Androgen Deprivation Therapy in Patients Treated with External Beam Radiotherapy for High-risk Prostate Cancer in the PSA Era

Abstract

Purpose/Objective(s)To assess the effect of long-term androgen deprivation (AD) therapy in patients with high-risk prostate cancer treated with high-dose external beam radiotherapy (EBRT) in the PSA era.Materials/MethodsPatients treated using EBRT with ≥78 Gy biologic equivalent dose for high-risk prostate cancer from 1996–2007 were studied. High-risk was defined as pretreatment PSA (iPSA) >20 ng/mL, biopsy Gleason score (bGS) 8–10, clinical-stage T3, or having two intermediate risk factors: clinical-stage T2b or T2c, bGS 7, or iPSA 10–20 ng/mL. All patients had at least two post-treatment PSA tests. Multivariate analysis (MVA) with Cox proportional hazards regression was used to examine variables which may affect biochemical recurrence-free survival (bRFS), clinical recurrence-free survival (cRFS), and overall survival (OS): Charlson score; age; race; BMI; iPSA; bGS; clinical-stage; use, and duration (0 vs. 1–6 months vs. >6 months) of AD. The bRFS rates were calculated using the nadir+2 definition of biochemical failure (bF). Clinical failure (cF) included local and/or distant disease recurrence. A descriptive analysis of development of hormone refractory prostate cancer was performed for patients treated with salvage AD.ResultsA total of 553 high-risk patients with a median follow-up of 75 months were studied. Thirty-six (6.5%) patients received no AD, 403 (72.9%) received 1–6 months of AD, and 114 (20.6%) received >6 months of AD. For the entire group, 5-year bRFS was 73.6%, cRFS was 85.6%, and OS was 86.5%. The 5-year bRFS rate for patients treated with no AD was 86.2%, 72.8% for 1–6 months AD, and 72.0% for >6 months AD. The 5-year cRFS rate for patients treated with no AD was 100%, 85.3% for 1–6 months AD, and 84.3% for >6 months AD. The 5-year OS rate for patients treated with no AD was 89.8%, 87.8% for 1–6 months AD, and 79.5% for >6 months AD. On MVA, after controlling for bGS, stage, and iPSA, use of >6 months AD did not result in improved bRFS (p = 0.4200) or cRFS (p = 0.3451) and was associated with worse OS compared to 1–6 months (p = 0.0128). One hundred twenty-four patients received salvage therapy after bF or cF, and 40.3% of these patients subsequently developed HRPC. The HRPC occurred sooner for patients treated with >6 months upfront AD (median 47 months), compared to patients treated without upfront AD (median 100 months) or 1–6 months upfront AD (median 741 months).ConclusionsGreater than 6 months of AD does not appear to benefit patients with high-risk prostate cancer treated with high-dose EBRT in the PSA era. Purpose/Objective(s)To assess the effect of long-term androgen deprivation (AD) therapy in patients with high-risk prostate cancer treated with high-dose external beam radiotherapy (EBRT) in the PSA era. To assess the effect of long-term androgen deprivation (AD) therapy in patients with high-risk prostate cancer treated with high-dose external beam radiotherapy (EBRT) in the PSA era. Materials/MethodsPatients treated using EBRT with ≥78 Gy biologic equivalent dose for high-risk prostate cancer from 1996–2007 were studied. High-risk was defined as pretreatment PSA (iPSA) >20 ng/mL, biopsy Gleason score (bGS) 8–10, clinical-stage T3, or having two intermediate risk factors: clinical-stage T2b or T2c, bGS 7, or iPSA 10–20 ng/mL. All patients had at least two post-treatment PSA tests. Multivariate analysis (MVA) with Cox proportional hazards regression was used to examine variables which may affect biochemical recurrence-free survival (bRFS), clinical recurrence-free survival (cRFS), and overall survival (OS): Charlson score; age; race; BMI; iPSA; bGS; clinical-stage; use, and duration (0 vs. 1–6 months vs. >6 months) of AD. The bRFS rates were calculated using the nadir+2 definition