前列腺特异性抗原失败后挽救性激素治疗的前列腺癌特异性死亡率的中间终点。

Intermediate end point for prostate cancer-specific mortality following salvage hormonal therapy for prostate-specific antigen failure.

作者信息

D'Amico Anthony V, Moul Judd W, Carroll Peter R, Cote Kerri, Sun Leon, Lubeck Deborah, Renshaw Andrew A, Loffredo Marian, Chen Ming-Hui

机构信息

Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115, USA.

出版信息

J Natl Cancer Inst. 2004 Apr 7;96(7):509-15. doi: 10.1093/jnci/djh086.

DOI:10.1093/jnci/djh086

PMID:15069112

Abstract

BACKGROUND

Whether the prostate-specific antigen (PSA) response to salvage hormonal therapy can act as an intermediate end point for prostate cancer-specific mortality (PCSM) remains unclear. Therefore, we evaluated whether PSA response, defined as the absolute value of the ratio of the rate of PSA change after salvage hormonal therapy to the rate of PSA change before salvage therapy, is associated with the time to PCSM following salvage hormonal therapy.

METHODS

A single-institution and two pooled multi-institution databases containing baseline, treatment, and follow-up information on men who received salvage hormonal therapy for PSA failure following surgery or radiation therapy from January 1, 1988, to January 1, 2002, formed the study (n = 199) and validation cohorts (n = 1255), respectively. The ability of PSA response and its constituents (i.e., pre-salvage hormonal therapy PSA slope and post-salvage hormonal therapy PSA slope) to predict time to PCSM following salvage hormonal therapy was assessed using Cox regression analysis. For illustrative purposes, PSA response was analyzed as a dichotomous variable with a breakpoint for the ratio of PSA response of 1. All statistical tests were two-sided.

RESULTS

PSA response was statistically significantly associated with time to PCSM following salvage hormonal therapy in both the study (P(Cox) =.0014) and validation (P(Cox)<.001) cohorts; however, its constituents were not (pre-salvage hormonal therapy PSA slope: P(Cox-study) =.97, P(Cox-validation) =.57; post-salvage hormonal therapy PSA slope: P(Cox-study) =.27, P(Cox-validation) =.31). Patients with a PSA response that was less than or equal to 1 had a statistically significantly shorter time to PCSM than patients with a PSA response of greater than 1 in both the study (hazard ratio [HR] = 3.6, 95% confidence interval [CI] = 1.3 to 10.3; P(Cox) =.01) and validation (HR = 12.8, 95% CI = 6.2 to 26.3; P(Cox)<.001) cohorts.

CONCLUSION

The PSA response to salvage hormonal therapy can serve as an intermediate end point for PCSM in patients with a rising PSA level following surgery or radiation therapy.

摘要

背景

前列腺特异性抗原（PSA）对挽救性激素治疗的反应能否作为前列腺癌特异性死亡率（PCSM）的一个中间终点仍不明确。因此，我们评估了PSA反应（定义为挽救性激素治疗后PSA变化率与挽救性治疗前PSA变化率之比的绝对值）是否与挽救性激素治疗后至PCSM的时间相关。

方法

一个单机构数据库和两个汇总的多机构数据库，分别构成了研究队列（n = 199）和验证队列（n = 1255），这些数据库包含了1988年1月1日至2002年1月1日因手术或放疗后PSA失败而接受挽救性激素治疗的男性的基线、治疗及随访信息。使用Cox回归分析评估PSA反应及其组成部分（即挽救性激素治疗前PSA斜率和挽救性激素治疗后PSA斜率）预测挽救性激素治疗后至PCSM时间的能力。为便于说明，将PSA反应作为一个二分变量进行分析，PSA反应比值的分界点为1。所有统计检验均为双侧检验。

结果

在研究队列（P(Cox)=.0014）和验证队列（P(Cox)<.001）中，PSA反应与挽救性激素治疗后至PCSM的时间均有统计学显著相关性；然而，其组成部分并无相关性（挽救性激素治疗前PSA斜率：P(Cox - 研究)=.97，P(Cox - 验证)=.57；挽救性激素治疗后PSA斜率：P(Cox - 研究)=.27，P(Cox - 验证)=.31）。在研究队列（风险比[HR]=3.6，95%置信区间[CI]=1.3至10.3；P(Cox)=.01）和验证队列（HR = 12.8，95% CI = 6.2至26.3；P(Cox)<.001）中，PSA反应小于或等于1的患者至PCSM的时间在统计学上显著短于PSA反应大于1的患者。