Affiliations of authors: Department of Biostatistics and Bioinformatics, (SH, C-YL, EK), and Alliance Statistics and Data Center (SH), Duke University, Durham, NC; Departments of Medicine and Urology, University of California-San Francisco, San Francisco, CA (EJS); Division of Medical Oncology, Duke Prostate Center and the Duke Cancer Institute, Durham, NC (AJA); Departments of Medical Oncology and Urology, Yale University Cancer Center, New Haven, CT (DP); Department of Medical Oncology, San Camillo and Forlanini Hospital, Rome, Italy (CNS); Sanofi, Malvern, PA (LS); Department of Medical Oncology, Georges Pompidou European Hospital, Paris, France (SO); Department of Clinical Studies, Royal Marsden Hospital and Institute of Cancer Research, Surrey, United Kingdom (JdB); Urology Department, Tulane Cancer Center, New Orleans, LA (OS).
J Natl Cancer Inst. 2013 Nov 20;105(22):1729-37. doi: 10.1093/jnci/djt280. Epub 2013 Oct 17.
Several prognostic models for overall survival (OS) have been developed and validated in men with metastatic castration-resistant prostate cancer (mCRPC) who receive first-line chemotherapy. We sought to develop and validate a prognostic model to predict OS in men who had progressed after first-line chemotherapy and were selected to receive second-line chemotherapy.
Data from a phase III trial in men with mCRPC who had developed progressive disease after first-line chemotherapy (TROPIC trial) were used. The TROPIC was randomly split into training (n = 507) and testing (n = 248) sets. Another dataset consisting of 488 men previously treated with docetaxel (SPARC trial) was used for external validation. Adaptive least absolute shrinkage and selection operator selected nine prognostic factors of OS. A prognostic score was computed from the regression coefficients. The model was assessed on the testing and validation sets for its predictive accuracy using the time-dependent area under the curve (tAUC).
The nine prognostic variables in the final model were Eastern Cooperative Oncology Group performance status, time since last docetaxel use, measurable disease, presence of visceral disease, pain, duration of hormonal use, hemoglobin, prostate specific antigen, and alkaline phosphatase. The tAUCs for this model were 0.73 (95% confidence interval [CI] = 0.72 to 0.74) and 0.70 (95% CI = 0.68 to 0.72) for the testing and validation sets, respectively.
A prognostic model of OS in the postdocetaxel, second-line chemotherapy, mCRPC setting was developed and externally validated. This model incorporates novel prognostic factors and can be used to provide predicted probabilities for individual patients and to select patients to participate in clinical trials on the basis of their prognosis. Prospective validation is needed.
已经开发并验证了几种用于转移性去势抵抗性前列腺癌(mCRPC)男性患者的总生存期(OS)的预后模型,这些患者接受一线化疗。我们旨在开发和验证一种预测模型,以预测接受二线化疗的一线化疗后进展的男性患者的 OS。
使用 mCRPC 男性患者的 III 期试验(TROPIC 试验)数据,这些患者在一线化疗后出现疾病进展。TROPIC 随机分为训练集(n = 507)和测试集(n = 248)。另一个由 488 名先前接受多西他赛治疗的男性组成的数据集(SPARC 试验)用于外部验证。适应性最小绝对收缩和选择算子选择了 OS 的九个预后因素。从回归系数计算出预后评分。使用时间依赖性曲线下面积(tAUC)评估模型在测试和验证集上的预测准确性。
最终模型中的九个预后变量为东部合作肿瘤学组表现状态、上次使用多西他赛的时间、可测量疾病、存在内脏疾病、疼痛、激素使用持续时间、血红蛋白、前列腺特异性抗原和碱性磷酸酶。该模型在测试集和验证集上的 tAUC 分别为 0.73(95%置信区间 [CI] = 0.72 至 0.74)和 0.70(95% CI = 0.68 至 0.72)。
在多西他赛二线化疗后 mCRPC 环境中开发并外部验证了 OS 的预后模型。该模型纳入了新的预后因素,可以用于为个体患者提供预测概率,并根据其预后选择患者参加临床试验。需要前瞻性验证。