Duration of Androgen Deprivation Therapy Influences Outcomes for Patients Receiving Radiation Therapy Following Radical Prostatectomy


      Concurrent/adjuvant androgen deprivation therapy (ADT) is known to improve survival for patients receiving radiation therapy (RT) as a primary treatment for localized prostate cancer. The optimal duration of ADT with RT varies by prostate cancer risk stratification. Short-term (4-6 months) concurrent ADT is considered for those with intermediate-risk disease, and long-term (2-3 years) ADT is recommended for those with high-risk disease. Less in known regarding the optimal duration of ADT in patients who receive either adjuvant or salvage RT (ART or SRT) for a rising prostate-specific antigen (PSA) following radical prostatectomy (RP). We sought to assess if the duration of ADT use influences clinical outcomes for patients receiving RT post-RP.


      Six hundred eighty patients who received ART or SRT at a single institution post-RP were retrospectively reviewed in an IRB approved analysis. We assessed the impact of ADT duration on biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall mortality (OM) using Kaplan-Meier and Cox Proportional Hazards models.


      One hundred forty-four patients (17%) received concurrent/adjuvant ADT with post-RP RT. One hundred thirteen patients received SRT and 31 received ART. No difference existed between the mean duration of ADT in SRT and ART (p = 0.6). Median follow-up post-RT was 57.4 months. Median ADT duration was 12 months (interquartile range [IQR] 6.0-23.7). Patients receiving ADT were dichotomized using median ADT duration. Patients who received <12 months of ADT were at an increased risk for BF (hazard ratio [HR]: 2.3, p = 0.003) and DM (HR: 2.5, p = 0.03) as compared to patients receiving >12 months of ADT. 5-year rates of DM were 6% and 23% for those receiving >12 months, and <12 months of ADT, respectively. On multivariate analysis, when controlling for pre-RT PSA, Gleason score, seminal vesicle invasion, extracapsular extension, presence of positive surgical margins, and the use of ART vs SRT, each month of ADT was associated with a 1.1-fold decrease in risk of BF (p = 0.01), DM (p = 0.01), PCSM (p = 0.04), and OM (p = 0.04). Thus, patients who received 6 months of ADT had a 1.8 fold decrease in risk of BF, DM, PCSM, and OM, whereas patients who received 24 months of ADT had a 9.8-fold decrease in risk of BF, DM, PCSM, and OM.


      For patients receiving concurrent/adjuvant ADT with post-RP RT, the duration of ADT impacts clinical outcomes. Each month of ADT was associated with a statistically significant decrease in BF, DM, PCSM, and OM. Our findings suggest that for patients receiving concurrent/adjuvant ADT with post-RP RT, an extended course of ADT may be preferable. This is consistent with the hypothesis that patients experience BF after post-RP RT because of subclinical metastatic relapse rather than failure of RT to eradicate pelvic disease.


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