Castration-resistant prostate cancer monitoring by cell-free circulating biomarkers.

Background: Prostate cancer is the second leading cause of male cancer-related deaths in Western countries, which is predominantly attributed to the metastatic castration-resistant stage of the disease (CRPC). There is an urgent need for better prognostic and predictive biomarkers, particularly for androgen receptor targeted agents and taxanes.

Methods: We have searched the PubMed database for original articles and meta-analyses providing information on blood-based markers for castration-resistant prostate cancer monitoring, risk group stratification and prediction of therapy response.

Results: The molecular markers are discussed along with the standard clinical parameters, such as prostate specific antigen, lactate dehydrogenase or C-reactive protein. Androgen receptor (AR) alterations are commonly associated with progression to CRPC. These include amplification of AR and its enhancer, point mutations and splice variants. Among DNA methylations, a novel 5-hydroxymethylcytosine activation marker of TOP2A and EZH2 has been identified for the aggressive disease. miR-375 is currently the most promising candidate among non-coding RNAs and sphingolipid analysis has recently emerged as a novel approach.

Conclusions: The promising biomarkers have the potential to improve the care of metastatic prostate cancer patients, however, they need further validation for routine implementation.