**The Importance of Time to Prostate-Specific Antigen (PSA) Nadir after Primary Androgen Deprivation Therapy in Hormone-Naïve Prostate Cancer Patients**

### **Takeshi Sasaki and Yoshiki Sugimura \***

Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan; t-sasaki@clin.medic.mie-u.ac.jp

**\*** Correspondence: sugimura@clin.medic.mie-u.ac.jp; Tel.: +81-59-232-1111

Received: 26 November 2018; Accepted: 18 December 2018; Published: 18 December 2018

**Abstract:** Prostate-specific antigen (PSA) is currently the most useful biomarker for detection of prostate cancer (PCa). The ability to measure serum PSA levels has affected all aspects of PCa managemen<sup>t</sup> over the past two decades. The standard initial systemic therapy for advanced PCa is androgen-deprivation therapy (ADT). Although PCa patients with metastatic disease initially respond well to ADT, they often progress to castration-resistant prostate cancer (CRPC), which has a high mortality rate. We have demonstrated that time to PSA nadir (TTN) after primary ADT is an important early predictor of overall survival and progression-free survival for advanced PCa patients. In in vivo experiments, we demonstrated that the presence of fibroblasts in the PCa tumor microenvironment can prolong the period for serum PSA decline after ADT, and enhance the efficacy of ADT. Clarification of the mechanisms that affect TTN after ADT could be useful to guide selection of optimal PCa treatment strategies. In this review, we discuss recent in vitro and in vivo findings concerning the involvement of stromal–epithelial interactions in the biological mechanism of TTN after ADT to support the novel concept of "tumor regulating fibroblasts".

**Keywords:** prostate-specific antigen; androgen deprivation therapy; time to PSA nadir; fibroblasts
