Improved Survival in a Cohort of Trial Participants with Metastatic Castration-resistant Prostate Cancer Demonstrates the Need for Updated Prognostic Nomograms
Improved Survival in a Cohort of Trial Participants with Metastatic Castration-resistant Prostate Cancer Demonstrates the Need for Updated Prognostic Nomograms
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DOI：
10.1016/j.eururo.2012.12.029
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发表时间：
2013-08-01
期刊：
影响因子：
23.4
通讯作者：
de Bono, Johann
中科院分区：
文献类型：
--
作者：
Omlin, Aurelius;Pezaro, Carmel;de Bono, Johann
背景：在前多西紫杉醇时代，转移性去势抵抗性前列腺癌（CRPC）患者的中位总生存期（OS）为13-16个月。在引入多西紫杉醇和其他新型治疗方法之前，构建了用于估计CRPC生存的预后图。目的：检验预后模型是否仍能准确反映大量试验参与者的生存。设计、环境和参与者：从2003年6月到2011年12月，我们机构442名CRPC患者在临床试验中接受治疗的生存分析。结果测量和统计分析：将Halabi和Smaletz nomogram预测生存率与观察生存率进行比较。Cox模型多变量分析（MVA）采用转诊时的变量，包括表现状态（PS）；前列腺特异性抗原（PSA）、乳酸脱氢酶（LDH）、碱性磷酸酶（ALP）、血红蛋白（Hb）、白蛋白水平；诊断时存在内脏疾病和转移性疾病。结果和局限性：从转诊点开始，首次化疗患者的中位OS为30.6个月（95%可信区间[CI]， 27.6-36.5个月）。相比之下，使用Halabi和Smaletz模型的预测生存期分别为21个月和18个月。在这些患者中，较差的PS、较低的Hb水平和较高的LDH水平是MVA的最强预测因子。在化疗后转诊的患者中，转诊后的生存率为17.5个月（95% CI, 16.0-19.5个月），LDH水平升高和内脏转移的存在是生存率的最强预测因子。在整个队列中，诊断为CRPC的中位OS为40.7个月（95% CI, 36.8-44.0个月）。临床试验的参与是安全的，死亡率低。这组男性参加了1期、2期和3期试验和扩大的准入项目；他们的数据可能不能反映所有CRPC患者的生存率。结论：由于高效的新疗法对生存的影响，目前使用的预后图需要重新验证其预测CRPC生存的能力。(C) 2012年欧洲泌尿外科协会Elsevier B.V.版权所有。
Background: Median overall survival (OS) in men with metastatic castration-resistant prostate cancer (CRPC) was 13-16 mo in the predocetaxel era. Prognostic nomograms for survival estimation in CRPC were constructed prior to the introduction of docetaxel and other novel treatments.Objective: To examine whether prognostic models still accurately reflect survival in a large cohort of trial participants.Design, setting, and participants: Survival analysis of 442 men with CRPC sequentially treated in clinical trials at our institution from June 2003 to December 2011.Outcome measures and statistical analysis: Predicted survival by Halabi and Smaletz nomograms was compared to observed survival. Cox model multivariate analysis (MVA) used variables at referral, including performance status (PS); levels of prostate-specific antigen (PSA), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), haemoglobin (Hb), and albumin; presence of visceral disease, and metastatic disease at diagnosis.Results and limitations: From point of referral, chemotherapy-naive patients had a median OS of 30.6 mo(95% confidence interval [CI], 27.6-36.5 mo). In contrast, predicted survival using the Halabi and Smaletz models was 21 and 18 mo, respectively. In these patients, poor PS, lower Hb level, and increasing LDH level were the strongest predictors in the MVA. In patients referred after chemotherapy, survival from referral was 17.5 mo (95% CI, 16.0-19.5 mo) and increasing LDH level and presence of visceral metastases were the strongest predictors of survival. Median OS from diagnosis of CRPC was 40.7 mo in the overall cohort (95% CI, 36.8-44.0 mo). Clinical trial participation was safe, with low mortality rate.This cohort of men participated in phase 1, 2 and 3 trials and expanded access programs; their data may not reflect survival in all CRPC patients.Conclusions: Due to the impact of highly effective novel therapies on survival, prognostic nomograms in current use require revalidation regarding their ability to predict survival in CRPC. (C) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.