Sidney Kimmel Comprehensive Cancer Center.
Ann Oncol. 2013 Nov;24(11):2881-6. doi: 10.1093/annonc/mdt335. Epub 2013 Aug 14.
Clinical trials in men with biochemically recurrent prostate cancer (BRPC) have been hampered by long survival times, making overall survival (OS) a difficult end point to reach. Intermediate end points are needed in order to conduct such trials within a more feasible time frame.
This is a retrospective analysis of 450 men with BRPC following prostatectomy treated at a single institution between 1981 and 2010, of which 140 developed subsequent metastases. Androgen deprivation therapy (ADT) was deferred until after the development of metastases. Cox regression models were developed to investigate factors influencing OS.
Median metastasis-free survival (MFS) was 10.2 years [95% confidence interval (CI) 7.6-14.0 years]; median OS after metastasis was 6.6 years (95%CI 5.8-8.4 years). Multivariable Cox regressions identified four independently prognostic variables for OS: MFS (HR 0.77; 95% CI 0.63-0.94), number of metastases (≤3 versus ≥4; HR 0.50; 95% CI 0.29-0.85), pain (absent versus present; HR 0.43; 95% CI 0.25-0.72), and bisphosphonate use (yes versus no; HR 0.60; 95% CI 0.37-0.98).
MFS emerged as an independent predictor of OS in men with BRPC treated with deferred ADT after the development of metastases. MFS may be a reasonable intermediate end point in future clinical trials. This observation requires prospective validation.
在生化复发前列腺癌(BRPC)的男性中进行临床试验受到长期生存时间的阻碍,使得总生存(OS)成为难以达到的终点。为了在更可行的时间框架内进行此类试验,需要使用中间终点。
这是对 1981 年至 2010 年间在一家机构接受前列腺切除术治疗后发生 BRPC 的 450 名男性的回顾性分析,其中 140 名患者发生了随后的转移。去势治疗(ADT)在转移发生后才开始。建立 Cox 回归模型以研究影响 OS 的因素。
无转移生存(MFS)的中位时间为 10.2 年[95%置信区间(CI)7.6-14.0 年];转移后 OS 的中位时间为 6.6 年(95%CI 5.8-8.4 年)。多变量 Cox 回归分析确定了 OS 的四个独立预后因素:MFS(HR 0.77;95%CI 0.63-0.94)、转移数量(≤3 与≥4;HR 0.50;95%CI 0.29-0.85)、疼痛(无与有;HR 0.43;95%CI 0.25-0.72)和双膦酸盐使用(是与否;HR 0.60;95%CI 0.37-0.98)。
在接受转移性 ADT 延迟治疗的 BRPC 男性中,MFS 是 OS 的独立预测因素。MFS 可能是未来临床试验的合理中间终点。这一观察结果需要前瞻性验证。