ABSTRACT SCREENING PROSTATE SPECIFIC ANTIGEN EFFECTS ON RACIAL DISPARATE MORTALITY: A PROPENSITY SCORE ANALYSIS By R. David McNally, Ph.D., M.S.H.A. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2011 Dissertation Chair: Jeffrey S. Legg, Ph.D., Associate Professor and Chair, Doctoral Program in Health Related Sciences Department of Radiation Sciences Prostate cancer is the most commonly diagnosed cancer among men in the United States. It is frequently cited that racial disparities in mortality between Caucasian and African American men with localized prostate cancer exist. In addition, the question of whether prostate cancer screening with the prostate specific antigen blood test (PSA) leads to reduced mortality remains unanswered. Outcomes theory and survival analysis have shown controversial inconsistencies in support of early detection methods for prostate cancer to the extent that experts in the medical community do not agree on best-practice guidelines suggestive of eliminating such disparities and reducing mortality. The purpose of this study was to explore the relationship between screening PSA tests and racial differences in mortality among Caucasian and African American men with application of a propensity scoring analysis on a large population-based data set. Prostate cancer patients diagnosed from January 1, 1986 through December 31, 2006 (n = 515,802 cases) from the SEER-17 data set linked to Medicare claims files were included. A separate analysis using a 5% randomized group of over 263,000 men without prostate cancer was also examined. The results demonstrated that no statistically significant differences in mortality between Caucasians and African Americans in the prostate cancer group existed (p=0.993). Further, the same result was found among men from the 5% randomized group without prostate cancer (p= 0.832), that no statistically significant difference exists for this study population when using a propensity scoring analysis and a conditional Cox regression model. From both analyses, no survival benefit was found for screened men versus non-screened men when using the PSA test for early detection. In addition, because age is a well-known predictor of death, a separate analysis was performed on age-matched men. The results for the age analysis also demonstrated no statistically significant differences in racial mortality or whether screening PSA reduced mortality after applying a propensity scoring analysis to a conditional Cox regression model. In conclusion, it is believed that using a propensity scoring method and Cox regression analysis improved the evaluation of this large population data set where censoring for survival time was important and where matched pairs were utilized. Further work in health services research using large population-based data sets should be pursued and incorporating Cox regression with a propensity analysis can be helpful.

Prostate adenocarcinoma (PCa) is one of the most prevalent cancers in the world. Second only to lung cancer, the key to its successful treatment is in its early detection. With the introduction of prostate-specific antigen in the early 1990s, a screening test involving measuring levels of this protein was developed to detect PCa in asymptomatic individuals. This test is also known as the PSA test. PCa-specific mortalities have been in decline since the test's introduction. Despite this decline, recent studies have called the efficacy of the PSA test into question. Two large randomized controlled trials conducted in the US and Europe reveal contradicting results as to PSA's accuracy and usefulness. Concerns of overdiagnosis and overtreatment as the result of using PSA screening has led to many national organizations recommending caution or even recommending against its use. Through a thorough review of a large collection of current PCa literature, this study reviews the flaws of using PSA to screen for PCa and investigates alternative approaches currently being pursued through active research to make PCa early detection more accurate. These approaches include improving the accuracy of the PSA screen using PSA-derived testing methods, using PCa-induced epigenetic modifications as a new target for PCa screening, and using urine biomarkers. All of these methods were compared using area under the curve (AUC) values obtained via receiver operating characteristic analysis. Each method has its own flaws but by comparing each of the different approaches, I was able to conclude that out of the currently available screening methods, screening for Engrailed-2 protein in urine is the most promising screening method with the highest AUC values compared to the other methods. Although this method has been introduced in the UK, it has not been introduced in the US yet. Epigenetic screening methods hold the most promise for accurate PCa screening in the future as it confers the highest accuracy in detecting PCa. However, as it hasn't been shown that epigenetic modifications can be easily obtained in the urine or blood serum for easy and accurate screening, I believe more work has to be done in order for it to be successful in being applied as a screening test. By determining the most promising screening type, we can focus resources and efforts towards finding a way to detect PCa early, allowing for successful treatment.