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  • Guideline Synthesis

Screening for Prostate Cancer

Guidelines Being Compared:

  • American College of Physicians (ACP)

    Screening for prostate cancer: a guidance statement from the Clinical Guidelines Committee of the American College of Physicians.

    2013 Apr 01

    View Summary

  • American Urological Association Education and Research, Inc. (Am Urol Assoc Edu Res)

    Early detection of prostate cancer: AUA guideline.

    2013 Apr 01

    View Summary

  • U.S. Preventive Services Task Force (USPSTF)

    Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement.

    2012 May 22

    View Summary

A direct comparison of the recommendations presented in the above guidelines for prostate cancer screening is provided in the tables. The ACP guidance statement was developed from an appraisal of guidelines developed by other organizations on screening for prostate cancer. Additional details of this process are available in the Methodology section of this synthesis.

Areas of Agreement

None of the guideline developers recommends routinely screening for prostate cancer using the PSA test in any age group. The groups agree that PSA-based prostate cancer screening should not occur in the absence of an informed, shared decision-making process, and that the decision to initiate or continue PSA screening should reflect an explicit understanding of the possible benefits and harms, as well as patients' preferences and values.

Areas of Difference

Screening in Average-Risk, Asymptomatic Men

ACP and AUA take similar approaches to providing screening recommendations, with both providing guidance according to patient age. However, the age ranges for which screening is either not routinely recommended or explicitly recommended against differ somewhat. ACP recommends against PSA screening in average-risk men under the age of 50 years, men over the age of 69 years, or men with a life expectancy of less than 10 to 15 years. The developer recommends that clinicians inform men between the ages of 50 and 69 years about the limited potential benefits and substantial harms of screening for prostate cancer, and that clinicians base the decision to screen for prostate cancer using the PSA test on the risk for prostate cancer, a discussion of the benefits and harms of screening, the patient's general health and life expectancy, and patient preferences. ACP further recommends that clinicians should not screen for prostate cancer using the PSA test in men who do not wish to make the screening decision or do not express a clear preference for screening.

AUA also provides recommendations for screening according to age. The developer explicitly recommends against PSA screening in men under age 40 years, and does not recommend routine PSA screening in average-risk men aged 40 to 54, men aged 70 or older, or any man with a less than 10 to 15 year life expectancy. For men ages 55 to 69 years who are considering PSA screening, AUA strongly recommends shared decision-making, and proceeding based on men's values and preferences. In those men who have participated in shared decision-making and have decided on screening, AUA states that a routine screening interval of two years or more may be preferred over annual screening. As compared to annual screening, AUA continues, it is expected that screening intervals of two years preserve the majority of the benefits and reduce overdiagnosis and false positives. According to AUA, the guideline panel did not interpret the evidence from a public health perspective but rather from the perspective of the individual, with emphasis on the information—both benefit and harm—that an asymptomatic man would need to make an informed decision about prostate cancer screening.

The USPSTF explicitly recommends against PSA-based screening for prostate cancer in all average-risk men, regardless of age. The primary goal of PSA-based screening is to find men for whom treatment would reduce morbidity and mortality. According to the USPSTF, studies demonstrate that the number of men who experience this benefit is, at most, very small, and PSA-based screening as currently implemented in the United States produces more harms than benefits in the screened population.

With regard to implementation of this recommendation, the USPSTF recognizes the use of PSA screening is common practice and understands that some men will continue to request it and some physicians will continue to offer it. The decision to initiate or continue PSA screening, USPSTF notes, should reflect an explicit understanding of the possible benefits and harms and respect the patients' preferences. Physicians should therefore not offer or order PSA screening unless they are prepared to engage in shared decision making that enables an informed choice by the patients. Similarly, patients requesting PSA screening should be provided with the opportunity to make informed choices that reflect their values.

Screening for Prostate Cancer

ACP
(2013)

Guidance Statement 1: ACP recommends that clinicians inform men between the age of 50 and 69 years about the limited potential benefits and substantial harms of screening for prostate cancer. ACP recommends that clinicians base the decision to screen for prostate cancer using the PSA test on the risk for prostate cancer, a discussion of the benefits and harms of screening, the patient's general health and life expectancy, and patient preferences. ACP recommends that clinicians should not screen for prostate cancer using the PSA test in patients who do not express a clear preference for screening.

