Guidelines for the management of castrate-resistant prostate cancer (2010)

DefinitionCastrate-resistant prostate cancer (CRPC) is defined by disease progression despite androgen depletion therapy (ADT) and may present as either a continuous rise in serum prostate-specific antigen (PSA) levels, the progression of preexisting disease, and/or the appearance of new metastases.Advanced prostate cancer has been known under a number of names over the years, including hormone-resistant prostate cancer (HRPC) and androgen-insensitive prostate cancer (AIPC).Most recently, the terms CRPC or castration recurrent prostate cancer were introduced with the realization that intracrine/paracrine androgen production plays is significant in the resistant of prostate cancer cells to testosterone suppression therapy. 1 In their second publication, the Prostate Cancer Working Group (PCWG2) 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 a surgical orchidectomy or medical therapy. 2 This continuum creates a clinical-states model where patients can be classified.The rising PSA states (castrate and noncastrate) signify that no detectable (measurable or non-measurable) disease has ever been found.The clinical metastases states (castrate and noncastrate) signify that disease was detectable at some point in the past, regardless of whether it is detectable now.Prognosis is associated with several factors, including performance status, presence of bone pain, extent of disease on bone scan and serum alkaline phosphatase levels.Bone metastases will occur in 90% of men with CRPC and can produce significant morbidity, including pain, pathologic fractures, spinal cord compression and bone marrow failure.Paraneoplastic effects are also common, including anemia, weight loss, fatigue, hypercoagulability and increased susceptibility to infection.CRPC presents a spectrum of disease ranging from patients without metastases or symptoms with rising PSA levels despite ADT, to patients with metastases and significant debilitation due to cancer symptoms. Management of CRPC Secondary hormonal manipulations In patients who develop CRPC and who are relatively asymptomatic, secondary hormonal treatments may be attempted. Level 2 Evidence, Grade C recommendationTo date, no study of secondary hormone treatment has demonstrated benefits in terms of survival, but most trials have been smaller and heavily confounded by the future treatments used.In patients treated with luteinizing-hormonereleasing hormone agonist monotherapy or who have had an orchidectomy, total androgen blockade (TAB) with testosterone antagonists, such as bicalutamide, can offer PSA responses in 30% to 35% of patients.For patients who progress on ADT without evidence of distant metastases, it is suggested to screen them for bone metastases and to monitor them for visceral metastases/progression with abdomen and chest imaging.Exact timing of imaging may be modulated using PSA doubling time.Imaging techniques most commonly used include nuclear bone scans and abdominal computed tomography and chest X-ray.The role of magnetic resonance imaging and positron emission tomography is still unclear.For patients who have undergone TAB, the antiandrogen could be discontinued to exclude an antiandrogen withdrawal response (AAWD).The introduction or changes of an AA or the use of ketoconazole has been reported to have transient PSA reductions in about 30% of patients. 3Level 3 Evidence, Grade C recommendation Because the androgen receptor remains active in most patients who have developed castration resistant disease, it is recommended by groups, such as ASCO (American Society of Clinical Oncology), NCCN (National Comprehensive Cancer Network), CCO (Cancer Care Ontario) and others, that ADT should be continued.Level 3 Evidence, Grade C recommendation Systemic corticosteroid therapy Corticosteroid therapy with low-dose prednisone or dexamethasone may also offer improvements in PSA values and/ cua guideline