By Krystle Seu, Dana Casciotti, PhD, Brandel France de Bravo, MPH, and Danielle Pavliv
Prostate cancer is the #1 cancer in men and the second leading cause of cancer deaths for men in the United States, after lung cancer. One in every six men will be diagnosed with prostate cancer in his lifetime, with about 90% of cases occurring in men 55 and older, and 71% of deaths occurring in men 75 and older. For these reasons, annual screenings would seem to be an important way to prevent prostate cancer. But there is a hot debate within the medical community: do regular prostate cancer screenings do more harm than good?
Should I get screened?
In May 2012, the U.S. Preventive Services Task Force recommended against prostate-specific antigen (PSA) screening tests for men of any age if they do not have any symptoms of prostate cancer. The Task Force concluded that there is “moderate certainty that the benefits of PSA-based screening for prostate cancer do not outweigh the harms.”
What about other methods of screening, like digital rectal exams, which are usually done together with PSA testing? The Task Force also rejected those.
The U.S. Preventive Services Task Force is an independent group of medical professionals that reviews all evidence on preventive health care services. It adopted its current position after expressing doubts about the value of prostate cancer screening for several years. In 2009, the Task Force said screening was not recommended for men over 75, but wasn’t sure about its value for men younger than 75.” That same year, the American Urological Association issued new guidelines saying that annual screening was no longer recommended.
The reason why these experts concluded that screening was rarely necessary is that prostate cancer grows very slowly. Even without treatment, many men with prostate cancer will live with the disease until they eventually die of some other, unrelated cause.
Types of prostate cancer screening: PSA blood tests and digital rectal exams
Prostate cancer occurs when cells create small tumors in the prostate gland, which is an important part of the male reproductive system. Screening can be performed quickly and easily in a physician’s office using two tests: the prostate-specific-antigen (PSA) blood test, and the digital rectal exam (DRE), a manual exam of the prostate area.
Most screening tests are not 100% accurate, but these prostate tests are especially inaccurate. Most men with a high PSA level (>4ng/mL) do not have prostate cancer (this is known as a false positive), and some men with prostate cancer have a low PSA level (this is called a false negative). The DRE also results in many false positives and false negatives. Using both screening methods together will miss fewer cancers but also increases the number of false positives, which can lead to more testing (usually biopsies of the prostate) and possibly result in medical complications. A biopsy to determine if there is a cancerous growth in the prostate involves inserting a needle, usually through the rectum, to remove a small sample of prostate tissue.
Researchers are also trying to determine if other types of PSA testing might be more accurate in detecting prostate cancer, such as changes in PSA levels when a man has multiple tests over time. The rate of change of PSA level from one test to the next is known as “PSA velocity.”
One study examined if PSA velocity could improve cancer detection compared to standard PSA and DRE screening tests. Because men with high PSA levels and positive DRE results typically undergo prostate biopsies to determine the presence of cancer, this study evaluated if PSA velocity helped detect cancer in men with low PSA and negative DRE results. Over 5,500 men were included in the study and men with high PSA velocity-almost 1 in 7 men-were biopsied. The researchers found that doing biopsies on the basis of high PSA velocity in the absence of a high PSA or positive DRE would lead to a large number of biopsies but would not improve cancer detection.
Benefits and harms of screening
The benefit of screening is that the disease is often curable with early detection (90% or better). Common treatments like surgery or radiation aim to remove or kill all cancerous cells in the prostate. If the cancer spreads beyond the prostate before it is treated, it is often fatal. However, the cancer usually grows so slowly that is often equally safe to wait until there are symptoms before attempting to diagnose prostate cancer. Symptoms of prostate cancer might include urinary problems, difficulty having an erection, or blood in the urine or semen.
The harms of screening include 1) inaccurate results leading to unnecessary biopsies and complications, and 2) complications from unnecessary treatment. Even if a man has prostate cancer, if he does not have symptoms he may not need to be treated. Experts estimate that between 18% and 85% of prostate cancers detected by these screening tests would never become advanced enough to harm the patient. This wide range of uncertainty, however (is it less than 1 out of 5 or more than 4 out of 5?) just adds to the confusion.
