Prostate Adenocarcinoma
Conditions
Keywords
Patients with prostate adenocarcinoma
Brief summary
The present study is a phase III randomized and multicentric trial evaluating the potential additional impact effect of two years adjuvant androgen deprivation when combined with neoadjuvant (4 months) and high-dose (76 Gy) conformal radiotherapy in moderate high-risk prostate cancer patients. Stratification will be performed by prognostic factors and by participating institution.
Interventions
DRUGShort term androgen deprivation
* Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months) * Bicalutamide 50 mg tablet every day for 2 months
DRUGLong term androgen deprivation
* Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months) * Bicalutamide 50 mg tablet every day for 2 months * Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy
Sponsors
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
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
* Histological proven adenocarcinoma of the prostate * Stage: cT1c-3b N0M0 according to American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) * Prostatic Specific Antigen (PSA)\<100 ng/ml * Intermediate (T1-T2 with Gleason Score \[GS\] 7 and/or PSA 10-20) * High risk (T3 and/or GS 8-10 and/or PSA \> 20) * Karnofsky Index (KI) performance status ≥70% * Written informed consent
Exclusion criteria
* T4 N1 M1, * Previous surgical treatment (prostatectomy or cryosurgery) * Neoadjuvant hormonal treatment \> 3 months. * History of pelvic radiotherapy (RT) * Contraindications for radiotherapy * Concomitant use of chemotherapy * Serious psychiatric or medical condition * Current synchronic malignancies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biochemical Disease Free Survival: Estimated Percentage of Participants With Biochemical Disease-free Survival at 5 Years | 5 years | Biochemical relapse was defined as the time from inclusion in the study (randomization) until the patient meets criteria for Biochemical failure (Phoenix criteria: PSA nadir plus 2 ng/ml). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Metastasis Free Survival: Estimated Percentage of Participants With Metastasis-free Survival at 5 Years | 5 years | Metastasis free survival: defined as the time from inclusion in the study (randomization) until the appearance of distant metastases: a positive result in any of the tests performed (scintigraphy, chest radiography, thorax, abdominal and pelvic CT and MRI). |
| Overall Survival: Estimated Percentage of Participants Alive at 5 Years | 5 years | Overall Survival: defined as the time that elapses from the patient enters the study until the patient dies from any cause. |
| Cause-specific Survival | 5 years | Cause-specific survival included all deaths from prostate cancer or treatment complications, and deaths from unknown causes in patients with either active cancer or a previously documented relapse |
| Late Toxicity | 5 years | Defined as the maximal rectal, urinary and cardiovascular (CV) toxicity per patient more than 90 days after completion of RT. Scoring scales used were the radiation morbidity scoring criteria of the European Organization for Research and Treatment of Cancer-Radiation Therapy Oncology Group (EORTC/RTOG) and the Common Terminology Criteria for Adverse Events (CTCAEs) v 3.0 for the remained toxicity. CV events were defined according to the World Health Organization criteria |
Countries
Spain
Participant flow
Recruitment details
Between Nov 7, 2005, and Dec 20, 2010, 362 were registered. Of these, seven did not meet the inclusion criteria. The final trial population thus consisted of 355 men, of whom 178 were randomly assigned to the short-term androgen deprivation group and 177 to the long-term androgen deprivation group.
Participants by arm
| Arm | Count |
|---|---|
| Long Term Androgen Deprivation * Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months)
* Bicalutamide 50 mg tablet every day for 2 months
* High dose conformal radiotherapy
* Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy
Long term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months)
* Bicalutamide 50 mg tablet every day for 2 months
* Gosereline 10.8 mg by subcutaneous injection every 3 moths for 2 years at the end of the radiotherapy
Long term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy) | 177 |
| Short Term Androgen Deprivation * Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months)
* Bicalutamide 50 mg tablet every day for 2 months
* High dose conformal radiotherapy
Short term androgen deprivation: - Gosereline 3.6 mg 1 month plus 10.8 mg subcutaneously 3 months (total 4 months)
\- Bicalutamide 50 mg tablet every day for 2 months
Short term androgen deprivation: Minimum dose of 76 Gy (range 76-82 Gy) | 178 |
| Total | 355 |
Baseline characteristics
| Characteristic | Long Term Androgen Deprivation | Short Term Androgen Deprivation | Total |
|---|---|---|---|
| Age, Continuous | 71 Years | 72 Years | 71 Years |
| Gleason score (categorical) <=6 | 21 participants | 30 participants | 51 participants |
| Gleason score (categorical) 7 | 110 participants | 103 participants | 213 participants |
| Gleason score (categorical) 8-10 | 46 participants | 45 participants | 91 participants |
| Pelvic radiotherapy (categorical) Missing | 3 participants | 0 participants | 3 participants |
| Pelvic radiotherapy (categorical) No | 148 participants | 145 participants | 293 participants |
| Pelvic radiotherapy (categorical) Yes | 20 participants | 28 participants | 48 participants |
