雄激素剥夺疗法（ADT）是局部晚期和转移性前列腺癌（PCa）治疗的基石。由于生长激素-胰岛素样生长因子（GH-IGF-1）轴被认为参与了前列腺肿瘤发生，我们旨在评估IGF-1及其结合蛋白与接受ADT治疗的转移性PCa患者的预后之间的关系，包括是否同时使用多西他赛（D）。我们分析了参加第3期CHAARTED试验的接受ADT +/- D治疗的男性患者基线、随机分组后6个月和疾病进展时期的血清样本中的IGF-1及其家族蛋白。主要观察指标是发生去势抵抗性前列腺癌的时间和总生存期（OS）。共有560名患者提供了可供分析的样本。6个月时，ADT+D组的IGF-BP1（平均  +27.4%，p=0.033）、IGF-BP3（平均  +10.3%，p<0.001）和IGF-BP4（平均  +31.1%，p<0.001）显著增加，而ADT组的IGF-BP3（平均  +5.5%，p=0.015）增加。基线和6个月时的较高IGF-1:IGF-BP1比例与ADT组（基线：HR=0.77，p=0.026；6个月：HR=0.83，p=0.036）和ADT+D组（基线：HR=0.78，p=0.04；6个月：HR=0.81，p=0.018）的OS改善有关。基线上log10IGF-1:IGF-BP1比例>1.3的患者，在与先前队列数据的Meta分析中显示着OS改善（HR=0.71）。较高的基线和6个月IGF-1:IGF-BP1比率与更好的OS相关。深入探索IGF-1轴将对评估其作为预测性生物标志物的作用并在治疗试验中针对该轴具有重要意义。

Androgen deprivation therapy (ADT) forms the cornerstone of treatment in locally-advanced and metastatic prostate cancer (PCa). Since the growth hormone-insulin like growth factor (GH-IGF-1) axis has been implicated in prostate tumorigenesis, we aimed to evaluate the association between IGF-1 and its binding proteins on outcomes in men with metastatic PCa treated with ADT, with or without docetaxel (D). We analyzed serum samples for IGF-1 and its family proteins from baseline, 6 months post-randomization and at the time of progression in men enrolled to receive ADT +/- D in the phase 3 CHAARTED trial. The key outcomes were time to development of castrate-resistant prostate cancer and overall survival (OS). 560 patients had samples available for analysis. At 6 months, significant increases in IGF-BP1 (mean +27.4%, p=0.033), IGF-BP 3 (mean +10.3%, p<0.001) and IGF-BP4 (mean +31.1%, p<0.001) were seen in the ADT+D group, while the ADT group showed an increase in IGF-BP3 (mean +5.5%, p=0.015). A higher IGF-1:IGF-BP1 ratio at baseline and after 6 months was associated with improved OS in both the ADT (baseline: HR=0.77, p=0.026; 6 months: HR=0.83, p=0.036) and ADT+D groups (baseline: HR=0.78, p=0.04; 6 months: HR=0.81, p=0.018). Patients with a log10IGF-1:IGF-BP1 ratio >1.3 at baseline had improved OS when meta-analyzed with data from a prior cohort (HR=0.71). Higher baseline and 6-month IGF-1:IGF-BP1 ratio was associated with better OS. Further exploration of the IGF-1 axis will be important to assess its role as a predictive biomarker and to target this axis in therapeutic trials.