AUA 2018: Neoadjuvant Enzalutamide and ADT in High-Risk Prostate Cancer: Initial Imaging and Surgical Findings from a Phase II Clinical Trial

San Francisco, CA ( Samuel Gold along with the lab at the National Cancer Institute sought to investigate the effects of neoadjuvant enzalutamide prior to radical prostatectomy for patients with high-risk prostate cancer in a phase II clinical trial.  Systemic neoadjuvant therapy has been well established in breast and bladder cancers.  Previous studies examining neoadjuvant ADT has demonstrated lower rates of T3 disease and improved cancer-free margin rates.  However, the impact on biochemical recurrence and survival is grossly unknown. Enzalutamide is an androgen receptor antagonist that inhibits receptor translocation and binding to DNA.

In this phase II trial, patients were given 6 months of neoadjuvant enzalutamide and ADT prior to radical prostatectomy.  Multiparametric MRI was performed as a baseline and again after neoadjuvant therapy.  MRI findings were compared to whole mount final pathology.

Twenty patients were included in the study arm and matched to 20 controls.  With similar demographic and disease factors, prostate and tumor volumes decreased in size by 54 and 79% after neoadjuvant therapy, respectively.  Patients treated by neoadjuvant therapy had no upstaged cases to T3/T4 disease as compared to 8/20 patients upstaged in the control arm.  Additionally, almost half of neoadjuvant cases were down-staged to pT2 disease on final pathology. 

Pulse sequences differed in detection abilities.  For initial biopsy lesions, T2 weighted sequence best-depicted presence or absence of the lesion confirmed on pathology.  Diffusion-weighted imaging and dynamic contrast-enhanced series only were strongly positive in 13% and 25% of patients, respectively. 

In conclusion, Samuel states that the long-term success of radical prostatectomy challenged by high-risk prostate cancer patients invites newer neoadjuvant regimens.  Micro- and macroscopic changes induced by enzalutamide and ADT alter mpMRI imaging of prostate cancer with the pulse sequences depicting lesions with varied effectiveness.  This clinical trial suggests the need for a phase III trial, as select patients may benefit from neoadjuvant systemic therapy with some of these newly developed agents. 

Presented by: Samuel Gold, BA, Urologic Oncology Branch, National Cancer Institute
Co-Authors: Sahwn Marhamati, Bethesda, MD, Stephanie Harmon, Frederick, MD, Jonathan Bloom, Fatima Karzai, Graham Hale, Kareem Rayn, Vik Sabarwal, Sherif Mehralivand, Marcin Czarniecki, Clayton Smith, David VanderWeele, William Dahut, Baris Turkbey, Peter Pinto, Bethesda, MD

Written by:  David B. Cahn, DO, MBS Fox Chase Cancer Center Philadelphia, PA @dbcahn at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA