Metwalli Adam R, Rosner Inger L, Cullen Jennifer, Chen Yongmei, Brand Timothy, Brassell Stephen A, Lesperance James, Porter Christopher, Sterbis Joseph, McLeod David G
Urologic Oncology Branch, National Cancer Institute, NIH, Bethesda, MD.
Urologic Oncology Branch, National Cancer Institute, NIH, Bethesda, MD.
Urol Oncol. 2014 Aug;32(6):761-8. doi: 10.1016/j.urolonc.2014.03.024. Epub 2014 Jun 11.
In patients with a rising prostate-specific antigen (PSA) level during treatment with androgen deprivation therapy, identification of men who progress to bone metastasis and death remains problematic. Accurate risk stratification models are needed to better predict risk for bone metastasis and death among patients with castration-resistant prostate cancer (CRPC). This study evaluates whether alkaline phosphatase (AP) kinetics predicts bone metastasis and death in patients with CRPC.
A retrospective cohort study of 9,547 patients who underwent treatment for prostate cancer was conducted using the Center for Prostate Disease Research Multi-center National Database. From the entire cohort, 347 were found to have CRPC and, of those, 165 had 2 or more AP measurements during follow-up. To determine the AP velocity (APV), the slope of the linear regression line of all AP values was plotted over time. Rapid APV was defined as the uppermost quartile of APV values, which was found to be ≥6.3 IU/l/y. CRPC was defined as 2 consecutive rising PSA values after achieving a PSA nadir<4 ng/ml and documented testosterone values less than 50 ng/dl. The primary study outcomes included bone metastasis-free survival (BMFS) and overall survival (OS).
Rapid APV and PSA doubling time (PSADT) less than 10 months were strong predictors of both BMFS and OS in a multivariable analysis. Faster PSADT was a stronger predictor for BMFS (odds ratio [OR] = 12.1, P<0.0001 vs. OR = 2.7, P = 0.011), whereas rapid APV was a stronger predictor of poorer OS (OR = 5.11, P = 0.0001 vs. OR = 3.98, P = 0.0034). In those with both a rapid APV and a faster PSADT, the odds of developing bone metastasis and death exceeded 50%.
APV is an independent predictor of OS and BMFS in patients with CRPC. APV, in conjunction with PSA-based clinical parameters, may be used to better identify patients with CRPC who are at the highest risk of metastasis and death. These findings need validation in prospective studies.
在接受雄激素剥夺治疗期间前列腺特异性抗原（PSA）水平升高的患者中，识别进展为骨转移和死亡的男性患者仍然存在问题。需要准确的风险分层模型来更好地预测去势抵抗性前列腺癌（CRPC）患者发生骨转移和死亡的风险。本研究评估碱性磷酸酶（AP）动力学是否能预测CRPC患者的骨转移和死亡。
使用前列腺疾病研究中心多中心国家数据库对9547例接受前列腺癌治疗的患者进行了一项回顾性队列研究。在整个队列中，发现347例患有CRPC，其中165例在随访期间进行了2次或更多次AP测量。为了确定AP速度（APV），绘制所有AP值随时间变化的线性回归线的斜率。快速APV定义为APV值的上四分位数，发现其≥6.3 IU/l/y。CRPC定义为在PSA最低点<4 ng/ml且记录的睾酮值小于50 ng/dl后，PSA值连续两次升高。主要研究结局包括无骨转移生存期（BMFS）和总生存期（OS）。
在多变量分析中，快速APV和PSA倍增时间（PSADT）小于10个月是BMFS和OS的强有力预测指标。更快的PSADT是BMFS的更强预测指标（比值比[OR]=12.1，P<0.0001，而OR=2.7，P=0.011），而快速APV是较差OS的更强预测指标（OR=5.11，P=0.0001，而OR=3.98，P=0.0034）。在同时具有快速APV和更快PSADT的患者中，发生骨转移和死亡的几率超过50%。
APV是CRPC患者OS和BMFS的独立预测指标。APV与基于PSA的临床参数相结合，可用于更好地识别具有最高转移和死亡风险的CRPC患者。这些发现需要在前瞻性研究中进行验证。
