Neoadjuvant enzalutamide and androgen deprivation therapy for high-risk prostate cancer: Early results from a feasibility trial.

Abstract

94 Background: Intensive androgen-targeted therapy improves survival for patients with androgen naive metastatic prostate cancer. Neoadjuvant androgen deprivation therapy (nADT) with abiraterone for localized disease leads to complete responses (pCR) rates of up to 10%. In this study we tested the efficacy of nADT with enzalutamide for patients with high risk, localized disease and the ability of post-treatment multiparametric MRI (mpMRI) to evaluate response. Methods: A single institution trial (NCT02430480) evaluated nADT and enzalutamide 160 mg daily in patients with high risk non-metastatic prostate cancer. Patients underwent MRI-TRUS-guided fusion biopsy at screening and repeat mpMRI followed by radical prostatectomy (RP) after completing six months of therapy. Results: Twenty patients have completed therapy and undergone radical prostatectomy. Clinical characteristics were typical of those with high risk disease: median PSA 8.96 ng/ml (range 2.07-985.9) and clinical stage by mpMRI cT2 (one patient), cT3 (17 patients), or cT4 (2 patients); 7 patients had enlarged pelvic lymph nodes. Following 6 months of therapy, median pre-RP PSA was < 0.02 ng/ml (range < 0.02 – 0.35). On final pathology, 0 patients were upstaged, 5 (25%) were unchanged, and 15 (75%) were downstaged, including 3 (16%) pCR. Four patients were downstaged from N1 to N0. There was little correlation between post-treatment mpMRI tumor volume and pathologic tumor volume. Two patients had radiographic complete responses, one of whom had extensive residual disease. Conclusions: Six months of nADT with enzalutamide has activity in high risk, localized prostate cancer, with a small number of patients having exceptional responses. Standard analysis of mpMRI does not reliably characterize depth of response. Evaluation of molecular characteristics that predict exceptional response or intrinsic resistance is on-going. Patients are being followed for recurrence. Clinical trial information: NCT02430480.