Table 32: Sensitivity and Specificity of PSA Test, By Age, PSA Value, and Race (Morgan 1996)

National Prostate Cancer Screening Clinical Practice Guideline

Quality Assessment

No quantitative GRADE system exists for diagnostic studies, and no risk of bias tools for observational studies have been evaluated. Based on qualitative assessment of the body of literature, the quality of evidence to determine performance characteristics (sensitivity, specificity, etc.) of PSA and DRE is very low. This is also true for studies which examined the use of age-specific PSA thresholds. Due to the high degree of missing biopsies among those with “normal” PSA results, accurate measures of

diagnostic accuracy cannot be calculated. As such, there continues to be a high-risk of bias in these studies, resulting in the quality of evidence likely being very low.

National Prostate Cancer Screening Clinical Practice Guideline

External Guidelines

NCCN, ACS, ACP and AUA recommend a shared decision-making approach to discuss the benefits and risk of prostate cancer screening. NCCN outlines an algorithm for baseline PSA testing at 40 years, ACS continues to recommend discussing screening at 45 years for high-risk and 50 years for average risk, AUA recommends a shared

decision-making approach in men 55-69 years, and ACP recommends a shared decision-making approach in men ages 50-69 years. USPSTF recommends against prostate cancer screening, citing harms outweighing the potential benefits of screening. Nonetheless, the USPSTF also outlines points to use in an informed decision-making discussion.

NCCN 2012

The NCCN prostate cancer early detection CPG presents a series of algorithms for PSA-based screening in the context of a shared decision-making discussion: “Start risk and benefit discussion about offering baseline digital rectal examination (DRE) and PSA at age 40”.

ACS

http://www.cancer.org/healthy/findcancerearly/cancerscreeningguidelines/american- cancer-society-guidelines-for-the-early-detection-of-cancer

“The American Cancer Society recommends that men make an informed decision with their doctor about whether to be tested for prostate cancer. Research has not yet

proven that the potential benefits of testing outweigh the harms of testing and treatment. The American Cancer Society believes that men should not be tested without learning about what we know and don’t know about the risks and possible benefits of testing and treatment.

Starting at age 50, men should talk to a doctor about the pros and cons of testing so they can decide if testing is the right choice for them. If they are African American or have a father or brother who had prostate cancer before age 65, men should have this talk with a doctor starting at age 45. If men decide to be tested, they should have the PSA blood test with or without a rectal exam. How often they are tested will depend on their PSA level.”

AUA 2013

The current AUA guidelines for early detection of prostate cancer address average-risk men in 4 age groups: <40, 40-54, 55-69 and ≥70 years. AUA recommends against screening in men under 40, 70 years or greater, or men with <10 to 15 year life

National Prostate Cancer Screening Clinical Practice Guideline

54. For men ages 55-69 years, AUA recommends a shared decision-making approach in men who are considering PSA screening.

The guideline statements are as follows (reported verbatim):

“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.

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.

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 1 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 a man’s values and preferences. (Standard; Evidence Strength Grade B)

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

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.

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

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

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American College of Physicians 2013 (ACP)

“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 prostate specific antigen 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 prostate-specific antigen test in patients who do not express a clear preference for screening.

Guidance Statement 2: ACP recommends that clinicians should not screen for

prostate cancer using the prostate-specific antigen 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”.

USPSTF

“The U.S. Preventive Services Task Force (USPSTF) recommends against prostate- specific antigen (PSA)-based screening for prostate cancer (D recommendation).” In their rationale, USPSTF goes on to state:

“Although the precise, long-term effect of PSA screening on prostate cancer–specific mortality remains uncertain, existing studies adequately demonstrate that the reduction in prostate cancer mortality after 10 to 14 years is, at most, very small, even for men in what seems to be the optimal age range of 55 to 69 years. There is no apparent

reduction in all-cause mortality. In contrast, the harms associated with the diagnosis and treatment of screen-detected cancer are common, occur early, often persist, and

include a small but real risk for premature death. Many more men in a screened population will experience the harms of screening and treatment of screen-detected disease than will experience the benefit. The inevitability of overdiagnosis and overtreatment of prostate cancer as a result of screening means that many men will experience the adverse effects of diagnosis and treatment of a disease that would have remained asymptomatic throughout their lives. Assessing the balance of benefits and harms requires weighing a moderate to high probability of early and persistent harm from treatment against the very low probability of preventing a death from prostate cancer in the long term.

The USPSTF concludes that there is moderate certainty that the benefits of PSA-based screening for prostate cancer do not outweigh the harms.”

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(19) Zeegers MP, Jellema A, Ostrer H. Empiric risk of prostate carcinoma for relatives of patients with prostate carcinoma: a meta-analysis. Cancer 2003;97:1894-1903. (20) Ilic D ODGSWTJ. Screening for prostate cancer. 2010. Cochrane Database of

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(37) Thompson IM, Pauler DK, Goodman PJ et al. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med

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(39) Maattanen L, Hakama M, Tammela TL et al. Specificity of serum prostate-specific antigen determination in the Finnish prostate cancer screening trial. Br J Cancer 2007;96:56-60.

(40) Hakama M, Stenman UH, Aromaa A, Leinonen J, Hakulinen T, Knekt P. Validity of the prostate specific antigen test for prostate cancer screening: followup study with a bank of 21,000 sera in Finland. J Urol 2001;166:2189-2191.

(41) Morgan TO, Jacobsen SJ, McCarthy WF, Jacobson DJ, McLeod DG, Moul JW. Age- specific reference ranges for prostate-specific antigen in black men. N Engl J Med 1996;335:304-310.

(42) Jacobsen SJ, Guess HA, Oesterling JE. Re: Selection of optimal prostate specific antigen cutoffs for early detection of prostate cancer: receiver operating characteristic curves. J

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(43) Oesterling JE, Jacobsen SJ, Chute CG et al. Serum prostate-specific antigen in a community-based population of healthy men. Establishment of age-specific reference ranges. JAMA 1993;270:860-864.

(44) Oesterling JE, Jacobsen SJ, Cooner WH. The use of age-specific reference ranges for serum prostate specific antigen in men 60 years old or older. J Urol 1995;153:1160-1163. (45) Partin AW, Criley SR, Subong EN, Zincke H, Walsh PC, Oesterling JE. Standard versus

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Appendix A

Table A-1. Criteria for Assigning Grades of Evidence for Each Outcome14

Type of evidence

Randomized trial High

Observational study Low

Any other evidence Very low

Decrease grade

Serious limitation to study quality -1 Very serious limitation to study quality -2

Important inconsistency -1

Some uncertainty about directness -1 Major uncertainty about directness -2

Imprecise or sparse data -1

High probability of reporting bias -1

Increase grade

Strong evidence of association: Significant RR of >2 (<0.5) based on consistent evidence from two or more observational studies, with no plausible confounders

Very strong evidence of association: Significant RR of >5 (<0.2) based on direct evidence with no major threats to validity

All plausible confounders would have reduced the effect

Table A-2. GRADE Levels of Evidence across outcomes Grade Definition

High Further research is very unlikely to change our confidence in the estimate of effect.

Moderate Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low Any estimate of effect is very uncertain.

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Table A-3: Determinants of strength of recommendation15

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Appendix B

In document Prostate Cancer Screening Clinical Practice Guideline. Approved by the National Guideline Directors November, 2013 (Page 96-107)