p53 protein expression status and recurrence in men treated with radiation and androgen suppression therapy for higher-risk prostate cancer: A prospective phase II cancer and leukemia group B study (CALGB 9682)
p53 protein expression status and recurrence in men treated with radiation and androgen suppression therapy for higher-risk prostate cancer: A prospective phase II cancer and leukemia group B study (CALGB 9682)
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DOI：
10.1016/j.urology.2007.11.005
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发表时间：
2008-05-01
期刊：
影响因子：
2.1
通讯作者：
Kantoff, Philip W.
中科院分区：
文献类型：
--
作者：
D'Amico, Anthony V.;Halabi, Susan;Kantoff, Philip W.
目的据推测，p53蛋白表达异常与放射（RT）和雄激素抑制治疗（AST）后预后较差有关。方法1997年5月至2001年4月，180例临床分期为T1 c-T3 cN 0 M0前列腺癌的男性患者在一项研究中登记，该研究评估了新辅助（n）AST治疗期间直肠内磁共振成像（eMRI）定义的肿瘤体积（TV）变化是否与前列腺特异性抗原（PSA）结果相关。其中，141例有足够的组织进行p53蛋白表达状态的免疫组化检测，113例有完整的eMRI信息。多变量考克斯回归分析用于评估p53蛋白表达状态是否预测PSA失败的时间，调整已知的预后因素。结果在中位随访6.9年并调整PSA水平、Gleason评分、临床分期和nAST期间eMRI定义的TV变化后，与正常相比，p53表达异常的男性PSA失败的风险增加（风险比[HR]：2.8; 95%置信区间[CI]：1.3-5.9; P = 0.008，141例; HR：2.4; 95% CI：1.1-5.4; P = 0.03，113例）。与正常p53表达相比，PSA失败的校正估计值在异常的男性中显著更高（P = 0.03）。在5年时，这些估计值分别为33%和18%.CONCLUSIONS最大限度的局部对照和随机试验，评估增加新的药物，最大限度的局部治疗对生存的影响是必要的男性前列腺癌表现出异常的p53表达。
OBJECTIVES It has been hypothesized that abnormal p53 protein expression is associated with a worse prognosis after radiation (RT) and androgen suppression therapy (AST). This hypothesis was prospectively tested.METHODS Between May 1997 and April 2001, 180 men with clinical stage T1c-T3cN0M0 adenocarcinoma of the prostate were registered on a study evaluating whether the endorectal magnetic resonance imaging (eMRI)-defined change in tumor volume (TV) during neoadjuvant (n) AST was associated with prostate-specific antigen (PSA) outcome. Of these, 141 had sufficient tissue to perform immunohistochemical detection of the p53 protein expression status and 113 had complete eMRI information. Multivariable Cox regression analysis was used to assess whether p53 protein expression status predicted time to PSA failure adjusting for known prognostic factors.RESULTS After a median follow-up of 6.9 years and adjusting for PSA level, Gleason score, clinical stage, and eMRI-defined TV change during nAST, men with abnormal compared with normal p53 expression were at increased risk of PSA failure (hazard ratio [HR]: 2.8; 95% confidence interval [CI]: 1.3-5.9; P = 0.008 for the 141; HR: 2.4; 95% Cl: 1.1-5.4; P = 0.03 for the 113). Adjusted estimates of PSA failure were significantly higher (P = 0.03) in men with abnormal compared with normal p53 expression. At 5 years, these respective estimates were 33% and 18%.CONCLUSIONS Maximizing local control and randomized trials evaluating the impact on survival of adding novel agents to maximal local therapy are warranted in men whose prostate cancer demonstrates abnormal p53 expression.