Prostate cancer screening

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Prostate cancer screening
Medical diagnostics

Prostate cancer screening is an attempt to identify individuals with prostate cancer in a broad segment of the population—those for whom there is no reason to suspect prostate cancer.[1] There are currently two methods used: One is the digital rectal examination (DRE), in which the examiner inserts a gloved, lubricated finger into the rectum to examine the adjoining prostate. The other is the prostate-specific antigen (PSA) blood test, which measures the concentration of this molecule in the blood.[2]

Informed decision making is recommended when it comes to screening.[3] The United States Preventive Services Task Force recommends against routine screening using the PSA test, due to the risk of overdiagnosis and overtreatment, as most cancer diagnosed would remain asymptomatic.[4] Others recommend screening people with a PSA test or DRE who are at high risk and have a long life expectancy.[5] Potential benefits of screening stem from early detection; decreasing rates prostate-cancer specific mortality and metastatic disease, and increasing detection of localized cancers (better prognosis).[6]

Guidelines from the American Urological Association,[7] and the American Cancer Society[8] recommend that men be informed of the risks and benefits of screening. The American Society of Clinical Oncology recommends screening be discouraged in those who are expected to live less than ten years, while in those with a life expectancy of greater than ten years a decision should be made by the person in question based on the potential risks and benefits. In general, they conclude that based on recent research, "it is uncertain whether the benefits associated with PSA testing for prostate cancer screening are worth the harms associated with screening and subsequent unnecessary treatment." [9]

Controversy about screening[edit]

Prostate cancer can develop into a fatal, painful disease, but it can also develop so slowly that it will never cause problems during the man's lifetime.[1] It is difficult for a physician to determine how the cancer will proceed based on screening tests currently available alone.[1]

The United States Preventive Services Task Force (USPSTF) recommended against PSA screening in healthy men finding that the potential risks outweigh the potential benefits.[10] This October 2011 recommendation is based on a review of evidence and concludes that "prostate-specific antigen–based screening results in small or no reduction in prostate cancer–specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary."[11]

Hal Arkes presents the statistical case as follows:

If there were two auditoriums each filled with 1,000 men, one filled with men who had taken PSA screening tests and the other with men who didn't take the test, there would be just as many men (8) "who died of prostate cancer in each auditorium, which leads us to think in the aggregate it didn't do any good." Among those who took the test there would also be 20 men who were treated for prostate cancers which never would have caused symptoms. Five of these men would have lifelong complications, including impotence and incontinence.[12][13]

This recommendation has been criticized by many prostate cancer experts for an over-reliance on findings of the U.S. Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.[14] This trial intended to randomize men between screening and no screening. However, because the study was initiated during a time when PSA screening was already becoming widely adopted, there were high rates of PSA testing among men who were in the control arm. This rate of "contamination" was very high: acknowledged by the authors to be 44% before the study started and 52% during the course of study. In fact, the rate was likely much higher, since over 90% of the prostate cancers found in the "control" arm were stage T1 or T2, which by definition can only be detected with screening.[15] The PLCO authors stated in a later publication that the PLCO should not be interpreted as a trial of screening vs. no screening, but rather as a trial of annual screening vs. so-called opportunistic or ad-hoc screening.[16] The USPSTF also based their assessment of the "harms" of screening and treatment based on a biased and out-dated literature review. For just one example, their statement cited a 1:200 risk of dying within 30 days of radical prostatectomy. This number comes from men over the age of 65 treated in the early 1990s; the actual number in contemporary practice is closer to 1:10,000.[17]

PSA testing of men in their mid-70s and older, is discouraged as most people at this age diagnosed with prostate cancer detected by a PSA test would die of other causes before the cancer caused problems.[18] On the other hand, up to 25% of men diagnosed in their 70s or even 80s die of prostate cancer, if they have high-grade (i.e., aggressive) prostate cancer.[19] Conversely, some argue against PSA testing for men who are too young, because too many men would have to be screened to find one cancer, and too many men would have treatment for cancer that would not progress. This argument again ignores the fact that low-risk prostate cancer does not require immediate treatment, but may be amenable to active surveillance.[20]

Prostate cancer is a common (by far the most common) solid-organ cancer diagnosed among men and surpassed only by lung cancer as a source of cancer mortality[21]). Prostate cancer is also extremely heterogeneous: many, perhaps most, prostate cancers are indolent and would never progress to a clinically meaningful stage if left undiagnosed and untreated during a man's lifetime. On the other hand, a subset are potentially lethal, and screening can identify some of these within a window of opportunity for cure[22] Thus the concept of PSA screening is advocated by some[23] as a means of detecting high-risk, potentially lethal prostate cancer, with the understanding that lower-risk disease, if discovered, often does not need treatment and may be amenable to active surveillance.[24]

