Abiraterone, Androgen Deprivation Therapy, and Radiotherapy for Localized Intermediate/High Risk Prostate Cancer: Long-Term Follow-Up of the RAD1 Phase 2 Trial

Abstract

<h3>Purpose/Objective(s)</h3> Radiotherapy (RT) combined with androgen-deprivation therapy (ADT) is an established standard of care for high-risk non-metastatic prostate cancer (PCa). Ongoing studies are evaluating whether treatment intensification of systemic therapy can improve outcomes. Recent data from a STAMPEDE meta-analysis showed improvement in metastasis-free survival with addition of abiraterone. In 2015, we reported the first study combining neoadjuvant and concurrent abiraterone with LHRH agonist in patients undergoing primary RT for localized PCa. We present long-term follow up of this small phase II trial. <h3>Materials/Methods</h3> Patients with intermediate (Gleason 7 or PSA 10-20), high risk (cT3/T4, Gleason 8-10 or PSA >20) or node positive PCa were enrolled on a single-arm phase 2 IRB-approved study. Study therapy consisted of 24 weeks of LHRH agonist (without anti-androgen) combined with abiraterone (1000mg daily), and prednisone. After 12 weeks of neoadjuvant therapy, patients underwent conventional dose-escalated intensity modulated radiotherapy (IMRT). Duration of adjuvant ADT was per treating physician discretion, generally 6 months for intermediate and 24 months for high-risk disease. Primary endpoint was to determine the safety of concurrent abiraterone with RT (previously reported). Event outcomes (secondary endpoints) were calculated from start of study therapy to biochemical recurrence (BCR, Phoenix definition), distant metastasis (DM), death from any cause, and death from prostate cancer. Survival analyses were calculated using Kaplan-Meier (KM) method. <h3>Results</h3> From 2011-2013, 22 patients with high risk (n=19) or intermediate risk (n=3) PCa were enrolled, negative for distant metastatic disease by bone scan and CT. Patient details included age (median 62, range 43-81), T classification (T1c/T2, n=15; T3, n=7), Gleason sum (7, n=10; 8-10, n=12), PSA (median 20, range 4.8-155). Three were node positive, and 8 had high risk criteria meeting eligibility for the recent STAMPEDE trials (node positive or at least two criteria: T3/T4, Gleason 8–10, and PSA ≥40). 2 patients withdrew before completing study therapy and were excluded from analyses. Median RT dose was 81 Gy; all but 1 patient received pelvic nodal RT (median dose 50.4 Gy). Median PSA nadir was 0 (range <0.03-0.2). At median follow up of 109 months (IQR 96-115), 3 patients have died (1 of PCa, 2 other causes), 3 had BCR, and 3 had DMs. KM 8-year BCR-free survival was 81%, DM-free survival 78%, overall survival 84%, prostate cancer-specific survival 94%. <h3>Conclusion</h3> In this small cohort of patients with intermediate/high risk prostate cancer, combination therapy with abiraterone, ADT and RT were well-tolerated and associated with excellent long-term disease control outcomes. Our findings are in line with recent STAMPEDE analyses in this patient population supporting intensification of therapy with abiraterone. Further larger studies are warranted to refine patient selection for this approach.