Targeting backdoor androgen synthesis through AKR1C3 inhibition: A presurgical hormonal ablative neoadjuvant trial in high-risk localized prostate cancer.

Background: Localized prostate cancers (PCs) may resist neoadjuvant androgen receptor (AR)-targeted therapies as a result of persistent intraprostatic androgens arising through upregulation of steroidogenic enzymes. Therefore, we sought to evaluate clinical effects of neoadjuvant indomethacin (Indo), which inhibits the steroidogenic enzyme AKR1C3, in addition to combinatorial anti-androgen blockade, in men with high-risk PC undergoing radical prostatectomy (RP).

Methods: This was an open label, single-site, Phase II neoadjuvant trial in men with high to very-high-risk PC, as defined by NCCN criteria.