COMBINED MODALITY APPROACH FOR PROSTATE CANCER

临床局限性前列腺癌的治疗 有争议的。前列腺癌根治术(根治术) 前列腺癌)已被证明是有效的治疗方法，如果癌症是 病理上局限于前列腺。然而，手术前的临床 分期往往低估了导致疾病的病理程度 手术切缘或前列腺外肿瘤的阳性率很高 在手术后发现的。这引发了人们对其适当性的担忧 根治性前列腺癌根治术在临床上有显著的局限性 肿瘤。 这项研究建议的重点是一种创新的治疗策略 旨在改善目前临床上慢性阻塞性肺疾病患者的治疗效果 局限性前列腺癌。具体地说，该战略包括一个 采用初级荷尔蒙操作的联合模式治疗 通过手术切除临床局限性前列腺癌。这个 我们建议的具体目标是： (1)检验术前荷尔蒙调节的益处 临床局限性前列腺癌的病理分级。这将是 通过比较最终结果的前瞻性随机试验来完成 病理分期的研究组之间接受3个月的 唑拉德克斯和氟他胺治疗前列腺癌根治术与 对照组单纯行前列腺癌根治术。 (2)前瞻性确定肿瘤生物学参数在临床中的价值 预测前列腺癌对激素调节的反应和 最后的病理阶段。拟研究的生物学参数包括： 类固醇激素受体表达(免疫组织化学分析 雄激素、雌激素和孕激素受体)，肿瘤增殖 活性和DNA含量(流式细胞术DNA倍体测定，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 将对治疗前和治疗后的前列腺活检进行评估。 治疗前列腺癌根治术标本。 (3)描述人前列腺肿瘤的生物学变化 与雄激素戒断有关的类固醇激素 受体表达、肿瘤增殖活性和分化及 与治疗相关的表型。这些研究的目的是(1)确定 前列腺癌特异性生物学特性的变化 关于荷尔蒙的操纵和(2)亚 完全性死亡后仍能存活的恶性细胞群 雄激素消融。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.