By Krystle Seu, Dana Casciotti, PhD, Brandel France de Bravo, MPH, Mingxin Chen, MHS, and Nicholas Jury, PhD
Although usually not fatal, prostate cancer is second leading cause of cancer deaths for men in the United States, after lung cancer. One in every eight men will be diagnosed with prostate cancer in his lifetime.1 Most cases are in men 65 and older, and most deaths occur in men 75 and older.2 Annual screenings would seem to be an important way to prevent prostate cancer. But there is a hot debate within the medical community: Do routine 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.3 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 ages 70 and older.4
What about other methods of screening, like digital rectal exams, which are usually done together with PSA testing? The Task Force continues to conclude that they tend to do more harm than good.
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 2008, the Task Force said screening was not recommended for men over 75, but wasn’t sure about its value for men younger than 75.5 In 2009, the American Urological Association issued new guidelines saying that annual screening was no longer recommended.6
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.7 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.
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 of 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 (ERSPC).8 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).9 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 live.10
The European study (ERSPC) included 182,000 men, ranging from 50 to 74 years old, from seven different European countries.11 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.8 However, they did not live longer than the other men, because they died of other causes.
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.12 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.13
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 (that’s 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 test may detect more prostate cancers, but these are likely cancers that would not have been harmful. This 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.14
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 it 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 complications, which include serious and long-lasting problems, such as urinary incontinence and impotence.15
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.16 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.17 The study compared the death rates of three patient groups: surgery, radiation, and active monitoring, which is sometimes called active surveillance. 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 is now recognized as a reasonable option. In fact, due to studies like this, active monitoring (also called active surveillance) is considered the preferred option for most men with low-risk prostate cancer.18 The number of men in the United States who receive active monitoring instead of active treatment has been increasing in recent years. In 2010, only 13% of men with prostate cancer received active monitoring, compared to 33% of men in 2015.
One small study found that high intensity exercise may be beneficial for men undergoing active monitoring. The study found that men who ran on a treadmill for 40 minutes, 3 times a week for 12 weeks had lower PSA levels after the 12 weeks than before they started the exercise regimen, but that was not true for men who did not do the exercise regimen. The researchers note that exercise increases cardiorespiratory fitness, which could inhibit the progression of prostate cancer for men on active monitoring.19
However, a 2020 study of over 80,000 men with low risk, localized prostate cancer found that active monitoring is not equally common across all regions of the United States and across all men.18 Men with Medicaid, as well as men living in counties where fewer residents have a college education, were less likely to receive active monitoring. Although rates of active monitoring were the same for Black and White men, the study found that Hispanic men were less likely to receive it. The researchers could not identify why this ethnic difference exists, but they suggested that it may be due to factors such as differences in how often the option is offered by doctors and patients’ preferences. The study also found that single men were more likely to use active monitoring than married men.
Since prostate cancer treatment can cause serious side effects such as erectile dysfunction and incontinence, active monitoring seems to be a reasonable option.
All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.
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- American Cancer Society. Key Statistics for Prostate Cancer. Cancer.org. https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html. Updated January 2021.
- National Cancer Institute. Cancer Stat Facts: Prostate Cancer. Seer.cancer.gov. https://seer.cancer.gov/statfacts/html/prost.html.
- Moyer VA. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Annals of Internal Medicine. 2012;157(2):120-34.
- Grossman DC, Curry SJ, Owens DK, Bibbins-Domingo K, Caughey AB, Davidson KW, Doubeni CA, Ebell M, Epling JW, Kemper AR, Krist AH. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018 May 8;319(18):1901-13.
- Calonge N, Petitti DB, Dewitt TG, Dietrich AJ, Gregory KD, Harris R, Isham GJ, Lefevre ML, Leipzig R, Loveland-Cherry C, Marion LN. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Annals of Internal Medicine. 2008; 149(3):185-91.
- Greene KL, Albertsen PC, Babaian RJ, Carter HB, Gann PH, Han M, Kuban DA, Sartor AO, Stanford JL, Zietman A, Carroll P. Prostate specific antigen best practice statement: 2009 update. The Journal of Urology. 2009; 182(5):2232-41.
- Vickers AJ, Till C, Tangen CM, Lilja H, Thompson IM. An empirical evaluation of guidelines on prostate-specific antigen velocity in prostate cancer detection. Journal of the National Cancer Institute. 2011; 103(6):462-9.
- Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Zappa M, Nelen V, Kwiatkowski M, Lujan M, Määttänen L, Lilja H, Denis LJ. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. The Lancet. 2014; 384(9959):2027-35.
- Andriole GL, Crawford ED, Grubb III RL, Buys SS, Chia D, Church TR, Fouad MN, Gelmann EP, Kvale PA, Reding DJ, Weissfeld JL. Mortality results from a randomized prostate-cancer screening trial. New England Journal of Medicine. 2009; 360(13):1310-9.
- National Cancer Institute. Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Prevention.cancer.gov. https://prevention.cancer.gov/major-programs/prostate-lung-colorectal-and-ovarian-cancer-screening-trial.
- Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ. Screening and prostate-cancer mortality in a randomized European study. New England Journal of Medicine. 2009; 360(13):1320-8.
- Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ. Prostate-cancer mortality at 11 years of follow-up. New England Journal of Medicine. 2012; 366(11):981-90.
- Djulbegovic M, Neuberger MM, Dahm P. Prostate-cancer mortality after PSA screening. The New England Journal of Medicine. 2012; 366(23):2228-9.
- Barry MJ. Screening for prostate cancer: is the third trial the charm?. JAMA. 2018; 319(9):868-9.
- Sanda MG, Dunn RL, Michalski J, Sandler HM, Northouse L, Hembroff L, Lin X, Greenfield TK, Litwin MS, Saigal CS, Mahadevan A. Quality of life and satisfaction with outcome among prostate-cancer survivors. New England Journal of Medicine. 2008; 358(12):1250-61.
- Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, Fox S, Gingrich JR, Wei JT, Gilhooly P, Grob BM, Nsouli I. Radical prostatectomy versus observation for localized prostate cancer. New England Journal of Medicine. 2012; 367:203-13.
- Hamdy FC, Donovan JL, Lane J, Mason M, Metcalfe C, Holding P, Davis M, Peters TJ, Turner EL, Martin RM, Oxley J. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. New England Journal of Medicine. 2016; 375:1415-24.
- Washington SL, Jeong CW, Lonergan PE, Herlemann A, Gomez SL, Carroll PR, Cooperberg MR. Regional Variation in Active Surveillance for Low-Risk Prostate Cancer in the US. JAMA Network Open. 2020; 3(12):e2031349-.
- Kang DW, Fairey AS, Boulé NG, Field CJ, Wharton SA, Courneya KS. Effects of exercise on cardiorespiratory fitness and biochemical progression in men with localized prostate cancer under active surveillance: the erase randomized clinical trial. JAMA Oncology. 2021 Oct 1;7(10):1487-95.