Benefits and Harms of Screening (PSA Test and DRE)

The modest potential mortality benefit in 1 prostate cancer screening trial with the PSA test was limited to men between the age of 55 and 69 years. Data were insufficient to reach a conclusion about the benefits or harms of screening in men aged 50 to 54 years. However, because this group has a longer life expectancy, they have more potential for long-term net benefit. The European Randomized Study of Screening for Prostate Cancer (ERSPC) study, which screened men mostly with the PSA test, showed that 1410 men would need to be screened to prevent 1 death from prostate cancer. Evidence for the benefit of DRE screening is limited, and the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial, which included both PSA testing and DRE, showed no benefit. As far as mortality benefit is concerned, the evidence is inconsistent about whether screening reduces cancer-related death, and any absolute mortality risk reduction is probably small to none.

The harms of prostate cancer screening are substantial and include false alarms (suggesting that a patient may have cancer when he does not) related to high false-positive rates associated with DRE and especially the PSA test, overdiagnosis (that is, detecting cancer that will not cause future morbidity and mortality), high false-negative rates, anxiety, and discomfort. Positive screening results may lead to further testing, such as biopsies, which not only can be painful but can also lead to complications, such as infections, as well as overtreatment and the harms associated with it. In addition, currently available treatments are associated with harms, such as urinary, gastrointestinal, and sexual problems, as well as potential cardiovascular events and death. Data from Prostate Cancer Intervention Versus Observation Trial (PIVOT) showed that men who had radical prostatectomy had an 11% increased risk for urinary incontinence and a 37% increased risk for erectile dysfunction. Harms specific to DRE include discomfort and rectal bleeding.

Shared Decision-Making Approach

Clinicians should not screen for prostate cancer in men who do not wish to make the screening decision or do not express a clear preference about screening. However, some men would still prefer to be screened because they may put more value on the possible small benefit and less value on the harms. In these circumstances, shared decision-making is important in making choices about prostate cancer screening. Clinicians should elicit patient preferences for screening during the shared decision-making process and document them in the medical record. It is important to educate the patient about the following points and document the conversation in the medical record:

  1. Prostate cancer screening with the PSA test is controversial.
  2. Screening with the PSA test can detect prostate cancer, but for most men, the chances of harm from screening with the PSA test outweigh the chances of benefit.
  3. A small number of prostate cancer cases are serious and can cause death; however, the vast majority of prostate cancer is slow-growing and does not cause death.
  4. Most men who choose not to do PSA testing will not be diagnosed with prostate cancer and will die of something else.
  5. Patients who choose PSA testing are much more likely than those who decline PSA testing to be diagnosed with prostate cancer.
  6. The PSA test often does not distinguish between serious cancer and nonserious cancer. However, men with markedly elevated PSA levels (>10 µg/L) may have a reduced chance of dying from prostate cancer by having surgical treatment.
  7. The small potential benefit of prostate cancer screening corresponds to preventing, at most, 1 death caused by prostate cancer per 1000 men screened after 11 years of follow-up.
  8. There are many potential harms of screening. There may be problems in interpreting test results: The PSA test result may be high because of an enlarged prostate but not because of cancer, or it may be low even though cancer is present. Prostate biopsy, if needed, is also not free from risk. It involves multiple needles being inserted into the prostate under local anesthesia, and there is risk for infection or clinically significant bleeding and hospitalization (1.4%). If cancer is diagnosed, it will often be treated with surgery or radiation, which are associated with risks. There is a small risk for death with surgery, loss of sexual function (approximately 37% higher risk), and loss of control of urination (approximately 11% higher risk) compared with no surgery. These risks may vary depending on patient and surgeon characteristics and treatment method.
  9. The PSA test is not "just a blood test." It is a test that can open the door to more testing and treatment that a man may not actually want and that may actually harm him. A man's chances of being harmed are much greater than his chances of benefiting from the PSA test. Thus, each man should have the opportunity to decide for himself whether to have the PSA screening test.
  10. Studies are ongoing, so clinicians expect to learn more about the benefits and harms of screening, and recommendations may change over time. Men are also welcome to change their minds at any time by asking for screening that they have previously declined or discontinue screening that they have previously requested.

Although ACP did not evaluate the evidence on the reliability, validity, or benefits of using available decision aids, some examples are listed in Table 2 in the original guidance statement document.

