Systemic nonhormonal management of advanced prostate cancer and its likely impact on patients' survival and quality of life

Prostate cancer is a hormonal sensitive disease with a response rate ranging from 80 to 90%; however, the majority of patients develop hormone resistance resulting in poor long term survival. Chemotherapy has demonstrated a benefit over steroids in improving the quality of life in the hormone refractory phase. Furthermore, the introduction of docetaxel succeeded in improving the survival of these patients in first-line therapy. Second-line treatment following docetaxel is challenging with no agent classified as standard in this setting. In the last 5 years, several drugs have shown promising results in initial evaluation. However, randomized phase III trials would be needed to answer this question. The majority of patients develop bone metastasis and the use of bisphosphonates has yielded encouraging results. Our understanding of the biology of hormone refractory prostate cancer has improved dramatically over the past few years and has translated into the developments of new therapeutic targets for this disease. Agents affecting several targets, including calcitriol, endotheline-1, bcl-2, and angiogenesis, are being studied currently and have the potential to change the treatment paradigms of this otherwise fatal disease. This review focuses on current and potential treatment options, including cytotoxic agents, bisphosphonates, and targeted agents, for patients with hormone refractory prostate cancer and the impact of these options on survival and quality of life.