COMBINED MODALITY APPROACH FOR PROSTATE CANCER

临床局限性前列腺癌的治疗仍然是 争议 前列腺癌的手术切除（根治性） 切除术）已被证明是有效的治疗，如果癌症是 病理上局限于前列腺。 然而，术前临床 分期往往低估了疾病的病理程度， 手术切缘或前列腺外肿瘤阳性率高 手术后发现。 这引起了对适当性的关注。 根治性直肠癌切除术在一组重要的临床局限性 肿瘤的 这项研究计划的重点是一种创新的治疗策略 旨在改善临床上患有 局限性前列腺癌 具体而言，该战略包括 采用主要激素操作的联合模式方法， 通过手术切除临床上局限的前列腺癌。 的 我们建议的具体目标是： (1)To检查术前激素操作的好处， 临床局限性前列腺癌的病理降级。 这将 通过一项前瞻性随机试验， 接受3个月治疗的研究组之间的疾病病理阶段 Zoladex和Fluoride治疗后行根治性直肠癌切除术与 对照组仅行根治性膀胱切除术。 (2)To前瞻性地确定生物学肿瘤参数的价值， 预测前列腺癌对激素调控的反应， 最后的病理阶段。 待研究的生物学参数为： 类固醇激素受体表达（免疫组化分析） 雄激素、雌激素和孕激素受体），肿瘤增殖 活性和DNA含量（DNA倍性、S和 G2-M期，Ki-67免疫流式细胞术），以及分化和治疗- 相关表型（PSA、PAP、神经内分泌标志物和MDR）。 这些 将对治疗前前列腺活检和治疗后前列腺活检进行评估， 根治性切除标本的治疗。 (3)To描述人前列腺肿瘤中发生的生物学变化 与雄激素戒断相关的类固醇激素 受体表达、肿瘤增殖活性和分化， 治疗相关表型。 这些研究的目的是（1）确定 前列腺肿瘤特异性生物学特性的改变 关于激素操纵和（2）亚- 一群恶性细胞，能够在完成后存活。 雄激素消除 这将提供有关 雄激素非依赖性前列腺癌的生物学。

The treatment of clinically localized prostate cancer remains controversial. Surgical extirpation of prostatic carcinoma (radical prostatectomy) has proven to be effective therapy if cancer is pathologically confined to the prostate. However, pre-surgical clinical staging frequently underestimates the pathologic extent of disease leading to a high rate of positive surgical margins or extraprostatic tumor discovered after surgery. This has raised concerns on the appropriateness of radical prostatectomy in a significant group of clinically localized tumors. This research proposal is focused on an innovative therapeutic strategy designed to improve current treatment results of patients with clinically localized prostate cancer. Specifically, the strategy consists of a combined modality approach employing primary hormonal manipulation followed by surgical resection of clinically localized prostatic carcinoma. The specific aims of our proposal are: (1)To examine the benefit of pre-operative hormonal manipulation in the pathologic downstaging of clinically localized prostate cancer. This will be accomplished through a prospective randomized trial comparing final pathologic stage of disease between the study group receiving 3 months of Zoladex and Flutamide treatment followed by radical prostatectomy versus the control group undergoing radical prostatectomy alone. (2)To prospectively determine the value of biological tumor parameters in predicting the response of prostatic cancer to hormonal manipulation and final pathologic stage. The biological parameters to be studied are: steroid hormone receptor expression (immunohistochemical analysis of androgen, estrogen and progesterone receptors), tumor proliferative activity and DNA content (flowcytometric determination of DNA ploidy, S and G2-M phases, Ki-67 immunoflowcytometry), and differentiation and therapy- associated phenotypes (PSA, PAP, neuroendocrine markers and MDR). These assessments will be performed on pre-therapy prostatic biopsies and post- therapy radical prostatectomy specimens. (3)To characterize the biologic changes occurring in human prostatic tumors associated with androgen withdrawal with respect to steroid hormone receptor expression, tumor proliferative activity and differentiation and therapy-associated phenotypes. These studies are aimed at (1) identifying the changes in specific biologic characteristics of prostatic tumors with respect to hormonal manipulation and (2) characteristics of the sub- population of malignant cells that are able to survive following complete androgen ablation. This will provide valuable information regarding the biology of androgen-independent prostate cancer.