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INTRODUCTION

Identifying healthy, asymptomatic individuals harboring occult cancer before it becomes symptomatic intuitively makes sense, assuming that disease progresses in a linear fashion; at first silent and later progressing through states of increasing abnormality, until it becomes symptomatic and, eventually, lethal. In 1907, Dr. Charles Childe published his book, The Control of a Scourge, Or, How Cancer Is Curable. His argument was that the mortality associated with cancer was related to its late presentation: “Cancer itself is not incurable … it is the delay that makes it so.” This thesis informed the inception of cancer screening in the medical community and, with it, the aspiration of finding disease at an earlier stage when intervention may be curative, or at least curtail morbidity.

Prostate cancer is common. In the United States today, 13% of men have a lifetime risk of being diagnosed with prostate cancer and a 2.5% lifetime risk of dying from this disease.1 There are approximately 30,000 deaths each year that can be attributed to prostate cancer, making it the second most common cause of cancer-related death among men in the United States.1 Since 1975, the epidemiology of prostate cancer has changed significantly, partly as a consequence of population-based screening aided by measuring prostate-specific antigen (PSA) in the serum.

Since the introduction of PSA screening in the early 1990s, we have observed both a marked increase in the incidence of prostate cancer and an unprecedented stage migration, with more than 91% of patients diagnosed with prostate cancer today presenting with localized disease. Prior to PSA screening, only the digital rectal exam was available for screening and 1 out of 5 individuals presented with bone metastases.2

In the last 2 decades, we have also observed a significant decrease in the prostate cancer mortality rate among men in the United States, from 31.6 per 100,000 men in 1999 to 18.9 per 100,000 men in 2015.1 Prostate cancer death has fallen a total of 47% in the United States from its peak incidence rate. This is likely explained both by improvements in the available treatments for local and advanced prostate cancer and by PSA screening and early detection.

The natural history of prostate cancer is not the same for all men. Whereas some men with high-grade cancers develop aggressive disease that can lead to death, many others will die of unrelated causes with indolent disease that would have been of no consequence if never discovered.3 Jahn et al. reviewed 19 studies of prostate cancer discovered at autopsy. This included a review of 6024 men who died of other causes. They observed that among men age 70 to 79, 36% of Caucasians and 51% of African Americans had occult disease.4 Sakr et al. analyzed an autopsy cohort of men under 50 years of age who died of unrelated causes and observed 27% of young men in their ...

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