It is important for clinicians to convey to patients who may want to be screened that evidence indicates, at best, small benefits as well as substantial harms. Men who do not have a clear preference for screening should not be screened, and this should be documented. Clinicians should help men judge the balance of benefits and harms and discuss whether the harms outweigh the potential reduction in prostate cancer mortality in their particular cases. To frame the discussion, clinicians can inform patients that the PSA test will increase their lifetime risk for prostate cancer from approximately 9% to 16%. Currently, the tradeoff between harms and benefits beyond 11 to 13 years of follow-up is unknown. Alternatively, although 3 in 100 men will die of prostate cancer (or 5 in 100 for African American men), this means that 97 in 100 men (or 95 in 100 African American men) will die of something else. Finally, although some men may avoid pain and discomfort commonly associated with advanced disease, this must be balanced against the possibility of incontinence, erectile dysfunction, and other side effects that result from certain forms of aggressive treatment.

The goal of screening for any disease is to identify an undiagnosed condition for which an effective treatment is available, and timely treatment can lead to improved clinical outcomes. Although the best treatment approach for prostate cancer is unknown, current management for prostate cancer includes active surveillance, radical prostatectomy, external beam radiation therapy, and brachytherapy. Research is needed to better identify cancer that is more likely to benefit from curative treatments, in which case, benefits are more likely to outweigh harms.

High-Risk Patients

Screening in high-risk men has not been demonstrated to be associated with different outcomes than screening in average-risk men. Risks for prostate cancer include African American race and a first-degree relative diagnosed with prostate cancer, especially before age 65 years. Patients with such risks should receive information about the uncertainties, risks, and potential benefits associated with prostate cancer screening beginning at age 45 years. Shared decision making is important in making choices about prostate cancer screening in high-risk men as well. Men at appreciably higher risk (multiple family members diagnosed with prostate cancer before age 65 years) should receive this information beginning at age 40 years.

Frequency of Screening

Currently, no clear evidence is available to guide decisions about the periodicity or frequency of the evaluation of risk for prostate cancer or discussion about the benefits and harms. Considering the harms of screening and modest mortality benefit, increasing the interval between screening tests may reduce harms. The PLCO trial, which screened annually, found no benefit, whereas the ERSPC trial, in which most participants were screened every 4 years (range, 2 to 7 years), did find benefit, suggesting that longer intervals may be indicated.

Guidance Statement 2: ACP recommends that clinicians should not screen for prostate cancer using the PSA test in average-risk men under the age of 50 years, men over the age of 69 years, or men with a life expectancy of less than 10 to 15 years.

Increasing age or the presence of a chronic comorbid illness that affects life expectancy substantially limits the potential benefits of prostate cancer screening compared with harms. Evidence presented in the guidelines shows substantial harms associated with prostate cancer screening and treatment relative to questionable benefits. Any benefit is even smaller in men older than 69 years because the cancer may not become clinically significant in a person's lifetime. For men younger than 50 years, the harms, such as erectile dysfunction and urinary incontinence, carry even more weight relative to any potential benefit. Hence, the harms of screening for prostate cancer outweigh the benefits in average-risk men younger than 50 years, men older than 69 years, or men who have a life expectancy less than 10 to 15 years. Therefore, clinicians should not screen men younger than 50 years, those aged 70 years or older, or men with substantial comorbid conditions and a life expectancy less than 10 to 15 years.

The figure in the original guidance statement document summarizes the recommendations and clinical considerations for prostate cancer screening.

AUA
(2013)

Age <40 years

Guideline Statement 1. The Panel recommends against PSA screening in men under age 40 years. (Recommendation; Evidence Strength Grade C)

In this age group there is a low prevalence of clinically detectable prostate cancer, no evidence demonstrating benefit of screening and likely the same harms of screening as in other age groups.

Age 40 to 54

Guideline Statement 2. The Panel does not recommend routine screening in men between ages 40 to 54 years at average risk. (Recommendation; Evidence Strength Grade C)

For men younger than age 55 years at higher risk (e.g., positive family history or African American race), decisions regarding prostate cancer screening should be individualized.

Age 55 to 69

Guideline Statement 3. For men ages 55 to 69 years the Panel recognizes that the decision to undergo PSA screening involves weighing the benefits of preventing prostate cancer mortality in one man for every 1,000 men screened over a decade against the known potential harms associated with screening and treatment. For this reason, the Panel strongly recommends shared decision-making for men age 55 to 69 years that are considering PSA screening, and proceeding based on men's values and preferences. (Standard; Evidence Strength Grade B)

The greatest benefit of screening appears to be in men ages 55 to 69 years.

Guideline Statement 4. To reduce the harms of screening, a routine screening interval of two years or more may be preferred over annual screening in those men who have participated in shared decision-making and decided on screening. As compared to annual screening, it is expected that screening intervals of two years preserve the majority of the benefits and reduce overdiagnosis and false positives. (Option; Evidence Strength Grade C)

Additionally, intervals for rescreening can be individualized by a baseline PSA level.

