Non-metastatic CRPC and asymptomatic metastatic CRPC: which treatment for which patient?

The introduction of early PSa-based diagnosis has profoundly impacted the epidemiology of castration-resistant prostate cancer (CRPC). Many patients enter the disease at an early stage when the only sign of resistance to androgen deprivation therapy (ADT) is a progressive elevation of prostate-specific antigen (PSA). This created a very heterogeneous population of non-metastatic (M0) CRPC. PSa kinetics is the most powerful indicator of aggressiveness in that population and can be used to trigger imaging investigation and enrollment in clinical trials. Several registered and near to come treatments have not been tested in that population but in men with more advanced metastatic and often symptomatic disease. Several agents have been investigated to delay the onset of the first bone metastasis but only one, denosumab, has reached its end-point. Because CRPC remains largely driven by the androgen receptor (AR), physicians have relied on second-line hormonal manipulations to delay the progression of the disease, including first generation antiandrogens, adrenal synthesis inhibitors, steroids and estrogens. The data however are mostly limited to phase II trials.