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From the Editor-in-Chief

Early-Stage Prostate Cancer: To Treat or Not To Treat

By William G. Nelson, MD, PhD

​Prostate cancer is a leading health problem for men. In 2014, there were an estimated 233,000 new prostate cancer cases and nearly 30,000 prostate cancer deaths in the U.S., with more than 300,000 prostate cancer deaths worldwide. Remarkably, this may be just the tip of the iceberg.

 
William G. Nelson, MD, PhD | Photo by Joe Rubino
The lifetime risk of a prostate cancer diagnosis for U.S. men is one in seven, with most prostate cancers discovered between ages 65 and 74. However, autopsy studies conducted by medical examiners of men not known to have prostate cancer suggest that the disease arises earlier and more commonly than these statistics suggest. In one study, pathologists looked through every nook and cranny of prostates recovered from autopsies for evidence of cancer. The findings were striking: Small prostate cancers were seen in as many as 29 percent of men between ages 30 and 40 and 64 percent between ages 60 and 70. Though only 1 in 38 men die of prostate cancer, more than two-thirds of men over age 70 carry cancer in their prostates, meaning many more men die with prostate cancer than of prostate cancer.
 
How can such cancers persist for decades and never cause symptoms or threaten life? Pathologists grade the potential aggressiveness of prostate cancer using the Gleason scale, in which 1 is least alarming and 5 is most menacing. It has become clear that low-grade prostate cancers (Gleason grades of 3 or less) grow slowly and rarely pose a health threat. In contrast, high-grade prostate cancers (Gleason grades 4 and 5) grow more rapidly, disseminate throughout the body and can lead to premature death. (A Gleason grade should not be confused with a Gleason score, which is the sum of two Gleason grades. A Gleason score of 6 or less indicates a low-grade prostate cancer, while scores of 8 to 10 point to a high-grade cancer.) The realization that low-grade prostate cancer acts so indolently has led some to argue that the greatest hazard of this condition may be complications from surgery, radiation therapy and hormonal treatments, therapies that can be lifesaving for higher-grade disease. The mystery of why low-grade and high-grade prostate cancers act so differently has not yet been solved.
 
Screening and early detection of prostate cancer using blood tests for prostate specific antigen (PSA) has been widespread in the U.S. since the early 1990s. These tests are responsible in part for the nearly 30 percent decline in prostate cancer deaths since then. Men discovered to have prostate cancer through biopsies triggered by an abnormal PSA test tend to have small tumors that are more readily treated and cured by surgery and radiation therapy. So for men with high-grade prostate cancers, treatment resulting from PSA screening offers significant benefits. However, treatment value is less clear for men diagnosed with low-grade prostate cancers. In a large randomized trial of PSA screening for prostate cancer, the screening resulted in a 21 percent reduction in prostate cancer deaths. However, 781 men needed to be screened and 27 men diagnosed through a biopsy to save one life. A worry that low-grade prostate cancers may be overtreated once they are discovered by PSA testing has led to controversy over the value of prostate cancer screening. The U.S. Preventive Services Task Force (USPSTF) now formally recommends against prostate cancer screening.
 
One answer to the conundrum of PSA screening and overtreatment may be greater use of active surveillance for small, low-grade prostate cancers diagnosed as a result of screening. The notion is that a man found to have only low-grade prostate cancer on a biopsy might be able to avoid treatment. Active surveillance mandates vigilant follow-up and requires frequent PSA testing and repeat biopsies. This helps ensure that high-grade prostate cancer, if missed by an earlier biopsy or if it appears in the future, can be discovered and treated. While some 25 to 50 percent of men with low-grade prostate cancer managed by active surveillance may ultimately need surgery or radiation therapy within 15 years, a little less than half of men with low-grade prostate cancer can expect to avoid treatment completely. Active surveillance appears to be a safe strategy, as less than 1 percent of men followed this way die 
of prostate cancer within 15 years.
 
As strategies for prostate cancer screening and active surveillance are refined, men may benefit from early detection and cure of life-threatening prostate cancer but avoid overtreatment of the non-life-threatening variety.

01/04/2016
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