Recommendation Statement
U.S. Preventive Services Task Force (USPSTF)
Date: August 2008
Summary of Recommendations
- The USPSTF concludes that the current evidence is
insufficient to assess the balance of benefits and harms of
prostate cancer screening in men younger than age 75
years.
Grade: I statement.
- The USPSTF recommends against screening for prostate
cancer in men age 75 years or older.
Grade: D recommendation.
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This recommendation statement was first published in Annals of Internal Medicine. Select for copyright and source information.
Contents
Rationale
Clinical Considerations
Other Considerations
Discussion
Recommendations of Other Groups
References
Members of the USPSTF
Rationale
Importance
Prostate cancer is the most common nonskin cancer
and the second leading cause of cancer death in men in the
United States.
Detection
The USPSTF found convincing evidence that prostate-specific antigen (PSA) screening can detect some cases
of prostate cancer.
Benefits of Detection and Early Treatment
In men younger than age 75 years, the USPSTF found
inadequate evidence to determine whether treatment for
prostate cancer detected by screening improves health outcomes
compared with treatment after clinical detection.
In men age 75 years or older, the USPSTF found
adequate evidence that the incremental benefits of treatment
for prostate cancer detected by screening are small to
none.
Harms of Detection and Early Treatment
The USPSTF found convincing evidence that treatment
for prostate cancer detected by screening causes moderate-to-substantial harms, such as erectile dysfunction,
urinary incontinence, bowel dysfunction, and death. These harms are especially important because some men with
prostate cancer who are treated would never have developed
symptoms related to cancer during their lifetime.
There is also adequate evidence that the screening process
produces at least small harms, including pain and discomfort
associated with prostate biopsy and psychological effects
of false-positive test results.
USPSTF Assessment
The USPSTF concludes that for men younger than
age 75 years, the benefits of screening for prostate cancer
are uncertain and the balance of benefits and harms cannot
be determined.
For men 75 years or older, there is moderate certainty
that the harms of screening for prostate cancer outweigh
the benefits.
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Clinical Considerations
Patient Population Under Consideration
This recommendation applies to men in the general
U.S. population.
Assessment of Risk
Older men, African-American men, and men with a
family history of prostate cancer are at increased risk for
diagnosis of and death from prostate cancer.1 Unfortunately,
the previously described gaps in the evidence regarding
potential benefits of screening also apply to these
men.
Screening Tests
The PSA test is more sensitive than the digital rectal
examination for detecting prostate cancer. The conventional
PSA screening cut-point of 4.0 µg/L detects many
cases of prostate cancer; however, some early cases will be
missed by this cut-point.2,3 Using a lower cut-point to
define an abnormal PSA level detects more cases of cancer.
The proportion of cancer cases detected by lower cutpoints
that would ever become clinically apparent is unknown;
lower cut-points would label many more men as
potentially having cancer. For example, lowering the PSA
cut-point to 2.5 µg/L would more than double the number
of U.S. men between 40 and 69 years of age with
abnormal results.4
Variations of PSA screening, including the use of ageadjusted
PSA cut-points, free PSA, PSA density, PSA velocity,
PSA slope, and PSA doubling time, have been proposed
to improve detection of "clinically important"
prostate cancer cases. However, no evidence suggests that
any of these testing strategies improves health outcomes.2,5
Suggestions for Practice
Given the uncertainties and controversy surrounding
prostate cancer screening in men younger than age 75
years, a clinician should not order the PSA test without
first discussing with the patient the potential but uncertain
benefits and the known harms of prostate cancer screening and treatment. Men should be informed of the gaps in the
evidence and should be assisted in considering their personal
preferences before deciding whether to be tested.
Treatment
Because of the uncertainty about the benefits of treating
prostate cancer detected by screening men younger
than age 75 years, there is no consensus regarding optimal
treatment. Current management strategies for localized
prostate cancer include watchful waiting (observation with
palliative treatment for symptoms only), active surveillance
(periodic biochemical monitoring with conversion to curative
treatment for signs of disease progression), radical
prostatectomy, external-beam radiation therapy, and
brachytherapy (or radioactive seed implantation therapy).6
If treatment for prostate cancer detected by screening
improves health outcomes, the population most likely to
benefit from screening will be men age 50 to 74 years.
