Single-arm phase 2 clinical trial evaluating neoadjuvant abiraterone and gonadotrophin-releasing hormone agonist in high-risk localised prostate carcinoma: CTRIAL-IE (ICORG) 13-23.
Authors: Murphy Geraldine , Parker Imelda , Sheehan Martina , Kelly Paul J. , Small Cormac , Thirion Pierre Guillame 
Published: March 2023

360 Background: Our aim was to evaluate the clinical, radiological and biochemical response achieved by 4 months of neo-adjuvant (NA) combination hormone therapy (HT) comprising abiraterone acetate (AA), prednisolone and gonadotrophin-releasing hormone (GnRH) agonist in treatment-naïve high-risk localised prostate carcinoma (HRLPC) prior to radical radiotherapy (RRT). Methods: This single-arm phase II clinical trial recruited 45 patients between 07/15 and 02/2020. Patients presenting with RTOG HRLPC, planned for RRT combined with short or long-term HT, were eligible. Patients completed 4 months of NA combined AA and GnRH agonist. The primary outcomes assessed at 4 months were 1) the mean percentage reduction at 99 days in prostate gland volume (PGV) via transrectal ultrasound, 2) the change in PSA levels, and 3) the percentage of patients achieving a complete clinical and biochemical response as defined by normalisation of DRE and PSA <0.1ng/ml. The secondary endpoints included the decrease in testosterone level, PSA kinetics and change in urinary symptoms. Adverse events (AE) in the form of HT-related symptoms and sexual function were also assessed. Results: The mean percentage reduction in PGV from baseline at day 99 was 42.4 % [CI 38.6-46.2]. Of 11 patients, who may have been deemed unsuitable for brachytherapy due to large PGV (>50cm3) at initial assessment, 9 patients achieved PGV reduction. The median reduction in PSA from baseline at 4 months was 13.7 ng/mL (3 – 146). A total of 33 patients (80.5%) achieved a PSA value of <0.1ng/ml at day 126. The median reduction from baseline reached 13.6ng/mL (range 3-144) at day 43 and remained unchanged up to 2 months post radiotherapy. A total of 16 patients (48.5% of 33 patients with day 126 assessment) had a complete clinical and biochemical response. By day 43, every patient had a testosterone level of <0.5nmol/L. The median International Prostate Symptom Score at baseline was 9 (range 0-32). The median change from baseline at day 126 was -1 (range -30-10), indicating minimal improvement. 95.6% of patients experienced an AE related to AA. There was no grade 4 or grade 5 AE. A total of 18 patients (40%) experienced, the most common of which was hypertension or elevated liver enzymes. 5 patients (11.1%) discontinued AA secondary to AE. The percentage of patients with normal erectile function and normal intercourse satisfaction decreased from 44.4% and 46.7% respectively at baseline to 2.3% by day 126. The percentage of patients with normal overall satisfaction decreased from 72.5% at baseline to 50% at day 126. Conclusions: NA HT with AA and GnRH agonist achieved a very high rate of undetectable PSA for HRLPC and substantial PGV reduction which may lead to improved eligibility for brachytherapy. Sexual function and satisfaction were significantly impacted. Clinical trial information: NCT02160353 .