Concluding Remarks

Many options involving the AR, androgens, and their antagonists are available for the treatment of PCa (Fig. 1). Numerous clinical studies have shown equivalent effects on therapeutic benefits by different hormonal treatment strategies. Each treatment strategy/hormonal agent has favorable and unfavorable effects (Table 1). Patients with advanced PCa will clearly benefit from androgen deprivation-based treatments for symptom palliation and improvement of their QOL. However, whether these therapies prolong survival when administered before there are symptoms caused by disease progression remains controversial. Thus, despite a number of previous clinical and experimental studies, finding suitable patients, timing of, and options for hormonal therapy remain problem-atic.121 Data from recent studies support the premise that an earlier treatment in patients' disease course likely leads to better outcomes,82,84,92 but it is not easy to predict the best timing of hormonal therapy for patients with asymptomatic advanced disease. Observation may still be a reasonable choice for these patients.

Currently, available options for hormonal therapy almost never lead to cures in patients with advanced PCa because these patients eventually develop androgen-independent tumors. In addition, another type of failure of hormonal therapy, antiandrogen withdrawal syndrome, has been observed in a significant number (15%—80%) of patients treated with CAB. Although the exact mechanisms for androgen-independent PCa and antiandrogen withdrawal syndrome are far from being fully understood, possible mechanisms were discussed in recent review papers.122'123 To improve overall survival of patients with advanced PCa, novel treatment strategies that prolong the androgen-dependent state, but will not induce antiandrogen withdrawal syndrome, and that are effective against androgen-independent disease, need to be identified. Furthermore, it may be necessary to explore more individualized approaches, such as selectively blocking the activated AR pathway in cancer cells. Finally, second-line hormonal therapy and PCa chemoprevention using hormonal therapy are other interesting topics that are not discussed in this chapter (please refer to Chapter 6 in this volume).

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