Even if prostate cancer screening is determined to be effective,
the length of time required to experience a mortality
benefit is greater than 10 years. Because a 75-year-old man
has an average life expectancy of about 10 years, very few
men age 75 years or older would experience a mortality
benefit. Similarly, men younger than age 75 years who
have chronic medical problems and a life expectancy of
fewer than 10 years are also unlikely to benefit from screening
and treatment.2
Screening Intervals
The yield of screening in terms of cancer cases detected
declines rapidly with repeated annual testing. If
screening were to reduce deaths, PSA screening as infrequently
as every 4 years could yield as much of a benefit as
annual screening.7
Useful Resources
Shared decision-making resources specific to prostate
cancer screening for clinicians and patients are available
from the Centers of Disease Control and Prevention (www.cdc.gov/cancer/prostate/publications/).
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Other Considerations
Research Needs/Gaps
Good-quality randomized, controlled trials (RCTs) are
needed to establish the effect, if any, of population-based
PSA screening on prostate cancer mortality in men
younger than age 75 years. The results of 2 ongoing trials,
the U.S. Prostate, Lung, Colorectal, and Ovarian Cancer
Screening Trial and the European Study of Screening for
Prostate Cancer, should help to clarify the potential benefits
of screening.
Future studies should identify testable characteristics
of screening-detected prostate cancer that reliably predict
poor health outcomes and that therefore may be indications
for treatment. Research is needed to compare the
long-term benefits of immediate treatment with delayed treatment in men with screening-detected prostate cancer.
Two ongoing RCTs, the U.S. Prostate Intervention Versus
Observation Trial and the U.K. Prostate Testing for Cancer
and Treatment Study, are studying these issues.
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Discussion
Burden
of Disease
An estimated 218 890 U.S. men received a prostate
cancer diagnosis in 2007, and 1 of 6 men in the U.S. will
receive the diagnosis in his lifetime.8 An estimated
27,350 men died of prostate cancer in the United States in
2006.1 The median age of death from prostate cancer
from 2000 through 2004 was 80 years, and 71% of deaths
occurred in men older than 75 years. African-American
men have a substantially higher prostate cancer incidence
rate than white men (217.5 vs. 134.5 cases per 100 000
men) and more than twice the prostate cancer mortality
rate of white men (56.1 vs. 23.4 deaths per 100 000 men).9
Prostate cancer is a clinically heterogeneous disease. A
substantial proportion of prostate cancer cases detected
with current screening methods will never cause symptoms
during the patients' lifetime. Modeling studies based on
U.S. incidence data suggest overdiagnosis rates ranging
from 29% to 44% of all prostate cancer cases detected by
PSA screening.10 Because patients with "pseudo-disease"
receive no benefit from, and may be harmed by, prostate
cancer screening and treatment, prostate cancer detection
in this population constitutes an important burden.
Scope of USPSTF
Review
The previous review, performed for the USPSTF in
2002, found insufficient evidence that screening for prostate
cancer improved health outcomes, including mortality.
It also found little evidence on the harms of the screening
process or the natural history of prostate cancer cases detected
with screening.2 The USPSTF determined that a
focused evidence update5 should systematically review
direct evidence that PSA screening reduces morbidity and
mortality, evidence on the magnitude and nature of harms
associated with false-positive screening results, and evidence
on health outcomes of patients with screeningdetected
prostate cancer who did not receive active treatment.
Accuracy
of Screening Tests
The 2002 review noted inherent problems with the
use of needle biopsy results as a reference standard to assess
the accuracy of prostate cancer screening tests. Biopsy detection
rates vary according to the number of biopsies performed
during a single procedure: The more biopsies performed,
the more cancer cases detected. More cancer cases
detected with a "saturation" (>20) biopsy procedure tend
to increase the apparent specificity of an elevated PSA level;
however, many additional cancer cases detected this way
are likely to be clinically unimportant. Thus, the accuracy of the PSA test for detecting clinically important prostate
cancer cases cannot be determined with precision.
