Abstract

Castration-resistant prostate cancer (CRPC) is defined by disease progression despite castrate levels 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. Advanced prostate cancer has been known under a few names over the years, including hormone-resistant prostate cancer (HRPC) and androgen-insensitive prostate cancer (AIPC). Most recently, the terms castration-resistant prostate cancer or castration-recurrent prostate cancer were introduced with the realization that extra-testicular androgen production plays a significant role in the resistance of prostate cancer cells to medical or surgical castration therapy.1 In their second publication, the Prostate Cancer Working Group defined CRPC as a continuum on the basis of whether metastases are detectable (clinically or by imaging) and whether the serum testosterone is in the castrate range by surgical orchidectomy or medical therapy.2 This definition creates a clinical-states model, where patients can be classified. The rising PSA states (castrate and non-castrate) signify that no detectable (measurable or non-measurable) disease has ever been found. The clinical metastases states (castrate and non-castrate) signify that disease was detectable at some point in the past, regardless of whether it is detectable now.3 Prognosis is associated with several factors that go beyond PSA levels. These include performance status, presence of visceral metastases, presence of bone pain, extent of disease on bone scan, and serum lactate dehydrogenase and alkaline phosphatase levels. Bone metastases will occur in 90% of men with CRPC and can produce significant morbidity, including pain, pathological fractures, spinal cord compression, and bone marrow failure. Paraneoplastic effects, including anemia, weight loss, fatigue, hypercoagulability, and increased susceptibility to infection, are also common. CRPC includes patients without metastases or symptoms with rising PSA levels despite androgen-deprivation therapy (ADT) to patients with metastases and significant debilitation due to cancer symptoms.

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