**Part 4**

**Medical Management and Its Therapeutic Implications** 

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Sweden

**12** 

**Current Options and** 

*University of Toronto* 

*Canada* 

**Future Directions in Castrate** 

*Department of Medical Oncology, Princess Margaret Hospital* 

Prostate cancer is the most frequently diagnosed malignancy in North America and second leading cause of cancer-related death (Jemal *et al.*, 2010). Despite effective local therapy, prostate cancer often recurs. Standard therapy for recurrent or metastatic prostate cancer remains androgen deprivation therapy (ADT) which is highly effective but not durable (Sharifi *et al.*, 2005). All patients will eventually progress to castrate resistant prostate cancer (CRPC) where there are few treatment options and until recently survival was a dismal 12- 18 months (Tannock *et al.*, 1996). In this chapter we will review the current treatment approaches for CRPC, but focus primarily on the newly approved options available in the

Castrate-resistant prostate cancer (CRPC) is defined as prostate cancer progression despite ADT and may present with either increasing serum prostate-specific antigen (PSA) levels, radiologic progression, and/or the appearance of new metastases (Saad and Hotte, 2010). Over the years, advanced prostate cancer has been referred to as hormoneresistant prostate cancer (HRPC) or androgen-insensitive prostate cancer (AIPC), but the name has changed to CRPC to reflect the fact that intracrine/paracrine androgen production and signaling pathways play an important role in mediating resistance to first line ADT. CRPC presents as a spectrum of diseases ranging from patients with rising PSA alone, without metastases or symptoms to patients with rising PSA, progressive metastatic disease and significant symptoms. In patients who develop CRPC and who are relatively asymptomatic, secondary hormonal treatments may be attempted. To date, no study of secondary hormone treatment has demonstrated survival benefits, but most trials have been small, underpowered and confounded by the use of subsequent treatments. In patients who are progressing on ADT, discontinuation of antiandrogens, introduction of low dose prednisone or ketoconazole to block production of adrenal androgens, can offer transient PSA responses and palliative benefits in 30% to 35% of patients (Storlie *et al.*,

For CRPC patients with symptoms, rapid PSA progression or visceral disease, docetaxel chemotherapy and prednisone is currently considered standard of care. Docetaxel is a

**1. Introduction** 

post-docetaxel setting.

1995; Small *et al.*, 2004; Heng and Chi, 2006).

**Resistant Prostate (CRPC)** 

Suzanne Richter and Srikala S. Sridhar