Age 70+

Guideline Statement 5. The Panel does not recommend routine PSA screening in men age 70+ years or any man with less than a 10 to 15 year life expectancy. (Recommendation; Evidence Strength Grade C)

Some men age 70+ years who are in excellent health may benefit from prostate cancer screening.

USPSTF
(2012)

Summary of Recommendations and Evidence

The USPSTF recommends against PSA–based screening for prostate cancer. This is a grade D recommendation.

Clinical Considerations

Implementation

Although the USPSTF discourages the use of screening tests for which the benefits do not outweigh the harms in the target population, it recognizes the common use of PSA screening in practice today and understands that some men will continue to request screening and some physicians will continue to offer it. The decision to initiate or continue PSA screening should reflect an explicit understanding of the possible benefits and harms and respect the patients' preferences. Physicians should not offer or order PSA screening unless they are prepared to engage in shared decision making that enables an informed choice by the patients. Similarly, patients requesting PSA screening should be provided with the opportunity to make informed choices to be screened that reflect their values about specific benefits and harms. Community- and employer-based screening should be discontinued. Table 3 in the original guideline document presents reasonable estimates of the likely outcomes of screening, given the current approach to screening and treatment of screen-detected prostate cancer in the United States.

The treatment of some cases of clinically localized prostate cancer can change the natural history of the disease and may reduce morbidity and mortality in a small percentage of men, although the prognosis for clinically localized cancer is generally good regardless of the method of detection, even in the absence of treatment. The primary goal of PSA-based screening is to find men for whom treatment would reduce morbidity and mortality. Studies demonstrate that the number of men who experience this benefit is, at most, very small, and PSA-based screening as currently implemented in the United States produces more harms than benefits in the screened population. It is not known whether an alternative approach to screening and management of screen-detected disease could achieve the same or greater benefits while reducing the harms. Focusing screening on men at increased risk for prostate cancer mortality may improve the balance of benefits and harms, but existing studies do not allow conclusions about a greater absolute or relative benefit from screening in these populations. Lengthening the interval between screening tests may reduce harms without affecting cancer mortality; the only screening trial that demonstrated a prostate cancer–specific mortality benefit generally used a 2- to 4-year screening interval. Other potential ways to reduce diagnostic- and treatment-related harms include increasing the PSA threshold used to trigger the decision for biopsy or need for treatment, or reducing the number of men having active treatment at the time of diagnosis through watchful waiting or active surveillance. Periodic DREs could also be an alternative strategy worthy of further study. In the only randomized trial demonstrating a mortality reduction from radical prostatectomy for clinically localized cancer, a high percentage of men had palpable cancer. All of these approaches require additional research to better elucidate their merits and pitfalls and more clearly define an approach to the diagnosis and management of prostate cancer that optimizes the benefits while minimizing the harms.

Patient Population Under Consideration

This recommendation applies to men in the general U.S. population. Older age is the strongest risk factor for the development of prostate cancer. However, neither screening nor treatment trials show benefit in men older than 70 years. Across age ranges, black men and men with a family history of prostate cancer have an increased risk of developing and dying of prostate cancer. Black men are approximately twice as likely to die of prostate cancer than other men in the United States, and the reason for this disparity is unknown. Black men represented a small minority of participants in the randomized clinical trials of screening (4% of enrolled men in the PLCO trial were non-Hispanic black; although the ERSPC and other trials did not report the specific racial demographic characteristics of participants, they likely were predominantly white). Thus, no firm conclusions can be made about the balance of benefits and harms of PSA-based screening in this population. However, it is problematic to selectively recommend PSA-based screening for black men in the absence of data that support a more favorable balance of risks and benefits. A higher incidence of cancer will result in more diagnoses and treatments, but the increase may not be accompanied by a larger absolute reduction in mortality. Preliminary results from PIVOT (Prostate Cancer Intervention Versus Observation Trial), in which 30% of enrollees were black, have become available since the publication of the USPSTF's commissioned evidence reviews. Investigators found no difference in outcomes due to treatment of prostate cancer in black men compared with white men.

Exposure to Agent Orange (a defoliant used in the Vietnam War) is considered to be a risk factor for prostate cancer, although few data exist on the outcomes or effect of PSA testing and treatment in these persons. Prostate cancer in Vietnam veterans who were exposed to Agent Orange is considered a service-connected condition by the Veterans Health Administration.

