الفهرس 
Anatomy of the ProstateOnly 14 pages are availabe for public view
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Abstract
Summary and conclusion
Castrate-resistant prostate cancer (CRPC) is defined by disease progression despite androgen depletion therapy (ADT) with castrate serum level of testosterone and may present as either a continuous rise in serum prostate-specific antigen (PSA) levels, the progression of pre-existing disease, and/or the appearance of new metastases, PSA-based diagnosis has profoundly impacted the epidemiology of castration-resistant prostate cancer ”CRPC”.
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” despite castrate testosterone level
CRPC is diagnosed by one or more of the following:
• Castrate serum testosterone < 50 ng/ml or 1.7 nmol/L
• Either: Biochemical progression: Three consecutive rises of PSA, 1 week apart, resulting in two 50% increases over the nadir, with PSA > 2 ng/mL.
Or Radiological progression: The appearance of two or more bone lesions on bone scan or enlargement of a soft tissue lesion.
Several studies confirmed the pivotal role of androgen receptors in CRPC. Recent work has shown that the vast majority of castration resistant prostate still relay on androgen receptor activity and recent clinical trials that using agents that directly or indirectly target the androgen receptor have shown clear efficacy.
Also, understanding the molecular structure and function of androgen receptor has allowed for the development of therapies that block the necessary and specific receptor domains.
Over the past decade, the therapeutic options available for men with CRPC have increased markedly. Hormone-related therapies, such as abiraterone and enzalutamide, can significantly prolong overall survival in patients with CRPC and are very well tolerated. Other potent agents that target the AR pathway, such as orteronel, are under evaluation in phase III trials.
Sipuleucel-T is the first immunotherapeutic agent to be effective against prostate cancer and other immunotherapeutic agents, such as ipilimumab (a CTLA4 inhibitor) and PROSTVAC (a poxvirus-based PSA-targeted immunotherapy) are currently under investigation. Docetaxel-based chemotherapy remains a cornerstone in the treatment of mCRPC and cabazitaxel has become the standard second-line chemotherapy. Clinical trials of new agents that can be combined with both of these chemotherapies (in an attempt to further enhance their efficacy) are ongoing.
Osteoclast-targeted agents such as denosumab and zoledronic acid, significantly reduce the risk of SREs in patients with mCRPC. Denosumab was the first bone- targeted agent to show a significant reduction in the incidence of new vertebral fractures in patients with non metastatic hormone-sensitive prostate cancer and it was also the first bone-targeted agent to significantly delay bone metastasis in patients with non metastatic CRPC.
With all these effective therapeutic options and continued research, there is renewed optimism for patients with castration-resistant disease. The challenge for the future will be to establish a rational and evidence- based approach for using these agents to optimize outcomes and minimize costs.