Long before the Task Force made its recommendation, many doctors and patients questioned whether annual prostate cancer screenings were a good idea, since the disease is rarely fatal. Many also question whether treating early prostate cancer, the kind of prostate cancer screening tests mostly find, is a good idea. Treating early prostate cancer does not appear to help men live longer, and for many it drastically reduces their quality of life.
Doctors and scientists are searching for better tests for prostate cancer detection. Many experts believe that a family history of prostate cancer or other cancers should influence how often a man chooses to get PSA screening. However, the studies described below, which led to the Task Force’s recommendation against PSA screening, suggest that annual screenings for all men are not a good idea.
What recent research tells us about prostate cancer screening
In one study, screening (every four years) appeared to reduce prostate cancer deaths, but none of the studies showed improved survival: the men who were not screened lived just as long as those who were. The research supports what we already know: the vast majority men with prostate cancer die of a different cause.
Major research studies such as the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the European Randomized Trial of Screening for Prostate Cancer (ERSPC) have tried to shed light on the risks and benefits of regular screening. The PLCO studied 76,000 men, aged 55-74, for 7-10 years and found that the death rate from prostate cancer was low, and that it did not differ between the men who were screened every year for the first six years of the study and those who received their usual care (which ranged from no screening to occasional screening). For most of the patients, “usual care” included at least one screening during the first seven years of the study. There were also no significant differences in overall mortality between the groups.
The European study (ERSPC) included 182,000 men, ranging from 50 to 74 years old, from seven different European countries. After the men were studied for an average of 9 years, the researchers found that PSA screening every four years without DRE reduces prostate cancer deaths by about 20%. However, for each death prevented, the program needed to screen more than 1,400 men and treat an additional 48 men.7 Again, this study did not show differences in overall deaths between the screening and non-screening groups.
A follow-up to the ERSPC study, which tracked the men for an average of 11 years, found an even greater reduction in prostate cancer deaths-29% over the longer follow-up period. To prevent 1 death from prostate cancer, the program needed to screen 1,055 men and treat 37 men. More important, although deaths from prostate cancer were lower in the PSA screened group, there were no differences in overall mortality between the two groups. In other words, the PSA screening reduced deaths from prostate cancer but those men were more likely to die from other causes.
Recent updates to a 2010 meta-analysis (which means researchers “pooled” data from many different but comparable studies) of six randomized, controlled prostate cancer screening trials (including the PLCO and ERSPC studies) further support the U.S. Preventive Services Task Force recommendations. Analysis of data on almost 330,000 men showed no significant difference in the risk of death from prostate cancer between the men who received PSA screenings and those who did not.
A study published in 2011 by Swedish researcher Gabriel Sandblom and his colleagues followed men for 20 years to determine if screening for prostate cancer reduced deaths from prostate cancer. Investigators enrolled 9,026 men in Norrkoping, Sweden, aged 50-69 in 1987. They randomly chose 1,494 men to undergo screening every 3 years, using the DRE in 1987 and 1990 and DRE and PSA in 1993 and 1996. They were compared to 7,532 men who were not screened.
As of December 1999, 4% (292) of men in the control group and 6% (85) of men in the screening group were diagnosed with prostate cancer. Interestingly, among the 85 men diagnosed with cancer in the screened group, only about half of those cancers (43) were diagnosed at screening. The other 42 cancers were “interval cancers,” meaning they were diagnosed between screening appointments. The relatively small difference in diagnosis between the screened and non-screened groups, and the fact that only half of that difference (1%) was a result of screening, suggests that prostate cancer screening is not very effective. In addition, since prostate cancer grows slowly, many of those cancers could have been caught without screening before they were dangerous.
