Castration-Synchronized Upfront Docetaxel for metastatic Hormone Sensitive Prostate Cancer considering Epithelial to Mesenchymal Transition

Abstract

Upfront docetaxel therapy for metastatic hormone sensitive prostate cancer (mHSPC) has been reported to be improved outcome, although the best timing to start decetaxel and/or the duration of chemotherapy have not been cleared. We consider epithelial to mesenchymal transition (EMT) at the beginning of the hormonal therapy would be the mechanism to obtain apoptosis tolerance of prostatic cells. For localized prostate cancer, we used LH-RH antagonist (degarelix) twice and performed high-intensity focused ultrasound therapy (HIFU) after two weeks of the first degarelix, the timing of inducing EMT. This regimen apparently improved HIFU results. So for mHSPC, we started two to three courses of upfront docetaxel synchronously the beginning of the androgen deprivation therapy (ADT). Of 38 mHSPC patients underwent upfront docetaxel with our protocol, 18 patients maintained low prostate specific antigen value less than 0.1 ng/ml for more than two years without adding new androgen axis targeted therapy agents (ARAT). Although recent study suggests all mHSPC patients should receive systemic triple therapy including ADT, docetaxel and ARAT, our study indicated that upfront docetaxel use considering EMT may select the patients requiring triple therapy, and reduce a burden both for the patients and medical economy.