Bioquímica Investigación, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain.
Br J Cancer. 2013 Jun 25;108(12):2565-72. doi: 10.1038/bjc.2013.270. Epub 2013 May 30.
Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA).
This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (β-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded.
Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with β-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression.
In patients with PCa and bone metastases treated with ZA, β-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.
由于前列腺癌（PCa）和骨转移治疗的临床数据有效性有限，生化标志物是预测这些患者生存、疾病进展和骨骼相关事件（SREs）的有前途的工具。本研究的目的是评估骨转换生化标志物对接受唑来膦酸（ZA）治疗的 PCa 和骨转移患者的死亡风险、疾病进展和 SREs 的预测能力。
这是一项观察性、前瞻性和多中心研究，共纳入 98 例患者。患者接受 ZA（4 mg，每 4 周一次，共 18 个月）治疗。在治疗开始后 3、6、9、12、15 和 18 个月收集数据。在研究的所有时间点均分析血清骨碱性磷酸酶（BALP）、I 型前胶原氨基端前肽（P1NP）和 I 型胶原羧基端β-肽（β-CTX）的水平。记录疾病进展、SREs 发展和生存数据。
具有临床数据和骨标志物的 Cox 回归模型显示，三种标志物的水平均与生存时间相关，其中β-CTX 的预测能力最强，在治疗开始后第 1 次就诊（3 个月）未正常化的患者的死亡风险比正常化患者高 6.3 倍。这些标志物的水平也可预测 SREs，但在这种情况下，BALP 和 P1NP 被证明是更好的预测指标。我们未发现骨标志物与疾病进展之间存在任何关系。
在接受 ZA 治疗的 PCa 和骨转移患者中，β-CTX 和 P1NP 可作为死亡风险的合适预测指标，而 BALP 和 P1NP 可作为 SREs 的合适预测指标。治疗开始后 3 个月时这些生物标志物的水平尤为重要。
