2302: Greater Than 6 Months of Androgen Deprivation Therapy Does Not Improve Overall Survival for High-Risk Prostate Cancer Patients Treated With Radiotherapy or Prostatectomy

Abstract

To analyze the effect of the duration of androgen deprivation (AD) in the definitive treatment of high-risk prostate cancer. A total of 579 patients with high-risk prostate cancer were treated definitively at the Cleveland Clinic from 1998 to 2003 with either external beam radiation (RT, n=390), radical prostatectomy (RP, n=165), or permanent prostate implant (PI, n=24). High-risk disease was defined as: initial PSA (iPSA)> 20, Gleason score (GS) 8–10, clinical stage T3, or iPSA 10–20 and GS 7. The study endpoints were: biochemical failure [(bF), using the ASTRO consensus definition for RT and PI patients and two consecutive PSA’s ≥0.2ng/ml for RP patients], clinical failure [(cF), defined as the detection of biopsy proven local recurrence, or evidence of definite metastases to bone, lymph nodes, or elsewhere] and overall survival (OS). Cox proportional hazards regression was used to determine what factors, including iPSA, GS, stage, AD, age, race, income, BMI, and smoking history correlated with bF, cF, and OS. Median follow up was 60 months (range: 24–114). Median age for all patients was 67 years (range: 41–85). AD was given to 426 (73.6%) patients, with 82.6% of those patients receiving 1–6 months (median 6 months) and 17.4% receiving >6 months (median 15 months) of AD. Univariate analysis revealed that > 6 months of AD had no statistically significant impact on bF or cF, but did result in a statistically significant worse OS, (p=0.0003). Other factors found to result in worse OS on univariate analysis included GS ≥ 8 (p=0.0424), active tobacco use (p=0.0467), and increasing number of pack-years smoked (p=0.0139). Kaplan-Meier estimates of OS for patients receiving no AD vs. 1–6 months of AD vs. > 6 months of AD were 92%, 92%, and 76% at 5-years and 78%, 84%, and 67% at 7-years, respectively (p=0.0007). The use of >6 months of AD remained an independent predictor of death on multivariate analysis (RR 2.158, p=0.0329), as did Gleason score and increasing number of pack-years smoked. While smoking and use of >6 months of AD both had a detrimental effect on OS, no synergistic effect between the two factors was detected. In high-risk patients treated with radiotherapy or prostatectomy, longer duration of androgen deprivation (> 6 months) does not improve biochemical or clinical failure rates, and appears to result in worse overall survival. The cause of this lower overall survival is unknown and warrants further investigation.