The USPSTF did not evaluate the use of the PSA test as part of a diagnostic strategy in men with symptoms potentially suggestive of prostate cancer. However, the presence of urinary symptoms was not an inclusion or exclusion criterion in screening or treatment trials, and approximately one quarter of men in screening trials had bothersome lower urinary tract symptoms (nocturia, urgency, frequency, and poor stream). The presence of benign prostatic hyperplasia is not an established risk factor for prostate cancer, and the risk for prostate cancer among men with elevated PSA levels is lower in men with urinary symptoms than in men without symptoms. This recommendation also does not include the use of the PSA test for surveillance after diagnosis or treatment of prostate cancer and does not consider PSA-based testing in men with known BRCA gene mutations who may be at increased risk for prostate cancer.

Screening Tests

PSA–based screening in men aged 50 to 74 years has been evaluated in 5 unique randomized, controlled trials of single or interval PSA testing with various PSA cutoffs and screening intervals, along with other screening methods, such as DRE or transrectal ultrasonography. Screening tests or programs that do not incorporate PSA testing, including DRE alone, have not been adequately evaluated in controlled studies.

No study found a difference in overall or all-cause mortality. This probably reflects the high rates of competing mortality in this age group, because these men are more likely to die of prostate cancer, as well as the limited power of prostate cancer screening trials to detect differences in all-cause mortality, should they exist.

Treatment

Primary management strategies for PSA-detected prostate cancer include watchful waiting (observation and physical examination with palliative treatment of symptoms), active surveillance (periodic monitoring with PSA tests, physical examinations, and repeated prostate biopsy) with conversion to potentially curative treatment at the sign of disease progression or worsening prognosis, and surgery or radiation therapy. There is no consensus about the optimal treatment of localized disease. From 1986 through 2005, PSA-based screening likely resulted in approximately 1 million additional U.S. men being treated with surgery, radiation therapy, or both compared with the time before the test was introduced.

Up to 0.5% of men will die within 30 days of having radical prostatectomy, and 3% to 7% will have serious surgical complications. Compared with men who choose watchful waiting, an additional 20% to 30% or more of men treated with radical prostatectomy will experience erectile dysfunction, urinary incontinence, or both after 1 to 10 years. Radiation therapy is also associated with increases in erectile, bowel, and bladder dysfunction.

ACP
(2013)

Not applicable

AUA
(2013)

Body of Evidence Strength

Grade A: Well-conducted and highly-generalizable randomized controlled trials (RCTs) or exceptionally strong observational studies with consistent findings

Grade B: RCTs with some weaknesses of procedure or generalizability or generally strong observational studies with consistent findings

Grade C: Observational studies that are inconsistent, have small sample sizes, or have other problems that potentially confound interpretation of data

Note: By definition, Grade A evidence is evidence about which the Panel has a high level of certainty, Grade B evidence is evidence about which the Panel has a moderate level of certainty, and Grade C evidence is evidence about which the Panel has a low level of certainty.

AUA Nomenclature Linking Statement Type to Evidence Strength

Standard: Directive statement that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be taken based on Grade A or B evidence

Recommendation: Directive statement that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be taken based on Grade C evidence

Option: Non-directive statement that leaves the decision regarding an action up to the individual clinician and patient because the balance between benefits and risks/burdens appears equal or appears uncertain based on Grade A, B, or C evidence

Clinical Principle: A statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature

Expert Opinion: A statement, achieved by consensus of the Panel, that is based on members' clinical training, experience, knowledge, and judgment for which there is no evidence

USPSTF
(2012)

What the USPSTF Grades Mean and Suggestions for Practice

Grade Grade Definitions Suggestions for Practice
A The USPSTF recommends the service. There is high certainty that the net benefit is substantial. Offer or provide this service.
B The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. Offer or provide this service.
C Note: The following statement is undergoing revision. Clinicians may provide this service to selected patients depending on individual circumstances. However, for most persons without signs or symptoms there is likely to be only a small benefit from this service. Offer/provide this service only if other considerations support offering or providing the service in an individual patient.
D The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. Discourage the use of this service.
I
Statement
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. Read "Clinical Considerations" section of USPSTF Recommendation Statement (see "Major Recommendations" field). If offered, patients should understand the uncertainty about the balance of benefits and harms.

USPSTF Levels of Certainty Regarding Net Benefit

Definition: The U.S. Preventive Services Task Force defines certainty as "likelihood that the USPSTF assessment of the net benefit of a preventive service is correct." The net benefit is defined as benefit minus harm of the preventive service as implemented in a general, primary care population. The USPSTF assigns a certainty level based on the nature of the overall evidence available to assess the net benefit of a preventive service.

