PSA Level During Midlife and Undiagnosed Prostate Cancer at Autopsy: Understanding Tumor Biology and Racial Disparities
Abstract
Prostate specific antigen (PSA) screening has been shown to reduce deaths from prostate cancer by detecting cancer at an early stage before it becomes symptomatic for the patient. However, prostate cancer is very common, and most men with the disease will not die from prostate cancer, but from something else. As a result, the use of PSA screening has been controversial due to the real risk of overdiagnosis and overtreatment of men with tumors that would never have become symptomatic or led to death. In addition, due to inadequate research efforts, it is not well known how best to screen for prostate cancer in black men, despite their being at a higher risk of developing and dying of prostate cancer than white men. One strategy for improving PSA screening is to do an earlier measurement of PSA during midlife (aged 40-55). PSA levels during midlife have been shown by our group and others to strongly predict long-term risk of prostate cancer, particularly risk of aggressive disease, in both black and white men. This could be used to determine which men should undergo more intensive ongoing screening and which men could safely be screened less frequently. As a result, much of the benefit of PSA screening on prostate cancer mortality could be maintained, while overdiagnosis and overtreatment would be reduced. What remains unclear is why PSA during midlife predicts so well for future aggressive prostate cancer. We hypothesize that PSA levels are elevated due to the presence of very early, undiagnosed tumors, some of which may have the potential to become aggressive decades later. Previous autopsy studies of men who died of other causes have shown that prostate cancer starts very early in adulthood, a finding even more pronounced in African-American men. Nearly a third of African-American men harbor latent prostate cancer in their 30s and 40s. Previous autopsy studies have not connected PSA levels at the time of autopsy to the presence of undiagnosed prostate cancer at the time of death. In this study, we aim to connect PSA levels in midlife with the presence of early, undiagnosed tumors for the first time. This autopsy study connecting PSA levels and undiagnosed tumors at the time of death among black and white men who died of causes other than prostate cancer will develop the evidence for a smarter, targeted PSA screening strategy based on a PSA level in midlife. We will conduct an autopsy study among 300 black and white men aged 30-59 in Boston and Chicago to assess how PSA in midlife relates to the pre-diagnosis natural history of prostate cancer. We will also study whether adding other blood markers may provide additional predictive benefit over a simple PSA measurement in predicting aggressive prostate cancer. Finally, we will use known variations in genes that influence PSA level or risk of prostate cancer to create a personalized risk score to determine whether prediction for cancer can be improved even further. Overall, we believe these results will contribute valuable evidence to the creation of improved screening guidelines for both black and white men. It is projected to take approximately 3 years for the study to be completed and results to be available for the public. Findings will then be used to influence development and use of PSA screening guidelines for doctors and patients in order to diagnose aggressive prostate cancer in black and white men in time for it to be treated and, hopefully, cured. Furthermore, men at low risk for aggressive prostate cancer will be able to avoid frequent screenings and unnecessary biopsies with the complications that accompany them. We believe that our results will help physicians and their patients make more informed decisions about prostate cancer screening immediately. In the longer term, our results may support the development of randomized trials of screening to inform the development of national guidelines. We hope that smarter, more targeted prost
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910708
Entities
People
- Mark Preston
Organizations
- Brigham and Women's Hospital
- United States Army