Neoadjuvant Enzalutamide Prior to Prostatectomy.

Area of Science:

• Oncology
• Urology
• Pharmacology

Background:

• Prostate cancer growth is driven by androgen receptor (AR) activation.
• Effective AR antagonism is crucial for managing localized and metastatic prostate cancer.
• Neoadjuvant therapy aims to reduce tumor burden before surgery.

Purpose of the Study:

• To evaluate neoadjuvant therapy with enzalutamide (AR antagonist) alone or combined with dutasteride and leuprolide (LHRHa) before prostatectomy.
• To assess the efficacy of these regimens in achieving pathologic complete response (pCR) and minimal residual disease (MRD).
• To analyze residual cancer burden (RCB) and androgen levels in relation to treatment response.

Main Methods:

• A total of 48 men with localized prostate cancer received 6 months of neoadjuvant therapy.
• Treatment arms included enzalutamide alone or enzalutamide/dutasteride/LHRHa.
• Outcomes measured were pCR, MRD, RCB, PSA, and tissue/serum androgen concentrations.

Main Results:

• The enzalutamide arm showed no pCR or MRD.
• The enza/dut/LHRHa arm achieved a 4.3% pCR and 13.0% MRD rate.
• Median RCB was significantly lower with combination therapy (0.06 cm³ vs. 0.41 cm³).

Conclusions:

• Combination therapy (enza/dut/LHRHa) yielded pCR and MRD rates similar to historical controls.
• Continued AR activity in residual tumors suggests a role in cancer cell survival.
• More potent AR signaling inhibition strategies are required for greater antitumor efficacy.