Screening for prostate cancer is controversial because of cost and uncertain long-term benefits to patients.[25][26] Testing may lead to overdiagnosis and unnecessary treatment. Follow-up tests can include painful biopsies which can result in excessive bleeding and infection. The discoverer of PSA, Dr. Richard J. Ablin, concludes that the test's popularity "has led to a hugely expensive public health disaster," as only 16 percent of men will ever receive a diagnosis of prostate cancer, but only a 3 percent chance of dying from it. He states that "the test is hardly more effective than a coin toss."[27] Dr. Horan echos that sentiment in his book.[28]

According to the American Urological Association, the controversy over prostate cancer should not surround the test, but rather how test results influence the decision to treat:

"The decision to proceed to prostate biopsy should be based not only on elevated PSA and/or abnormal DRE results, but should take into account multiple factors including free and total PSA, patient age, PSA velocity, PSA density, family history, ethnicity, prior biopsy history and comorbidities.
"A cancer cannot be treated if it is not detected. Not all prostate cancers require immediate treatment; active surveillance, in lieu of immediate treatment, is an option that should be considered for some men. Testing empowers patients and their urologists with the information to make an informed decision."[29]

Private medical institutes, such as the Mayo Clinic, likewise acknowledge that "organizations vary in their recommendations about who should — and who shouldn't — get a PSA screening test." They conclude: "Ultimately, whether you should have a PSA test is something you'll have to decide after discussing it with your doctor, considering your risk factors and weighing your personal preferences."[30]

A study in Europe resulted in only a small decline in death rates and concluded that 48 men would need to be treated to save one life. But of the 47 men who were treated, most would be unable to ever again function sexually and require more frequent trips to the bathroom.[27][28]

A study published in the New England Journal of Medicine found that over a 7 to 10-year period, "screening did not reduce the death rate in men 55 and over."[27][28] Former screening proponents, including some from Stanford University, have come out against routine testing. In February 2010, the American Cancer Society urged "more caution in using the test." And the American College of Preventive Medicine concluded that "there was insufficient evidence to recommend routine screening."[27][28]


The annual cost of PSA screening in the U.S. totals at least $3 billion, with much of it paid for by Medicare and the Veterans Administration.

According to Ablin, "testing should absolutely not be deployed to screen the entire population of men over the age of 50 . . ." He concludes that the primary promoters of tests are drug companies, which "continue peddling the tests," along with advocacy groups including the American Urological Association, all of which "stand to profit" by pushing continual tests. He states:

"I never dreamed that my discovery four decades ago would lead to such a profit-driven public health disaster. The medical community must confront reality and stop the inappropriate use of P.S.A. screening. Doing so would save billions of dollars and rescue millions of men from unnecessary, debilitating treatments."[27][28]

Ablin has also written: “it is prudent only to use a single PSA determination as a baseline, with biopsy and cancer treatment reserved for those with significant PSA changes over time, or for those with clinical manifestations mandating immediate therapy..... absolute levels of PSA are rarely meaningful; it is the relative change in PSA levels over time that provides insight, but not definitive proof of a cancerous condition necessitating therapy.“.[31]

Clinical practice guidelines[edit]

Clinical practice guidelines for prostate cancer screening are controversial because the benefits of screening may not outweigh the risks of follow-up diagnostic tests and cancer treatments:[32]

  • The United States Preventive Services Task Force (USPSTF) recommended against PSA screening in healthy men in October 2011 finding that the potential risks outweigh the potential benefits.[10] This recommendation, released in October 2011, is based on a review of evidence and concludes that "prostate-specific antigen–based screening results in small or no reduction in prostate cancer–specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary."[11]
  • American Cancer Society, in its cancer screening guidelines says that it does not support routine screening for prostate cancer.[33] This is because the benefits are unclear or unproven.[34] Instead it recommends that doctors discuss the pros and cons of testing and that men should be offered the possibility of a DRE and a PSA test if they are over 50 with a life expectancy of more than 10 years (or over 40 if they are in a high-risk group). It recommends that men should sit down with their physician and weigh the benefits and risks of the test before a decision is made.[33] Men at high risk for prostate cancer such as African-American men should discuss this with their doctor at age 45. Men who have a first-degree relative (father, brother, or son) diagnosed with prostate cancer at an early age (younger than age 65) and men with several first-degree relatives diagnosed at an early age should begin the discussion at age 40.[35]

The American Urological Association said in early 2009 that "The decision to screen is one that a man should make in conjunction with his physician, and should incorporate known prostate cancer risk factors, such as family history of prostate cancer, age, ethnicity/race, and whether or not a man has had a previous negative prostate biopsy. These factors are different for every man and, therefore, the benefits of screening should be considered in the broader perspective."[36] The organization will review its best practice guidelines later in 2009.

