By Krystle Seu, Dana Casciotti, PhD, Brandel France de Bravo, MPH, Mingxin Chen, MHS, and Nicholas Jury, PhD
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.1 One in every six men will be diagnosed with prostate cancer in his lifetime,2 with about 90% of cases occurring in men 55 and older, and 71% of deaths occurring in men 75 and older.3 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?
Diagnostic tests for prostate cancer are recommended for any man who has symptoms of prostate cancer, such as pain or changes in urination. Men over the age of 50 who have no symptoms sometimes undergo screening tests. In May 2012, the U.S. Preventive Services Task Force recommended against prostate-specific antigen (PSA) screening tests for men of any age. However, in May 2018, the Task Force revised their recommendation, stating that men ages 55-69 years old should talk to their doctor about the potential benefits and harms of PSA screening. The USPSTF continues to recommend against PSA screening in men age 70 and older. (see: https://screeningforprostatecancer.org)
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.4 5
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.6 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. However, it did not improve cancer detection.
What Recent Research Tells Us About Prostate Cancer Screening
Depending on how often screening is done, it may help reduce the chances of dying of prostate cancer, but the research indicates that the vast majority men with prostate cancer die of a different cause, even if they are not treated.
Two major research studies have tried to shed light on the value of regular screening: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the European Randomized Trial of Screening for Prostate Cancer. 7 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).8 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 death rates between the groups. Although the randomized portion of the study was completed in 2006, researchers are still studying the patients to see how long they live9.
The European study (ERSPC) included 182,000 men, ranging from 50 to 74 years old, from seven different European countries. 10 In these countries, “regular screening” is usually every 4 years, although it is every 2 years in Sweden. Those men were compared to men of the same age who did not get any prostate cancer screening. After the men were studied for an average of 13 years, the researchers found that the patients who had PSA screening were 27% less likely to die of prostate cancer. 11 However, they did not live longer than the other men, because they died of other causes.
Recent updates to a 2010 meta-analysis (which means researchers combined data from several 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 that men who were screened did not live longer than men who were not screened.12
A United Kingdom study published in 2018 in the prestigious medical journal JAMA involved over 160, 000 men between the ages of 50 to 59 years. The study found that a one-time PSA screen increased the chances of diagnosing prostate cancer, but did not change the chances of dying from prostate cancer. Over a 10-year period, about 4.3% of men who had a one-time PSA test were diagnosed with prostate cancer compared to about 3.6% of men who did not have a PSA screen. The one-time PSA screen was able to detect prostate cancers that were lower grade and less likely to be dangerous.
Importantly, there was no evidence that having a PSA screen test saved lives. In men who were diagnosed with prostate cancer, the chances of dying from the prostate cancer within 10-years of diagnosis were about 3 in 10,000 (less than half of a percent), and that was the case whether the men had a PSA screening or not. This means that a PSA may detect more prostate cancers, but these are likely cancers that would not have been harmful. The study does not show that one-time screening with PSA would be helpful, and it could be harmful. The researchers have planned to look at these issues more closely in a longer term study.13
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.
Unnecessary treatment costs a lot of money, but the main concern is the lack of evidence that it saves lives, on average, and the high rate of complications, which include serious and long-lasting problems, such as urinary incontinence and impotence.14
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.
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.15 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. That means it could have happened by chance.
In September 2016, the prestigious New England Journal of Medicine published a 10-year study by researchers from University of Oxford, which provided solid evidence that neither surgery nor radiation treatments save lives.16 The study compared the death rates of three patient groups: surgery, radiation, and active monitoring. Between 1999 and 2009, the study randomly assigned 1643 men with diagnosed prostate cancer to the three groups to receive radical surgery (553 men), radical radiotherapy (545), or active monitoring (545). Unlike the PIVOT study, patients in the “active monitoring group” underwent tests to determine if their prostate cancer had progressed; these were conducted every 3 months for the first year, and every 6 to 12 months after that. The patients had an average (median) of 10 years of follow-up.
At the final check-up, 169 men had died, and there was no significant difference among the three groups of prostate cancer patients. Only 17 of these were deaths from prostate cancer: 5 in the surgery group, 4 in the radiotherapy group, and 8 in the active-monitoring group. However, prostate cancer was more likely to progress or spread in the group of men who were monitored rather than treated.
This study was the first to compare the effectiveness of surgery, radiotherapy and active monitoring. The findings suggest that treatment does not improve the chances of a man living longer, since most of the men will be dying of other causes rather than prostate cancer. Since prostate cancer treatment can cause serious side effects such as erectile dysfunction and incontinence, active monitoring seems to be a reasonable option.