Person:

Yang, David

Background While the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) is known to improve overall survival for patients with high-risk prostate cancer (Gleason score of 8-10, prostate-specific antigen [PSA] >20 ng/mL, or cT3-T4 stage), it is unclear whether the benefit of ADT differs by the Gleason score, PSA level, and use of a brachytherapy boost. Additionally, it is unknown whether there is an association between the use of ADT and development of anxiety and rheumatoid arthritis (RA). We examined [1] the association between ADT and overall survival for patients with high-risk prostate cancer, with stratification by the PSA level, Gleason score, and use of a brachytherapy boost, and [2] the association between use of ADT and development of anxiety and RA.

Methods To study the efficacy of ADT, we identified three retrospective cohorts of approximately 20,000-50,000 men each from the National Cancer Database diagnosed from 2004-2011 with high-risk prostate cancer and treated with EBRT. To examine the side-effects of ADT, we identified two retrospective cohorts of approximately 70,000 and 100,000 men from the Surveillance, Epidemiology, and End Results-Medicare database diagnosed with stage I-III prostate cancer from 1992-2006. We utilized Cox proportional hazards regression to examine the association between use of ADT and [1] overall survival and [2] diagnosis of anxiety and RA.

Results First, of patients with Gleason 8-10 treated with EBRT, ADT was associated with a significant improvement in overall survival for patients with PSA >2.5 ng/mL (adjusted hazard ratio [AHR] 0.87, 95% confidence interval [CI] 0.81-0.94, P<0.001) but not for PSA ≤2.5ng/mL (AHR 1.36, 95% CI 0.96-1.94, P=0.084; Pinteraction=0.021). Second, among Gleason 8-10 patients treated with EBRT, ADT was associated with a significant improvement in overall survival for Gleason 8 disease (AHR 0.78, 95% CI 0.70-0.87, P<0.001) but not Gleason 9-10 disease (AHR 0.96, 95% CI 0.84-1.11, P=0.625; Pinteraction=0.020). A higher Gleason score (8, 9, 10) correlated with a lesser overall survival benefit from ADT (Pinteraction=0.012). Third, ADT was associated with a significant improvement in overall survival for high-risk patients who received EBRT only (AHR 0.91, 95% CI 0.86-0.96, P=0.001) but not for patients who also received a brachytherapy boost (AHR 1.05, 95% CI 0.91-1.21, P=0.496; Pinteraction=0.036). Fourth, patients who received ADT had an 8% increased risk of developing anxiety (P=0.054), and a longer duration of ADT was associated with a higher risk of new-onset anxiety (Ptrend=0.012). Lastly, patients who received ADT had a 23% higher risk of developing RA (P=0.001), and a longer duration of ADT was associated with a higher risk of developing RA (Ptrend<0.001).

Conclusions Using large, retrospective cohorts of patients with high-risk prostate cancer, we found that the overall survival advantage of ADT differs by the PSA level, Gleason score, and use of a brachytherapy boost. Additionally, we identified associations between receipt of ADT and development of anxiety and RA. The results of this study will help guide the personalization of therapy for patients with prostate cancer by identifying patients who may not experience a significant benefit from ADT and require treatment intensification using novel, targeted agents, as well as providing more information on the adverse effects of ADT.