  • The 2008 recommendations of the U.S. Preventive Services Task Force (USPSTF) concluded that routine screening for prostate cancer using PSA testing or digital rectal examination (DRE) was not recommended for men over 75 and that the evidence was insufficient to recommend for or against screening for men under 75 years old.[37] The previous 1995 USPSTF recommendation was against routine screening.
  • The American Cancer Society (ACS) has recently updated its guidelines making clear that it does not recommend routine prostate cancer screening for all men.[38] It recommends that the risks and benefits of screening need to be weighed, and discussions should start early for those in high-risk groups. Screening should take place only wíth informed consent of the patient in full knowledge of both benefits and risks. The revised guidelines reflect the concerns about the potentially down-played risks and over-blown claims for the success of prostate cancer screening.[39][40]
The American Cancer Society (ACS) does not support routine testing for prostate cancer at this time. ACS does believe that health care professionals should discuss the potential benefits and limitations of prostate cancer early detection testing with men before any testing begins. This discussion should include an offer for testing with the prostate-specific antigen (PSA) blood test and digital rectal exam (DRE) yearly, beginning at age 50, to men who are at average risk of prostate cancer and have at least a 10-year life expectancy. Following this discussion, those men who favor testing should be tested. Men should actively take part in this decision by learning about prostate cancer and the pros and cons of early detection and treatment of prostate cancer. This discussion should take place starting at age 45 for men at high risk of developing prostate cancer. This includes African American men and men who have a first-degree relative (father, brother, or son) diagnosed with prostate cancer at an early age (younger than age 65). This discussion should take place at age 40 for men at even higher risk (those with several first-degree relatives who had prostate cancer at an early age). If, after this discussion, a man asks his health care professional to make the decision for him, he should be tested (unless there is a specific reason not to test). [38]
  • Some U.S. radiation oncologists and medical oncologists who specialize in treating prostate cancer recommend obtaining a baseline PSA in all men at age 35[41] or beginning annual PSA testing in high risk men at age 35.[42]
  • The American Urological Association Patient Guide to Prostate Cancer.[43]

Since there is no general agreement that the benefits of PSA screening outweigh the harms, the consensus is that clinicians use a process of shared decision-making that includes discussing with patients the risks of prostate cancer, the potential benefits and harms of screening, and involving the patients in the decision.[44]

As of 2015 the UK National Health Service did not offer PSA screening, on the basis that it is not reliable.[45]


In the European Randomized Study of Screening for Prostate Cancer (ERSPC) initiated in the early 1990s, the intention was to evaluate the effect of screening with prostate-specific antigen (PSA) testing on death rates from prostate cancer. The trial involved 182,000 men between the ages of 50 and 74 years in seven European countries randomly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening. During a median follow-up of almost 9 years, the cumulative detected incidence of prostate cancer was 820 per 10,000 in the screening group and 480 per 10,000 in the control group. Deaths from these cancers in this time was much lower. There were 214 prostate cancer deaths in the screening group and 326 in the control group, a difference of 7.1 men per 10,000 in the tested group compared to the control. The researchers concluded that PSA-based screening did reduce the rate of death from prostate cancer by 20%, but that this was associated with a high risk of overdiagnosis, which means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent just one death from prostate cancer within 9 years. However, the number needed to treat to prevent one progression to metastatic disease was only 24, and both numbers are expected to fall as patients in the study are followed for longer periods of time.[46] Furthermore, the benefit for screening was greater (30% rather than 20%) with adjustment for noncompliance and contamination (i.e., men who were randomized to get PSA tests but did not, and those who were in the control arm but actually received PSA tests during the study period).[47] One recent analysis of the ERSPC data suggested that projecting over a 25-year time horizon, which is more appropriate for a man in his 50s than the 9 years reported to date from the trial, the number needed to screen falls to 186-220, and the number needed to treat to prevent a death falls to between 2 and 5 men.[48]

In addition to the 20 percent reduction in prostate cancer mortality shown by the ERSPC study, a more recent study has shown greater effectiveness in how screening has reduced the prostate cancer death rate. A study published in the European Journal of Cancer (October 2009) documented that prostate cancer screening reduced prostate cancer mortality by 37 percent. By utilizing a control group of men from Northern Ireland, where PSA screening is infrequent, the research showed this substantial reduction in prostate cancer deaths when compared to men who were PSA tested as part of the ERSPC study.[49]

