Recent developments in the treatment of non-metastatic castration resistant prostate cancer

Non-metastatic castration resistant prostate cancer (nmCRPC) is defined as a disease state withlack of radiographic evidence of metastatic disease, a confirmed rising PSA level on continuous ADT and maintaining a castrate level of testosterone following definitive therapy. Prior to the publication of PROSPER, SPARTAN and ARAMIS, no trials have demonstrated a clinical benefit for these patients. Recently enzalutamide, apalutamide, and darolutamide respectively, were tested in this disease setting with metastasis free survival (MFS) as the primary endpoint for each trial. In this review article, we define key terms related to the discussion of nmCRPC, examine the clinical trial design, and safety profile for each of these three key clinical trials and present updated overall survival (OS) results from these studies. Also we specifically discuss the key clinical trial results including the primary endpoint of MFS for each trial as well as quality of life effects of these three androgen receptor antagonists. Finally, this article examines the potential impact of molecular imaging testing on the applicability of these clinical trial results.