Did the men who were screened live longer as a result of screening? The researchers concluded that there was no significant difference in overall survival for men diagnosed with prostate cancer that were screened or not screened. Overall, 81% of men with prostate cancer in the screened group (69/85) and 86% of men with prostate cancer in the non-screened comparison group (252/292) died during the study period. About half of those men did not die of prostate cancer. Only 35% of men in the screened group (30/85) and 45% of men in the comparison group (130/292) died of prostate cancer. The difference was not statistically significant, which means the difference could be due to chance. However, if the 35% vs. 45% difference was maintained in a larger sample of men, that difference would have been statistically significant. Research using a much larger sample would be needed to determine if screening did make a significant difference in reducing deaths from prostate cancer. Based on this study, screening did not significantly reduce deaths from prostate cancer.
The study was stopped at the end of 1999, and unfortunately more recent follow-up data are not available.
Is surgery effective for men with early-stage prostate cancer?
When they hear the word “cancer,” many men want it treated immediately no matter how slow it is growing or how unlikely it is to be fatal. The question is: if found in its early stages, should prostate cancer be treated?
In July 2012, a study by researchers at the Department of Veterans Affairs was published in the New England Journal of Medicine, examining the effectiveness of surgery in men with early-stage prostate cancer. Known as the Prostate Cancer Intervention versus Observation Trial, or PIVOT, the study compared surgical removal of the prostate with no prostate cancer treatment. The 731 men who participated in the study, with an average age of 67, were randomly assigned to one of the two groups and followed for 8 to 15 years. All the men were enrolled between 1994 and 2002, with a final check-up taking place in 2010. Men in both groups went to the doctor every six months during the study, and men in the observation-only group were offered palliative therapy (which focuses on reducing suffering) or chemotherapy to relieve symptoms due to the cancer spreading to other parts of the body. Neither therapy can eliminate the cancer and, therefore, are not treatments.
The findings suggest that prostate cancer surgery does not save the lives of men with early-stage prostate cancer. Only 7% of the participants died of prostate cancer or from treatment during the study: 21 or 5.8% of those had their prostate removed and 31 (8.4%) who did not undergo surgery. The difference between the surgery and observation groups was not statistically significant, which means that the smaller number who died in the surgery group could have been due to chance. The prostate cancer spread to the bone in 4.7% of the surgery patients and to 10.6% of the observation or no-treatment group. Even when cause of death wasn’t limited to prostate cancer, the two groups died at about the same rate: 47% of the men who had surgery died during the study period as compared with 50% in the observation group.
The only men who benefited from the surgery were those with a PSA of 10 ng per milliliter or higher and men with riskier tumors: their overall risk of dying during the study period-not necessarily from prostate cancer-was lower than in the observation group. Surgery reduced the risk of dying from any cause by 13.2% among men with a PSA of 10 ng per milliliter or higher. For men with intermediate risk tumors (determined by a PSA value of 10.1 to 20.0 ng per milliliter, a score of 7 on the Gleason scale, or a stage T2b tumor), surgery reduced their risk of dying by 12.6%, but for men with high risk tumors, the reduction in risk by 6.7% was not statistically significant.
We agree with those who point out that the study is too small to make conclusions about the benefits of prostate surgery for men under 60, or men with advanced prostate cancer. However, the findings support the growing evidence that “active surveillance” is a reasonable option: why not delay the substantial risks of surgery until it seems truly necessary? While there are no studies comparing surgery and radiation therapy, they are believed to be equally effective and are known to have similar risks. Given the results of this study, some doctors and patients with early stage prostate cancer may decide that active surveillance is a reasonable alternative to radiation as well.
United States Cancer Statistics (2005). Center for Disease Control and Prevention. Retrieved on April 13, 2009 from: http://www.cdc.gov/Features/CancerStatistics/.
Prostate Cancer Foundation. Risk Factors. Retrieved on April 17, 2009 from: http://www.pcf.org/site/c.leJRIROrEpH/b.5802027/k.D271/Prostate_Cancer_Risk_Factors.htm
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