**6. Concluding Remarks**

TTN after primary ADT for advanced PCa patients is a powerful tool for predicting disease progression and overall survival. Clarification of the mechanisms associated with TTN after primary ADT could help inform treatment decision-making to determine optimal strategies for PCa treatment. In this review, we focused on stromal–epithelial interactions to develop a clearer picture of the biological mechanism of TTN after ADT, based on findings from in vitro and in vivo experiments to provide a novel concept of "tumor regulating fibroblasts".

**Author Contributions:** T.S. wrote the first draft of the manuscript; Y.S. revised the manuscript and added additional text.

**Funding:** This work was funded by Grants-in Aid from the Ministry of Education for Science and Culture of Japan (Grant No. 26861266, 18K16690 to T.S.).

**Acknowledgments:** We are grateful to Kenichiro Ishii of the Department of Oncologic Pathology, Mie University Graduate School of Medicine, for valuable discussions.

**Conflicts of Interest:** The authors declare no conflict of interest.