Level of Certainty Description
High The available evidence usually includes consistent results from well-designed, well-conducted studies in representative primary care populations. These studies assess the effects of the preventive service on health outcomes. The conclusion is therefore unlikely to be strongly affected by the results of future studies.
Moderate The available evidence is sufficient to determine the effects of the preventive service on health outcomes, but confidence in the estimate is constrained by such factors as:
  • The number, size, or quality of individual studies
  • Inconsistency of findings across individual studies
  • Limited generalizability of findings to routine primary care practice
  • Lack of coherence in the chain of evidence
As more information becomes available, the magnitude or direction of the observed effect could change, and this change may be large enough to alter the conclusion.
Low The available evidence is insufficient to assess effects on health outcomes. Evidence is insufficient because of:
  • The limited number or size of studies
  • Important flaws in study design or methods
  • Inconsistency of findings across individual studies
  • Gaps in the chain of evidence
  • Findings that are not generalizable to routine primary care practice
  • A lack of information on important health outcomes
More information may allow an estimation of effects on health outcomes.
Click on the links below for details of guideline development methodology

ACP
(2013)

AUA
(2013)

USPSTF
(2012)

The methods used to develop the three guidelines differ. The AUA and USPSTF guidelines were developed from systematic reviews of the evidence, and the ACP guidance statement was derived from an appraisal of available guidelines on screening for prostate cancer. To develop the ACP guidance statement, authors searched the National Guideline Clearinghouse to identify prostate cancer screening guidelines developed by U.S.-based organizations, excluding any that restated the guidelines of other organizations (August 2012), and selected four, including the USPSTF guideline included in this synthesis and the previous (2009) version of the AUA guideline included in this synthesis. The other two guidelines were developed by the American College of Preventive Medicine (2008) and the American Cancer Society (2010). The AGREE II (Appraisal of Guidelines, Research and Evaluation in Europe) instrument was used to independently evaluate the selected guidelines by four coauthors. Expert consensus was used to formulate the recommendations based on the results of the critical appraisal and on the evidence. The guidance statement was validated using an internal peer review process and an independent peer-review process before publication.

With regard to the methods used to develop the AUA and USPSTF guidelines, both guideline developers performed searches of electronic databases and hand-searches of published literature (primary and secondary sources) to collect/select the evidence, and provide details regarding the process, including date ranges, search terms and inclusion/exclusion criteria. Systematic evidence reviews were prepared by the Agency for Healthcare Research and Quality (AHRQ) and the Oregon Evidence-based Practice Center (EPC) for use in the development of the USPSTF guideline. Similarly, AUA commissioned an independent group to conduct a systematic review of the published literature. To evaluate the quality and strength of the evidence, both AUA and USPSTF assessed it according to a rating scheme. To analyze the selected evidence, the guideline developers performed a systematic review with evidence tables and also reviewed published meta-analyses. The development of the AUA guideline is different from that of USPSTF in that the AUA commissioned an independent group to conduct a meta-analysis of the published literature. Methods used to formulate the recommendations were similar, with both of the developers using expert consensus (AUA specifies the Delphi technique was used); USPSTF also employed balance sheets. AUA and USPSTF rate the strength of the recommendations according to a scheme. To validate their guidelines, both developers sought some form of peer review (USPSTF specifies both internal and external peer review; USPSTF also compared its guideline with those of other groups, including the previous version of the AUA guideline). The USPSTF peer review process entailed posting of the draft recommendations on the Task Force Web site for public comment. The comments were discussed by the USPSTF before the final recommendations were confirmed.

Benefits

ACP
(2013)

The small potential benefit of prostate cancer screening corresponds to preventing, at most, 1 death caused by prostate cancer per 1000 men screened after 11 years of follow-up.

AUA
(2013)
  • Appropriate use of prostate cancer screening
  • An approach to PSA based prostate cancer screening has to take into account the controversies surrounding available data and the fact that over a decade the benefits are modest in terms of prostate cancer deaths averted; 1 death per 1,000 men screened in the European Randomized Study of Screening for Prostate Cancer. However the relative benefit (20% reduction in disease-specific deaths) could be very meaningful at the population level. The potential benefits of screening could extend beyond survival as a primary outcome, and will depend on the relevant time horizon for an individual. Further, disconnecting screening from automatic treatment will significantly impact the risk benefit ratio.

Refer to the "Benefits of PSA Screening" section in the original guideline document for additional discussion.

