OPTIMAL SCREENING FOR PROSTATE CA WITH SERIAL PSA LEVELS

描述（申请人的描述）本试点研究的目标是 开发一种早期检测前列腺癌（CP）的方法 即，当与标准方法相比时， 结果是在给定的时间内， 增量测试 主要研究人员目前正在开发 使用数据的长期纵向PSA行为的精确统计模型 来自退伍军人事务部（VA）规范老化研究（NAS）的参与者 作为目前资助的研究的一部分。 在分配假设之后 这些模型已经过测试，我们将使用它们来开发一个优化的 早期检测方法，重新评估患者 前列腺癌在每次连续PSA测量后，基于所有先前 测量. 下一步的决定，无论是活检还是什么时候 下一次PSA测试是基于当前的风险评估。 那些在 升高的风险将更频繁地测量PSA水平， 风险最高的患者需要进行更具侵入性的诊断检查， 活检 因此，更多的筛查资源被分配给那些 增加风险。 对于中等风险组，至下一次PSA的时间 将优化测量以最大限度地延长预期寿命， 使用已发表的按阶段和年龄划分的治疗效果估计值。 的 方法将分为三个阶段：（一）统计方法， 基于单个或多个纵向PSA估计CP的风险 水平，以及PSA水平之间的持续时间将被开发，（II）A 计算机模拟的早期检测计划CP结合 将编写计算CP风险的方法，以及（III）模拟 将用于确定将患者分配到 正常、中等和高风险类别。 该计划将 类似于PI开发的用于卵巢癌早期检测的方法， 具有标志物CA125的纵向水平的癌症。 长期 目标，超出本建议的范围，是扩大这些 早期检测CP的方法包括其他测试，如“免费” PSA”和直肠指检，以在软件中实现这些方法 适用于临床环境，并比较这种优化的 筛选策略与当前的筛选策略在一个随机 临床试验

DESCRIPTION (Applicant's Description) The goal of this pilot study is to develop an approach to early detection of carcinoma of the prostate (CP) that is optimized, i.e. that, when compared to the standard approach, results in the greatest increase in years of life saved for a given increment in testing. The principal investigator is currently developing precise statistical models of long term longitudinal PSA behavior using data from participants in the Veterans Affairs (VA) Normative Aging Study (NAS) as part of a currently funded study. After the distributional assumptions of these models have been tested, we will use them to develop an optimized early detection approach that reassesses the risk that the patient has prostate cancer after each successive PSA measurement based on all previous measurements. The decision for the next step, either biopsy or when to have the next PSA test, is based on the current assessment of risk. Those at elevated risk will be measured more frequently for PSA levels, and those at highest risk are referred for more invasive diagnostic workup such as biopsy. Thus, more screening resources are allocated to patients who are at increased risk. For the intermediate risk group, time until next PSA measurement will be optimized to maximize the expected years of life saved, using published estimates of treatment efficacy by stage and age. The approach will be developed in three stages: (I) A statistical method for estimating the risk of CP based on single or multiple longitudinal PSA levels, and the duration between the PSA levels will be developed, (II) A computer simulation of an early detection program for CP incorporating the method for calculating risk of CP will be written, and (III) The simulation will be used to identify the optimal scheme for assigning patients into normal, intermediate, and high risk categories. This program will be similar to an approach the PI has developed for early detection of ovarian cancer with longitudinal levels of the marker CA125. The long-term objectives, beyond the scope of this proposal, are to expand these approaches to early detection of CP to include other tests such as "free PSA" and digital rectal exam, to implement these approaches in software appropriate for use in clinical settings, and to compare such optimized screening strategies with current screening strategies in a randomized clinical trial.