Platelets, Chromogranin A, and C-Reactive Protein Predict Therapy Failure of Metastatic Hormone-Sensitive Prostate Cancer while miR-375 Outperforms Prostate-Specific Antigen in Stratifying Castration-Resistant Prostate Cancer

Androgen deprivation therapy has long been the first-line treatment for hormone-sensitive prostate cancer (HSPC). After progression to castration-resistant prostate cancer (CRPC), androgen receptor pathway inhibitors (ARPIs) are commonly used. Recently, combined therapy with androgen deprivation and an ARPI has been recommended for metastatic HSPC patients. Novel markers are urgently needed for monitoring this disease and for making therapeutic decisions. Plasma samples were collected from 140 patients with either metastatic HSPC (n = 72) or CRPC (n = 68) before the start of ARPI therapy. Digital PCR was used to assess AR gene amplification, while the expression levels of miR-375 were measured by quantitative PCR. Sixteen other clinical markers were also evaluated, including prostate-specific antigen (PSA), chromogranin A (CGA), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), C-reactive protein (CRP), lymphocyte-to-monocyte ratio, and platelet count. A multivariate analysis, adjusted for age and metastatic dissemination, identified miR-375 expression and lymphocyte-to-monocyte ratio to be the independent negative predictors of ARPI therapy failure in CRPC patients. Regarding the HSPC patients, this article reports the primary finding of the independent negative predictive value of platelet count, CRP, and CGA for the failure of combined androgen deprivation therapy and ARPI.