years 6 months | Time from the date of randomization to the date of death due to prostate cancer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 5 years 6 months | Time from randomization to the date of death due to any causes. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Surveillance Active surveillance with radical intervention at the time one or more of the following occur: Biochemical progression; Grade progression; Clinical progression | 78 |
| Radical Intervention Radical prostatectomy or radiotherapy based on patient and physician preference
conventional surgery: Radical prostatectomy
brachytherapy: high dose rate temporary seed implant; permanent seed implant.
external beam radiation therapy: 3D conformal radiation therapy; intensity modulated radiation therapy.
Biopsies: Periodic repeat biopsies | 102 |
| Total | 180 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 78 | 9 |
Baseline characteristics
| Characteristic | Active Surveillance | Radical Intervention | Total |
|---|---|---|---|
| Age, Customized age group : 40-49 | 0 years | 2 years | 2 years |
| Age, Customized age group : 50-59 | 9 years | 22 years | 31 years |
| Age, Customized age group : 60-69 | 48 years | 56 years | 104 years |
| Age, Customized age group : >= 70 | 21 years | 20 years | 41 years |
| Age, Customized age group : Missing | 0 years | 1 years | 1 years |
| Disease Stage* T1B | 1 participants | 0 participants | 1 participants |
| Disease Stage* T1C | 64 participants | 79 participants | 143 participants |
| Disease Stage* T2A | 12 participants | 20 participants | 32 participants |
| Disease Stage* T2B | 1 participants | 3 participants | 4 participants |
| ECOG Performance Status* 0 | 73 participants | 98 participants | 171 participants |
| ECOG Performance Status* 1 | 5 participants | 4 participants | 9 participants |
| Gleason Score (Combined)* 6 | 78 Participants | 102 Participants | 180 Participants |
| Gleason Score (Combined)* Other | 0 Participants | 0 Participants | 0 Participants |
| PSA value < 5. ug/L | 43 participants | 55 participants | 98 participants |
| PSA value >= 5. ug/L | 35 participants | 47 participants | 82 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 78 Participants | 102 Participants | 180 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 78 | 2 / 99 |
| other Total, other adverse events | 57 / 78 | 65 / 99 |
| serious Total, serious adverse events | 0 / 78 | 0 / 99 |
Outcome results
Primary
Disease-specific Survival
Time from the date of randomization to the date of death due to prostate cancer.
Time frame: 5 years 6 months
Population: Due to difficulty in accruing patients to the trial, the trial was closed early, there is no patient died of prostate cancer. Thus, no analysis was done.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radical Intervention | Disease-specific Survival | NA years |
| Active Surveillance | Disease-specific Survival | NA years |
Secondary
Overall Survival
Time from randomization to the date of death due to any causes.
Time frame: 5 years 6 months
Population: Due to lower patients accrual rate, the trial was closed early with only 3 events reported in the trial, Thus.no formal analysis had been done.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radical Intervention | Overall Survival | NA years |
| Active Surveillance | Overall Survival | NA years |