Abouassaly Robert, Paciorek Alan, Ryan Charles J, Carroll Peter R, Klein Eric A
Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Cancer. 2009 Oct 1;115(19):4470-6. doi: 10.1002/cncr.24526.
Virtually all patients with prostate cancer who receive androgen deprivation therapy (ADT) will ultimately develop evidence of resistance to treatment. The prognosis for patients who develop metastatic castrate-resistant disease is reported to be poor, with overall survival historically estimated to be 24 to 36 months. The goal of the current study was to identify predictors of clinical disease progression in patients with prostate cancer who were receiving ADT.
Of the 13,740 men with biopsy-proven prostate cancer who were enrolled in the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) database from 1995 to 2007, 4003 men treated with ADT after diagnosis without evidence of metastases at treatment initiation were identified. The primary endpoint was the development of bone metastasis. Clinical and pathologic characteristics were compared between patients who developed metastasis and those who did not using chi-square tests in a Cox proportional hazards regression model.
The mean age of the men in the cohort was 70 years (range, 39-94 years). One hundred ninety-one men (4.8%) progressed to metastatic disease at a median of 18 months from the initiation of ADT (range, 1-139 months). On multivariate analyses, risk category (hazards ratio [HR], 2.58; P < .0001), percent of biopsies positive >33% (HR, 3.36; P = .003), age </=65 years at diagnosis (HR, 2.11; P = .001, and prostate-specific antigen velocity on ADT (HR, 1.04; P < .001) were found to be significantly associated with the development of metastatic disease after ADT.
Younger men with high-risk disease appear to have worse prognosis than older men with similar disease. This, along with the other prognostic variables established in the current study, may help identify candidates for clinical trials evaluating secondary treatments for patients with castrate-resistant disease.
几乎所有接受雄激素剥夺治疗（ADT）的前列腺癌患者最终都会出现对治疗耐药的证据。据报道，发生转移性去势抵抗性疾病的患者预后较差，历史上总体生存期估计为24至36个月。本研究的目的是确定接受ADT的前列腺癌患者临床疾病进展的预测因素。
在1995年至2007年纳入前列腺癌战略泌尿研究计划（CaPSURE）数据库的13740例经活检证实为前列腺癌的男性中，确定了4003例诊断后接受ADT且治疗开始时无转移证据的男性。主要终点是骨转移的发生。在Cox比例风险回归模型中，使用卡方检验比较发生转移的患者和未发生转移的患者的临床和病理特征。
该队列中男性的平均年龄为70岁（范围39 - 94岁）。191名男性（4.8%）在开始ADT后的中位时间18个月（范围1 - 139个月）进展为转移性疾病。多因素分析显示，风险类别（风险比[HR]，2.58；P <.0001）、活检阳性率>33%（HR，3.36；P =.003）、诊断时年龄≤65岁（HR，2.11；P =.001）以及ADT期间前列腺特异性抗原速度（HR，1.04；P <.001）与ADT后转移性疾病的发生显著相关。
患有高危疾病的年轻男性似乎比患有类似疾病的老年男性预后更差。这一点，连同本研究中确定的其他预后变量，可能有助于识别适合评估去势抵抗性疾病患者二线治疗的临床试验的候选者。
