) 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.
| Whitehead, Kevin J; Plummer, Nicholas W; Adams, Jennifer A et al. (2004) Ccm1 is required for arterial morphogenesis: implications for the etiology of human cavernous malformations. Development 131:1437-48 |
