Five Year Results of Short Course Complete Androgen Blockade With Abiraterone Acetate and LHRH Agonist for Unfavorable Intermediate and Favorable High Risk Prostate Cancer

Abstract

Purpose/Objective(s)Androgen deprivation therapy (ADT) and radiotherapy (RT) are synergistic, and the combination results in improved survival outcomes for aggressive prostate cancers. However, long-term ADT carries substantial burden of toxicity and morbidity. We hypothesized that a combination of definitive prostate RT and short-term complete androgen blockade (CAB) in men with unfavorable intermediate or favorable high-risk localized PC would provide excellent biochemical control and allow high rates of testosterone recovery. This combination would allow an escalation of therapy for unfavorable intermediate risk and de-escalation for favorable high-risk patients. We tested this hypothesis in a prospective trial of neoadjuvant/concurrent/adjuvant abiraterone acetate, prednisone, and LHRH agonist given for 6 months in conjunction with definitive prostate external beam RT. We now report the mature results of this trial.Materials/Methods37 men were enrolled in an IRB-approved NCT-registered prospective multi-center single arm investigator-initiated trial between January 2014 and August 2016. Eligibility required unfavorable intermediate risk of low volume high risk (NCCN) prostate cancer. All men were treated with 6 months of abiraterone acetate (1000mg daily), prednisone (5mg daily), and depot LHRH agonist initiated 8 weeks prior to standard fractionation RT to prostate/seminal vesicles +/- pelvis. Endpoints included PSA and testosterone (T) kinetics, biochemical progression-free survival (PFS), metastasis-free survival (MFS), overall survival (OS), and patient-reported quality-of-life.ResultsEnrolled patients were low volume (T1-2 disease and PSAs < 20 ng/ml), with Grade Group 1 (11%), 2 (11%), 3 (35%), 4 (27%), and 5 (16%); 43% were high-risk. The median follow-up time among all 37 surviving patients is 58months (range 24-65). Treatment was well tolerated and has been reported previously. In the entire cohort, 5-year BPFS was 92% (95% CI 72-98%). 32 out of 37 men recovered T to at least 150 ng/dl; the median time to T recovery was 9.2 mo (95% CI: 9.0-12.2). In men with T recovery, the 5-year BPFS was also 92% (95% CI: 71-98%). Hormonal/sexual function declined at six months but had improved by 24 mo and remained stable thereafter.ConclusionFor select men with aggressive prostate cancer, short course CAB with abiraterone acetate plus prednisone in combination with definitive prostate RT allows rapid T recovery and can provide excellent biochemical control up to 5 years. Short-course CAB is feasible for favorable high risk prostate cancer and may support optimization of patient quality of life. Prospective randomized trials should be considered. Androgen deprivation therapy (ADT) and radiotherapy (RT) are synergistic, and the combination results in improved survival outcomes for aggressive prostate cancers. However, long-term ADT carries substantial burden of toxicity and morbidity. We hypothesized that a combination of definitive prostate RT and short-term complete androgen blockade (CAB) in men with unfavorable intermediate or favorable high-risk localized PC would provide excellent biochemical control and allow high rates of testosterone recovery. This combination would allow an escalation of therapy for unfavorable intermediate risk and de-escalation for favorable high-risk patients. We tested this hypothesis in a prospective trial of neoadjuvant/concurrent/adjuvant abiraterone acetate, prednisone, and LHRH agonist given for 6 months in conjunction with definitive prostate external beam RT. We now report the mature results of this trial. 37 men were enrolled in an IRB-approved NCT-registered prospective multi-center single arm investigator-initiated trial between January 2014 and August 2016. Eligibility required unfavorable intermediate risk of low volume high risk (NCCN) prostate cancer. All men were treated with 6 months of abiraterone acetate (1000mg daily), prednisone (5mg daily), and depot LHRH agonist initiated 8 weeks prior to standard fractionation RT to prostate/seminal vesicles +/- pelvis. Endpoints included PSA and testosterone (T) kinetics, biochemical progression-free survival (PFS), metastasis-free survival (MFS), overall survival (OS), and patient-reported quality-of-life. Enrolled patients were low volume (T1-2 disease and PSAs < 20 ng/ml), with Grade Group 1 (11%), 2 (11%), 3 (35%), 4 (27%), and 5 (16%); 43% were high-risk. The median follow-up time among all 37 surviving patients is 58months (range 24-65). Treatment was well tolerated and has been reported previously. In the entire cohort, 5-year BPFS was 92% (95% CI 72-98%). 32 out of 37 men recovered T to at least 150 ng/dl; the median time to T recovery was 9.2 mo (95% CI: 9.0-12.2). In men with T recovery, the 5-year BPFS was also 92% (95% CI: 71-98%). Hormonal/sexual function declined at six months but had improved by 24 mo and remained stable thereafter. For select men with aggressive prostate cancer, short course CAB with abiraterone acetate plus prednisone in combination with definitive prostate RT allows rapid T recovery and can provide excellent biochemical control up to 5 years. Short-course CAB is feasible for favorable high risk prostate cancer and may support optimization of patient quality of life. Prospective randomized trials should be considered.