Abstract 618: The morphologic effects of treatment with neoadjuvant enzalutamide and androgen deprivation therapy in high risk prostatic cancer: What the pathologist needs to know
Authors: Merino Maria J. , Dikoglu Esra , Pinto Peter , Turkbey Baris , Dahut William , Chun Guinevere , Madan Ravi A. , Karzai Fatima 
Published: September 2020

Abstract
Background: In this study we report the effects of neoadjuvant enzalutamide (enza) plus androgen deprivation therapy (ADT) in the prostatectomy specimens of patients receiving this therapy, and the immunoprofile of the tumors. Prostate cancer is the most common cancer in men, affecting 1 out of 9 men in the US. Treatment for newly diagnosed, non-metastatic, high-risk disease includes surgery or radiation in combination with ADT. Enza, an androgen receptor antagonist, is FDA approved for non-metastatic and metastatic castrate-resistant prostate cancer. Studies have shown intensive androgen receptor targeting for localized disease can lead to complete responses.
Design: Single institution study (NCT02430480) evaluating 6 months of neoadjuvant enza (160 mg daily) plus ADT in patients with high risk non-metastatic prostatic cancer. Twenty-two prostatectomy specimens were evaluated. Specimens were fixed in formalin and paraffin embedded following the protocol established for these specimens. Detailed morphological evaluation was performed and tumors compared with prior diagnostic biopsies. Correlation with prior multiparametric MRI (mpMRI) was done. Sections with tumor were obtained (4mm thickness) and stained for IHC for PTEN antibody (Cell signaling), AR (Abcam) and ERG (Abcam)
Results: Patients ranged in age from 43 to 73 years (med 61years). Prior biopsies included Gleason scores of 7(3+4,5 cases); 7(4+3, 3 cases), 8(4+4, 5 cases),9(4+5, 8 cases), 10(1 case). Grossly, the prostatectomy specimens appeared smaller in size. Reviewing prior mpMRI, it was noted that the median prostate volume decreased by 50.7% after 6 months of treatment. No tumor was identified in 2 cases; one with multiple Gleason grade 8 biopsies and the other one Gleason grade 9 in all prior biopsies. In all except 2 cases, the most striking histologic change was the tumor cells that often resembled fusiform histiocytes growing in discrete clusters or individual cells. Occasional small gland formation was present in some cases. Prominent basal cell hyperplasia was present as well as nodular stromal hyperplasia that in MRI mimic cancer. The amount of tumor present varied from bilateral involvement to 10% of one lobe. Most cases were stage pT2 and pT3. 20 cases were positive for AR, 3 had loss of PTEN and 5 had ERG expression (total 22 cases).
Conclusions: Enzalutamide is a potent antiandrogen with promising results in the neoadjuvant treatment of high-risk prostatic cancer. We report in this study the effect and morphologic changes that occur in the tumor as the result of this therapy. Recognition of these morphologic changes is important since the residual tumor may appear different than the prior diagnostic biopsies.
Citation Format: Maria J. Merino, Esra Dikoglu, Peter Pinto, Baris Turkbey, William Dahut, Guinevere Chun, Ravi A. Madan, Fatima Karzai. The morphologic effects of treatment with neoadjuvant enzalutamide and androgen deprivation therapy in high risk prostatic cancer: What the pathologist needs to know [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 618.