ESTABLISHMENT OF TECHNIQUE TO ESTIMATE THE MOST APPROPRIATE METHOD OF ENDOCRINE THERAPY FOR PROSTATE CANCER

前列腺癌的内分泌治疗方法很多，如手术去势、LHRH激动剂、最大雄激素阻断、抗雄激素单药治疗和雌激素治疗。此外，即使雄激素抑制没有显示更多的效果，也进行了几种激素操作，包括停用抗雄激素和给予糖皮质激素。然而，在治疗前很难估计最适合每个患者的方法。因此，为了建立用于确定合适的内分泌治疗的技术，检查了与用内分泌治疗治疗的前列腺癌患者的预后相关的血清标志物、遗传变化和组织病理学特征。治疗前血清睾酮水平和雄激素受体中CAG重复序列的数量被证明是良好的预后因素。高血清嗜铬粒蛋白A和低血清前列腺特异性抗原（PSA）的患者预后差，沿着神经内分泌分化。间歇性雄激素抑制可能与雄激素依赖性肿瘤患者有关，其中雄激素抑制能够通过细胞凋亡导致肿瘤缩小。在间歇治疗期间，血清游离PSA与总PSA的比值可用于确定重新开始治疗的时间。地塞米松治疗对雄激素抑制后进展的患者有效，可能通过降低血清白细胞介素-6水平抑制雄激素受体的配体非依赖性激活。根据患者和肿瘤的临床病理和遗传因素，选择最合适的内分泌治疗方法，实现有序内分泌治疗。

A number of methods have been utilzed as endocrine therapy for prostate cancer, such as surgical castration, LHRH agonist, maximum androgen blockade, antiandrogen-monotherapy, and estrogen. In addition, several hormonal manipulations including withdrawal of antiandrogen and administration of glucocorticoid have been performed even when androgen suppression reveals no more effect. However, it is difficult to estimate the most appropriate method for each patient before the treatment. Thus, to establish the technique for determining the suitable endocrine therapy, serum markers, genetic changes and histopathological characteristics were examined in relation to prognosis in prostate cancer patients treated with endocrine therapy. Pretreatment serum testosterone level and the number of CAG repeat in the androgen receptor were shown to be good prognostic factors. Patients with high level of , serum chromogranin A and low serum prostate specific antigen (PSA) demonstrated poor prognosis along with neuroendocrine differentiation. Intermittent androgen suppression could be implicated for patients with androgen-dependent tumors, in whom androgen suppression were able to result in tumor shrinkage through apoptosis. During intermittent therapy, free-to-total ratio of serum PSA was useful to determine the timing of restart of therapy. Dexamethasone therapy was effective for patients who showed progression after androgen suppression, probably through inhibition of ligand-independent activation of the androgen receptor by decreasing serum interleukin-6 level. The order-made endocrine therapy to select the most appropriate method of endocrine therapy could be achieved based on clinicopathological and genetic factors in both patients and tumors.