USPSTF
(2012)

Benefits of Detection and Early Treatment

The primary goal of prostate cancer screening is to reduce deaths due to prostate cancer and, thus, increase length of life. An additional important outcome would be a reduction in the development of symptomatic metastatic disease. Reduction in prostate cancer mortality was the primary outcome used in available randomized, controlled trials of prostate cancer screening. Although one screening trial reported on the presence of metastatic disease at the time of prostate cancer diagnosis, no study reported on the effect of screening on the development of subsequent metastatic disease, making it difficult to assess the effect of lead-time bias on the reported rates.

Men with screen-detected cancer can potentially fall into one of three categories: those whose cancer will result in death despite early diagnosis and treatment, those who will have good outcomes in the absence of screening, and those for whom early diagnosis and treatment improves survival. Only randomized trials of screening allow an accurate estimate of the number of men who fall into the latter category. There is convincing evidence that the number of men who avoid dying of prostate cancer because of screening after 10 to 14 years is, at best, very small. Two major trials of PSA screening were considered by the USPSTF: the U.S. PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial and the ERSPC (European Randomised Study of Screening for Prostate Cancer). The U.S. trial did not demonstrate any prostate cancer mortality reduction. The European trial found a reduction in prostate cancer deaths of approximately 1 death per 1000 men screened in a subgroup of men aged 55 to 69 years. This result was heavily influenced by the results of two countries; five of the seven countries reporting results did not find a statistically significant reduction. All-cause mortality in the European trial was nearly identical in the screened and nonscreened groups.

There is adequate evidence that the benefit of PSA screening and early treatment ranges from 0 to 1 prostate cancer deaths avoided per 1000 men screened.

Harms

ACP
(2013)
  • The harms of prostate cancer screening are substantial and include false alarms (suggesting that a patient may have cancer when he does not) related to high false-positive rates associated with DRE and especially the PSA test, overdiagnosis (that is, detecting cancer that will not cause future morbidity and mortality), high false-negative rates, anxiety, and discomfort.
  • Positive screening results may lead to further testing, such as biopsies, which not only can be painful but can also lead to complications, such as infections, as well as overtreatment and the harms associated with it. In addition, currently available treatments are associated with harms, such as urinary, gastrointestinal, and sexual problems, as well as potential cardiovascular events and death. Data from Prostate Cancer Intervention Versus Observation Trial (PIVOT) showed that men who had radical prostatectomy had an 11% increased risk for urinary incontinence and a 37% increased risk for erectile dysfunction. Harms specific to DRE include discomfort and rectal bleeding.
AUA
(2013)

Harms from Screening

  • Prostate cancer screening itself is associated with a number of potential harms, both psychological and physical.
  • The transrectal or transperineal prostate biopsy has risks of hematuria, hematochezia, hematospermia, dysuria and retention, pain, and infection. Hematuria and hematospermia are the most frequently observed side effects with wide variation in observed rates. Hematospermia after biopsy occurs in 10% to 70% of patients while hematuria is seen 14% to 50% of the time. While the risk of hospitalization due to bleeding complications remains low, infectious complications are increasing steadily over time, possibly due to fluoroquinolone resistance. The 30-day risk of hospitalization after biopsy for any cause has been estimated to be approximately 4%, of which three in four are for infections. The use of routine fecal culture and sensitivity tailored antibiotic prophylaxis may be one approach to reduce infection rates.
  • The AUA has published a white paper to provide some guidance regarding periprocedural prophylaxis. Since prostate biopsies are also an important part of some active surveillance programs, understanding these risks and communicating them to patients is not only integral to informed consent for prostate cancer screening but also for consideration of treatment options.
  • Once diagnosed with prostate cancer, a man is faced with the risk of overtreatment of indolent disease due to the assumption that diagnosis with a malignancy must necessarily result in treatment of this malignancy. Estimates of overdiagnosis vary widely from less than 5% to more than 75% depending upon the population used with lead times of 5 to 15 years.
  • Although prostate cancer specific mortality and the need for related palliative care is decreased by screening, quality of life may be impaired as a result due to lasting impairment in urinary, bowel, and sexual function.
  • There is considerable distress involved in the decision making process, the biopsy, and deciding among treatment options. Along with the stress due to PSA screening and unnecessary biopsies, the diagnosis of prostate cancer alone may incite severe psychological stress with one study showing an increased rate of suicide and cardiovascular events in newly diagnosed men.
  • Even when men select active surveillance rather than curative therapy, anxiety may continue and trigger intervention in men who would never have needed treatment in their lifetime; although it would appear that anxiety remains low for most men on surveillance in the short term.

Refer to the "Harms" section in the original guideline document for additional discussion.