The results from two of the largest randomized trials have now been published.[50]

A US study, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial,[51] looked at the general effectiveness of a screening program involving both PSA and DRE methods. This was conducted between 1993 thu 2001, in which 76,693 men at 10 U.S. study centers 38,343 subjects received screening (an annual PSA testing for 6 years and DRE for 4 years) and a control group of 38,350 subjects received 'usual care' with subjects and health care providers receiving the results and deciding on the type of follow-up evaluation. 'Usual care' means that some in this group would have received some screening, as some organizations have recommended. After 7 years of follow-up, the incidence of prostate cancer per 10,000 person-years was 116 (2,820 cancers) in the screening group and 95 (2,322 cancers) in the control group. The incidence of death attributed to prostate cancer per 10,000 person-years was 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the control group (rate ratio, 1.13; 95% CI, 0.75 to 1.70). The data at 10 years were 67% complete and consistent with these overall findings. The researchers concluded that after 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups.[51]

Commenting on the findings, the Chief Medical Officer of the American Cancer Society, Otis W. Brawley, MD, said

"Many experts had anticipated these studies would show a small number of men will benefit from prostate screening, but a large number of men will be treated unnecessarily. And that's what these studies show. However, the question is not as simple as: 'does prostate cancer screening work?' What we need to know is: what are benefits of prostate cancer screening and are they large enough to outweigh the harms associated with it? And despite the release of this early data, we still cannot say whether the benefits outweigh the risk.[35]"

His Deputy chief medical officer, Len Lichtenfeld, MD, MACP said

"When one considers all of the problems associated with treatment for prostate cancer -- urine incontinence, impotence, pain and bleeding among others -- that is a lot of men left with a lot of symptoms to save one life."

A further study, the NHS Comparison Arm for ProtecT (CAP) and Prostate testing for cancer and Treatment (ProtecT) studies randomized GP practices with 460,000 men aged 50–69 at centers in 9 cities in Britain from 2001-2005 to usual care or prostate cancer screening with PSA (biopsy if PSA ≥ 3),[52] has yet to report.

Alternative techniques[edit]

Given the high false-positive rate of the PSA test, research into the use of economically efficient novel biomarkers with greater sensitivity and specificity is ongoing. The goal is early identification of men harboring potentially fatal disease who should be referred for biopsy. Given that no single biomarker has yet been identified, combinations of biomarkers and clinical factors are being studied.

For example, The Stockholm 3 (STHLM3) study utilized a blood test to obtain plasma protein biomarkers (PSA, free PSA, intact PSA, hK2, MSMB, MIC1), and genetic polymorphisms (232 SNPs). These results were added to patient clinical factors (age, family history, previous negative prostate biopsy, prostate exam) and PSA concentration with the goal of increasing specificity without diminishing sensitivity to high-risk prostate cancer. The STHLM3 model performed significantly better than PSA alone in identifying cancers with a Gleason score of at least 7 and is estimated to reduce the number of biopsies by 32% and avoid 44% of negative biopsies.[53]

The PCA3 urine test, which is obtained from the first portion of a urine sample following a prostate massage and digital rectal exam, has been shown to correlate significantly higher with positive biopsies than PSA. With a PCA3 score cut-off of 35, sensitivity was 68%, specificity 71%, positive predictive value 67% and negative predictive value 71%. Overall accuracy was 69%. However, the score correlates better with tumor volume than tumor aggressiveness.[54]

An alternative model to biomarkers utilizes pre-biopsy multiparametric magnetic resonance imaging (mpMRI) of the prostate with patients whose PSA is suspicious for cancer. The noninvasive mpMRI scan detects significant prostate cancer with up to 97% accuracy and allows the targeting of biopsy needles into the region of interest. This model potentially minimizes unnecessary prostate biopsies while maximizing biopsy yield.[55] Despite concerns about the cost of MRI scans, compared to the long-term cost burden of the PSA/TRUS biopsy-based standard of care, the imaging model has been found to be cost-effective.[56]

Transrectal ultrasonography (TRUS) has the advantage of being fast with minimal invasive and better than MRI for the evaluation of superficial tumor. It also gives details about the layers of the rectal wall, accurate and useful for staging primary rectal cancer. While MRI is better in visualization of locally advanced and stenosing cancers. For staging perirectal lymph nodes, both TRUS and MRI are capable. TRUS has small field of view, but 3D TRUS can improve the diagnosis of anorectal diseases.[57]


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