Introduction

Maximal androgen ablation through combination therapy increases treatment-related side effects and expenses and fails to prolong time to progression to androgen-independence and, furthermore, preliminary evidence indicates that a low androgen milieu is associated with tumor aggressiveness. Transition to androgen-independence is a complex process and involves both selection and outgrowth of preexisting androgen-resistant clones, as well as adaptative upregulation of genes that enable cancer cells to survive and grow after CAS [18]. CAS in men with prostate cancer increases the risk of osteoporotic fractures, type 2 diabetes and, possibly, cardiovascular events [19]. The benefits of CAS in treating non-metastatic prostate cancer need to be carefully weighed against the risks of CAS-induced adverse events. Management of the metabolic sequelae of CAS includes optimal reduction of cardiovascular risk factors, with particular attention to weight, blood pressure, lipid profile, smoking cessation and glycemic control. Supported by preclinical and first clinical IAS results, several centers tested the feasibility of IAS in non-randomized groups of prostate cancer patients with serum PSA as trigger point followed by a number of extended phase II and III trials [16,20]

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