Prostate cancer is the most common malignancy in males and, despite a marked improvement
in diagnostic techniques, a not small percentage of prostate tumours is still diagnosed in
advanced stage. It is now clear that prostate cancer passes through distinct phases during its natural
history, starting from an initial phase, in which the disease has a locoregional extent, until a very late
phase when it becomes refractory to hormone therapy.
It is important to distinguish between local disease, in which tumor may be considered localized in
the gland and a systemic disease characterized by high tumor burden and/or dissemination of circulating
All the prostate cancers, at first diagnosis, are characterized by high sensitivity to the androgen deprivation
therapy (ADT); however, during the natural history, after a variable period, they become
castration resistant. In the past, few therapy options were available for castration resistant prostate
cancer, while at present much more approaches can be employed, both hormone-based therapies and
chemotherapy regimens. Hypercastration agents are defined as drugs capable to target the androgenandrogen
receptor axis even in castrate resistant conditions. Abiraterone and enzalutamide are the
only two hypercastration agents available for clinical use.
Osteoclast targeted agents, such as zoledronic acid and denosumab can always been employed, but
their use should be limited to the castrate resistant setting.
The optimal understanding of all phases characterizing the natural history of prostate cancer may
certainly be useful for the selection of the best therapeutic options in prostate cancer.