| Positive biopsy samples (continous) | 4 number of cylindres | 4 number of cylindres | 4 number of cylindres |
| Prostate radiotherapy dose (categorical) <78 Gy | 43 participants | 51 participants | 94 participants |
| Prostate radiotherapy dose (categorical) >= 78 Gy | 128 participants | 122 participants | 250 participants |
| Prostate radiotherapy dose (continous) | 78.0 Grays (Gy) | 78.0 Grays (Gy) | 78.0 Grays (Gy) |
| PSA (categorical) 10-20 ng/mL | 61 participants | 64 participants | 125 participants |
| PSA (categorical) <10 ng/mL | 80 participants | 74 participants | 154 participants |
| PSA (categorical) >20 ng/mL | 36 participants | 40 participants | 76 participants |
| PSA (continous) | 11.1 nanogrames per milliliter (ng/mL) | 11.0 nanogrames per milliliter (ng/mL) | 11 nanogrames per milliliter (ng/mL) |
| Risk subgroup (intermediate vs. high) High | 92 participants | 97 participants | 189 participants |
| Risk subgroup (intermediate vs. high) Intermediate | 85 participants | 81 participants | 166 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 177 Participants | 178 Participants | 355 Participants |
| T stage (categorical) T1: tumor neither palpable not visible by imaging | 38 participants | 42 participants | 80 participants |
| T stage (categorical) T2: Tumor confinent whitin prostate | 100 participants | 103 participants | 203 participants |
| T stage (categorical) T3: Tumor extends through the prostate capsule | 39 participants | 33 participants | 72 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 62 / 177 | 40 / 178 |
| serious Total, serious adverse events | 36 / 177 | 29 / 178 |
Outcome results
Primary
Biochemical Disease Free Survival: Estimated Percentage of Participants With Biochemical Disease-free Survival at 5 Years
Biochemical relapse was defined as the time from inclusion in the study (randomization) until the patient meets criteria for Biochemical failure (Phoenix criteria: PSA nadir plus 2 ng/ml).
Time frame: 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Long Term Androgen Deprivation | Biochemical Disease Free Survival: Estimated Percentage of Participants With Biochemical Disease-free Survival at 5 Years | 90 percentage of patients |
| Short Term Androgen Deprivation | Biochemical Disease Free Survival: Estimated Percentage of Participants With Biochemical Disease-free Survival at 5 Years | 81 percentage of patients |
p-value: 0.0195% CI: [1.12, 3.15]Regression, Cox
Secondary
Cause-specific Survival
Cause-specific survival included all deaths from prostate cancer or treatment complications, and deaths from unknown causes in patients with either active cancer or a previously documented relapse
Time frame: 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Long Term Androgen Deprivation | Cause-specific Survival | 177 participants |
| Short Term Androgen Deprivation | Cause-specific Survival | 173 participants |
Secondary
Late Toxicity
Defined as the maximal rectal, urinary and cardiovascular (CV) toxicity per patient more than 90 days after completion of RT. Scoring scales used were the radiation morbidity scoring criteria of the European Organization for Research and Treatment of Cancer-Radiation Therapy Oncology Group (EORTC/RTOG) and the Common Terminology Criteria for Adverse Events (CTCAEs) v 3.0 for the remained toxicity. CV events were defined according to the World Health Organization criteria
Time frame: 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Long Term Androgen Deprivation | Late Toxicity | Grade 2 of more rectal toxicity | 11.1 percentage of patients |
| Long Term Androgen Deprivation | Late Toxicity | Grade 2 of more urinary toxicity | 8.2 percentage of patients |
| Long Term Androgen Deprivation | Late Toxicity | Cardiovascular | 17.6 percentage of patients |
| Short Term Androgen Deprivation | Late Toxicity | Grade 2 of more rectal toxicity | 7.6 percentage of patients |
| Short Term Androgen Deprivation | Late Toxicity | Grade 2 of more urinary toxicity | 7.3 percentage of patients |
| Short Term Androgen Deprivation | Late Toxicity | Cardiovascular | 7.2 percentage of patients |
Secondary
Metastasis Free Survival: Estimated Percentage of Participants With Metastasis-free Survival at 5 Years
Metastasis free survival: defined as the time from inclusion in the study (randomization) until the appearance of distant metastases: a positive result in any of the tests performed (scintigraphy, chest radiography, thorax, abdominal and pelvic CT and MRI).
Time frame: 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Long Term Androgen Deprivation | Metastasis Free Survival: Estimated Percentage of Participants With Metastasis-free Survival at 5 Years | 94 percentage of participants |
| Short Term Androgen Deprivation | Metastasis Free Survival: Estimated Percentage of Participants With Metastasis-free Survival at 5 Years | 83 percentage of participants |
p-value: 0.0195% CI: [1.23, 3.85]Regression, Cox
Secondary
Overall Survival: Estimated Percentage of Participants Alive at 5 Years
Overall Survival: defined as the time that elapses from the patient enters the study until the patient dies from any cause.
Time frame: 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Long Term Androgen Deprivation | Overall Survival: Estimated Percentage of Participants Alive at 5 Years | 95 percentage of patients |
| Short Term Androgen Deprivation | Overall Survival: Estimated Percentage of Participants Alive at 5 Years | 86 percentage of patients |
p-value: 0.00995% CI: [1.31, 4.68]Regression, Cox