Overdiagnosis of Prostate Cancer

This chapter addresses issues relevant to prostate cancer overdiagnosis. Factors promoting the overdiagnosis of prostate cancer are reviewed. First is the existence of a relatively large, silent reservoir of this disease, as can be seen by evaluating autopsy studies and histologic step-sectioning results of prostates removed for other causes. The second main factor responsible for prostate cancer overdiagnosis is fairly widespread prostate-specific antigen and digital rectal examination-based screening, which has been fairly widely practiced in the United States for the past 20 years among heterogeneous groups of men. This has resulted in the identification of many men from this reservoir who otherwise may never have been diagnosed with symptomatic prostate cancer and is substantially responsible for the current annual incidence to mortality ratio for prostate cancer of approximately 6 to 1. Finally, the relatively indolent natural history and limited cancer-specific mortality as reported in a variety of contemporary randomized screening and treatment trials is reviewed. We attempt to quantitate the proportion of newly diagnosed prostate cancers that are overdiagnosed using various trial results and models. We explore the impact of prostate cancer overdiagnosis in terms of patient anxiety and the potential for overtreatment, with its attendant morbidity. We explore strategies to minimize overdiagnosis by targeting screening and biopsy only to men at high risk for aggressive prostate cancer and by considering the use of agents such as 5-alpha reductase inhibitors. Future prospects to prevent overtreatment, including better biopsy and molecular characterization of newly diagnosed cancer and the role of active surveillance, are discussed.