of biochemical failure (bF). Clinical failure (cF) included local and/or distant disease recurrence. A descriptive analysis of development of hormone refractory prostate cancer was performed for patients treated with salvage AD. Patients treated using EBRT with ≥78 Gy biologic equivalent dose for high-risk prostate cancer from 1996–2007 were studied. High-risk was defined as pretreatment PSA (iPSA) >20 ng/mL, biopsy Gleason score (bGS) 8–10, clinical-stage T3, or having two intermediate risk factors: clinical-stage T2b or T2c, bGS 7, or iPSA 10–20 ng/mL. All patients had at least two post-treatment PSA tests. Multivariate analysis (MVA) with Cox proportional hazards regression was used to examine variables which may affect biochemical recurrence-free survival (bRFS), clinical recurrence-free survival (cRFS), and overall survival (OS): Charlson score; age; race; BMI; iPSA; bGS; clinical-stage; use, and duration (0 vs. 1–6 months vs. >6 months) of AD. The bRFS rates were calculated using the nadir+2 definition of biochemical failure (bF). Clinical failure (cF) included local and/or distant disease recurrence. A descriptive analysis of development of hormone refractory prostate cancer was performed for patients treated with salvage AD. ResultsA total of 553 high-risk patients with a median follow-up of 75 months were studied. Thirty-six (6.5%) patients received no AD, 403 (72.9%) received 1–6 months of AD, and 114 (20.6%) received >6 months of AD. For the entire group, 5-year bRFS was 73.6%, cRFS was 85.6%, and OS was 86.5%. The 5-year bRFS rate for patients treated with no AD was 86.2%, 72.8% for 1–6 months AD, and 72.0% for >6 months AD. The 5-year cRFS rate for patients treated with no AD was 100%, 85.3% for 1–6 months AD, and 84.3% for >6 months AD. The 5-year OS rate for patients treated with no AD was 89.8%, 87.8% for 1–6 months AD, and 79.5% for >6 months AD. On MVA, after controlling for bGS, stage, and iPSA, use of >6 months AD did not result in improved bRFS (p = 0.4200) or cRFS (p = 0.3451) and was associated with worse OS compared to 1–6 months (p = 0.0128). One hundred twenty-four patients received salvage therapy after bF or cF, and 40.3% of these patients subsequently developed HRPC. The HRPC occurred sooner for patients treated with >6 months upfront AD (median 47 months), compared to patients treated without upfront AD (median 100 months) or 1–6 months upfront AD (median 741 months). A total of 553 high-risk patients with a median follow-up of 75 months were studied. Thirty-six (6.5%) patients received no AD, 403 (72.9%) received 1–6 months of AD, and 114 (20.6%) received >6 months of AD. For the entire group, 5-year bRFS was 73.6%, cRFS was 85.6%, and OS was 86.5%. The 5-year bRFS rate for patients treated with no AD was 86.2%, 72.8% for 1–6 months AD, and 72.0% for >6 months AD. The 5-year cRFS rate for patients treated with no AD was 100%, 85.3% for 1–6 months AD, and 84.3% for >6 months AD. The 5-year OS rate for patients treated with no AD was 89.8%, 87.8% for 1–6 months AD, and 79.5% for >6 months AD. On MVA, after controlling for bGS, stage, and iPSA, use of >6 months AD did not result in improved bRFS (p = 0.4200) or cRFS (p = 0.3451) and was associated with worse OS compared to 1–6 months (p = 0.0128). One hundred twenty-four patients received salvage therapy after bF or cF, and 40.3% of these patients subsequently developed HRPC. The HRPC occurred sooner for patients treated with >6 months upfront AD (median 47 months), compared to patients treated without upfront AD (median 100 months) or 1–6 months upfront AD (median 741 months). ConclusionsGreater than 6 months of AD does not appear to benefit patients with high-risk prostate cancer treated with high-dose EBRT in the PSA era. Greater than 6 months of AD does not appear to benefit patients with high-risk prostate cancer treated with high-dose EBRT in the PSA era.