USPSTF
(2012)

Harms of Detection and Early Treatment

Harms Related to Screening and Diagnostic Procedures

Convincing evidence demonstrates that the PSA test often produces false-positive results (approximately 80% of positive PSA test results are false-positive when cutoffs between 2.5 and 4.0 μg/L are used). There is adequate evidence that false-positive PSA test results are associated with negative psychological effects, including persistent worry about prostate cancer. Men who have a false-positive test result are more likely to have additional testing, including 1 or more biopsies in the following year, than those who have a negative test result. Over 10 years, approximately 15% to 20% of men will have a PSA test result that triggers a biopsy, depending on the PSA threshold and testing interval used. New evidence from a randomized trial of treatment of screen-detected cancer indicates that roughly one third of men who have prostate biopsy experience pain, fever, bleeding, infection, transient urinary difficulties, or other issues requiring clinician follow-up that the men consider a "moderate or major problem"; approximately 1% require hospitalization. The USPSTF considered the magnitude of these harms associated with screening and diagnostic procedures to be at least small.

Harms Related to Treatment of Screen-Detected Cancer

Adequate evidence shows that nearly 90% of men with PSA-detected prostate cancer in the United States have early treatment with surgery, radiation, or androgen deprivation therapy. Adequate evidence shows that up to 5 in 1000 men will die within 1 month of prostate cancer surgery and between 10 and 70 men will have serious complications but survive. Radiotherapy and surgery result in long-term adverse effects, including urinary incontinence and erectile dysfunction in at least 200 to 300 of 1000 men treated with these therapies. Radiotherapy is also associated with bowel dysfunction.

Some clinicians have used androgen deprivation therapy as primary therapy for early-stage prostate cancer, particularly in older men, although this is not a U.S. Food and Drug Administration (FDA)–approved indication and it has not been shown to improve survival in localized prostate cancer. Adequate evidence shows that androgen deprivation therapy for localized prostate cancer is associated with erectile dysfunction (in approximately 400 of 1000 men treated), as well as gynecomastia and hot flashes.

There is convincing evidence that PSA-based screening leads to substantial overdiagnosis of prostate tumors. The amount of overdiagnosis of prostate cancer is of important concern because a man with cancer that would remain asymptomatic for the remainder of his life cannot benefit from screening or treatment. There is a high propensity for physicians and patients to elect to treat most cases of screen-detected cancer, given our current inability to distinguish tumors that will remain indolent from those destined to be lethal. Thus, many men are being subjected to the harms of treatment of prostate cancer that will never become symptomatic. Even for men whose screen-detected cancer would otherwise have been later identified without screening, most experience the same outcome and are, therefore, subjected to the harms of treatment for a much longer period of time. There is convincing evidence that PSA-based screening for prostate cancer results in considerable overtreatment and its associated harms.

The USPSTF considered the magnitude of these treatment-associated harms to be at least moderate.

ACP, American College of Physicians

AUA, American Urological Association Education and Research, Inc.

DRE, digital rectal examination

ERSPC, European Randomised Study of Screening for Prostate Cancer

PLCO, Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

PSA, prostate specific antigen

USPSTF, U.S. Preventive Services Task Force

This synthesis was prepared by ECRI Institute on December 28, 1998. This synthesis was updated in 2005 to add recommendations from UMHS and to remove recommendations from AUA and SMOH. The information was verified by UMHS on August 23, 2005. This synthesis was updated on December 6, 2007 to remove recommendations from USPSTF. This synthesis was revised on June 13, 2008 to add ACPM recommendations. The information was verified by ACPM on July 17, 2008. This synthesis was revised in October 2008 to add USPSTF recommendations in March 2009 to remove recommendations from ACS and in March 2010 to remove UMHS recommendations and add AUA recommendations. The information was verified by AUA on April 12, 2010. This synthesis was revised in December 2011 to add recommendations from ACS. The updated information was verified by ACS on January 19, 2012. This synthesis was revised in March 2013 to update recommendations from USPSTF and remove recommendations from ACPM. The information was verified by USPSTF on April 1, 2013. This synthesis was revised in May 2013 to remove AUA recommendations. This synthesis was revised in February 2014 to add updated recommendations from AUA. The information was verified by AUA on February 17, 2014. This synthesis was revised most recently in October 2015 to add recommendations from ACP and remove recommendations from ACS. The information was verified by ACP on October 22, 2015.

About NGC Guideline Syntheses

Syntheses are systematic comparisons of selected guidelines that address similar topics. For definitions of synthesis attributes, see the Guideline Synthesis Template.


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