Metastasis-Free Survival Is a Strong Surrogate of Overall Survival in Localized Prostate Cancer
Metastasis-Free Survival Is a Strong Surrogate of Overall Survival in Localized Prostate Cancer
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DOI：
10.1200/jco.2017.73.9987
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发表时间：
2017-09-20
影响因子：
45.3
通讯作者：
Sweeney, Christopher J.
中科院分区：
文献类型：
--
作者：
Xie, Wanling;Regan, Meredith M.;Sweeney, Christopher J.
目的：中危和高危局限性前列腺癌的辅助治疗可减少该病的死亡人数。总生存率（OS）的替代品，可以加快新的辅助therapy.MethodsBy 2013年6月，102个完成或正在进行的随机试验，确定和个人患者的数据收集28项试验，28,905例患者的评价。分别确定了来自24项试验的21，140例患者和来自19项试验的12，712例患者的无疾病生存期（DFS）和无转移生存期（MFS）。我们使用两阶段荟萃分析验证模型，通过确定中间临床终点与OS的相关性以及中间临床终点和OS.ResultsTrials治疗效果的相关性，评估DFS和MFS对OS的替代性。在中位随访10年后，21，140名男性中有45%和12，712名男性中有45%分别经历了DFS和MFS事件。对于DFS和MFS，分别有61%和90%的患者来自放射试验，分别有63%和66%的患者患有高危疾病。在患者水平，DFS和MFS的Kendall相关性分别为0.85和0.91。在试验水平，8年OS率与5年DFS和MFS率的加权线性回归的R-2分别为0.86（95% CI，0.78 - 0.90）和0.83（95% CI，0.71 - 0.88）。用对数危险比测量的替代物和OS的治疗效果有很好的相关性（DFS的R-2为0.73 [95%CI为0.53 ~ 0.82]，MFS为0.92 [95%CI为0.81 ~ 0.95]）。
PurposeAdjuvant therapy for intermediate-risk and high-risk localized prostate cancer decreases the number of deaths from this disease. Surrogates for overall survival (OS) could expedite the evaluation of new adjuvant therapies.MethodsBy June 2013, 102 completed or ongoing randomized trials were identified and individual patient data were collected from 28 trials with 28,905 patients. Disease-free survival (DFS) and metastasis-free survival (MFS) were determined for 21,140 patients from 24 trials and 12,712 patients from 19 trials, respectively. We evaluated the surrogacy of DFS and MFS for OS by using a two-stage meta-analytic validation model by determining the correlation of an intermediate clinical end point with OS and the correlation of treatment effects on both the intermediate clinical end point and OS.ResultsTrials enrolled patients from 1987 to 2011. After a median follow-up of 10 years, 45% of 21,140 men and 45% of 12,712 men experienced a DFS and MFS event, respectively. For DFS and MFS, 61% and 90% of the patients, respectively, were from radiation trials, and 63% and 66%, respectively, had high-risk disease. At the patient level, Kendall's correlation with OS was 0.85 and 0.91 for DFS and MFS, respectively. At the trial level, R-2 was 0.86 (95% CI, 0.78 to 0.90) and 0.83 (95% CI, 0.71 to 0.88) from weighted linear regression of 8-year OS rates versus 5-year DFS and MFS rates, respectively. Treatment effectsmeasured by log hazard ratiosfor the surrogates and OS were well correlated (R-2, 0.73 [95% CI, 0.53 to 0.82] for DFS and 0.92 [95% CI, 0.81 to 0.95] for MFS).ConclusionMFS is a strong surrogate for OS for localized prostate cancer that is associated with a significant risk of death from prostate cancer.