Evaluation for surrogacy of end points by using data from observational studies: Tumor downstaging for evaluating neoadjuvant chemotherapy in invasive bladder cancer
Evaluation for surrogacy of end points by using data from observational studies: Tumor downstaging for evaluating neoadjuvant chemotherapy in invasive bladder cancer
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DOI：
10.1158/1078-0432.ccr-05-1598
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发表时间：
2006-01-01
影响因子：
11.5
通讯作者：
Fukushima, M
中科院分区：
文献类型：
--
作者：
Teramukai, S;Nishiyama, H;Fukushima, M
目的：在评估新辅助化疗的临床癌症试验中，肿瘤分期下调经常被用作总生存期的替代终点。我们评估了代孕的肿瘤降级使用的数据，从后续的观察性研究在bladder cancer.Experimental Design：共586例患者（来自32家日本医院）进行根治性膀胱切除术浸润性膀胱癌（临床T2至T4）在1990年和2000年之间进行了分析。我们将诊断时临床分期和术后病理分期随时间的变化作为替代终点，将术后生存时间作为真实终点。首先，我们开发了一种新的肿瘤降级标准。其次，我们统计学评估代孕的标准使用普伦蒂斯的criterions.Results：开发的标准的终点的基础上肿瘤的降级，我们选择了最好的分类在所有可能的分类，试图分离患者的预后。调整预后因素后，中效组和差效组与良效组相比的风险比分别为1.9（95%可信区间，1.0-3.7）和5.0（95%可信区间，2.6-9.8）。普伦蒂斯准则的相关性和条件独立性条件近似满足。新辅助化疗具有统计学显著的肿瘤降级效果，而治疗组之间的生存率没有差异。结论：肿瘤降级效果可能是一个合适的中间终点筛选新的新辅助化疗浸润性膀胱癌。随访研究的数据集可用于评价终点的替代性。
Purpose: In clinical cancer trials for evaluating neoadjuvant chemotherapy, tumor downstaging is frequently used as a surrogate end point for overall survival. We evaluated the surrogacy of tumor downstaging using data from a follow-up observational study in bladder cancer.Experimental Design: A total of 586 patients (from 32 Japanese hospitals) who underwent radical cystectomy for invasive bladder cancer (clinical T2 to T4) between 1990 and 2000 were analyzed. We considered changes over time in clinical stage at diagnosis and pathologic stage at cystectomy as a surrogate end point, and survival time after cystectomy as a true end point. First, we developed a new criterion for tumor downstaging. Second, we statistically evaluated surrogacy for the criterion using Prentice's criteria.Results:To develop the criterion of end points based on tumor downstaging, we selected the best classification among all possible classifications in an attempt to separate prognosis for patients. The hazard ratios after adjustment for prognostic factors in the intermediate effect patients and the poor effect patients were 1.9 (95% confidence interval, 1.0-3.7) and 5.0 (95% confidence interval, 2.6-9.8), respectively, compared with that in the good effect patients. The conditions for correlation and conditional independency of Prentice's criteria were satisfied approximately. Neoadjuvant chemotherapy has a statistically significant tumor downstaging effect, whereas there was no difference on survival between treatment groups.Conclusions: The tumor downstaging effect could be an appropriate intermediate end point for screening novel neoadjuvant chemotherapy for invasive bladder cancer. The dataset from follow-up studies were useful for evaluating the surrogacy of end points.