Longitudinal follow-up has also been used as a reference
standard. A retrospective study found the sensitivity
of a PSA level of 4.0 µg/L or higher to be about 91% for
detecting aggressive cases of prostate cancer that developed
within 2 years of screening; the sensitivity was about 56%
for detecting nonaggressive cancer cases within the same
period. Among men who did not receive a prostate cancer
diagnosis within 10 years, 9% had an initial PSA level of
4.0 µg/L or greater (which translates to a specificity of
91% for any prostate cancer).11
Effectiveness
of Early Detection and Treatment
A meta-analysis of 2 poor-quality RCTs of population-based screening for prostate cancer using PSA and
digital rectal examination found no reduction in prostate
cancer mortality in men invited versus men not invited for
screening (relative risk, 1.01 [95% CI, 0.80 to 1.29]).12
A recent RCT reported that men who received PSA screening
had a decreased risk for receiving a diagnosis of metastatic
prostate cancer.13 The USPSTF assessed the study
as providing inconclusive evidence of benefit from screening
because of a high likelihood of unequal outcome ascertainment
and small absolute numbers of an imperfect intermediate
health outcome (metastatic prostate cancer is an
imperfect surrogate of prostate cancer mortality because of
both high initial response rates to androgen deprivation
therapy and competing causes of death). No RCTs have
reported health outcomes from the variations of PSA
screening that consist of multiple measurements over time
(for example, measurements of PSA velocity, PSA slope, or
PSA doubling time).
Randomized, controlled trials comparing prostate cancer
treatments with watchful waiting have enrolled few patients
with screening-detected prostate cancer. An RCT of
695 men with localized prostate cancer reported a small
absolute reduction in all-cause mortality in patients assigned
to radical prostatectomy; however, only 5.2% of
participants had screening-detected prostate cancer, more
than 40% presented with symptoms, and 77.8% of the
treatment group had stage T2 (palpable) cancer.14 This
stage of cancer is more advanced than cancer typically detected
by screening. Yet, after a median of 8.2 years, only
14.4% of men in the control group and 8.6% of men in
the treatment group had died of prostate cancer.
Screening-detected cancer is biologically less aggressive,
is being detected much earlier in its natural history, or
both, so it is unlikely that these results could be obtained
in a study of screening-detected cancer in this same time
frame. Even if the same disease-specific results could be
obtained with a longer time frame, competing causes of
death would make any reduction in all-cause mortality less
than that found in the study. It is noteworthy that in the
372 men who were at least 65 years of age at the time of
diagnosis, the 10-year incidence of death from prostate cancer was similar between the watchful waiting and radical
prostatectomy groups, suggesting no benefit from surgery
in this age group.14
Estimate of Magnitude of Net Benefit
In men younger than age 75 years, the USPSTF could
not determine the net benefit of screening for prostate cancer
because of low certainty about the magnitude of benefits
of screening and treatment.
In men age 75 years or older, the USPSTF found no
direct evidence of benefits of prostate cancer screening.
However, the USPSTF was able to establish an upper
bound for the potential magnitude of the benefit of treating
screening-detected prostate cancer in this age group, by
extrapolating from evidence of treatment for clinically detected
prostate cancer in this age group.14 For a population
of men with an average life expectancy of 10 years or
fewer, the USPSTF determined that the benefits of prostate
cancer screening and treatment would range from
small to none.
Weighing this magnitude of benefit against the moderate-to-substantial psychological and physical harms associated
with prostate cancer screening and treatment, the
USPSTF concluded that there is at least moderate certainty
that the harms of screening for prostate cancer in men age
75 years or older outweigh the benefits.
How Does Evidence Fit with Biological Understanding?
Prostate-specific antigen screening presupposes that
most asymptomatic prostate cancer cases will ultimately
become symptomatic cases that lead to poor health outcomes.
However, the natural history of PSA-detected, nonpalpable,
localized prostate cancer is poorly described. No
prospective studies have followed a population-based cohort
of patients with screening-detected cancer who have
had no intervention in order to determine health outcomes
resulting from natural progression of the disease. Evidence
from small, selected cohorts of men with arbitrarily defined
"favorable risk" (that is, with prostate cancer likely to be
clinically indolent) suggest a good prognosis for some men
with screening-detected cancer; however, the longest of
these studies has reported health outcomes from 2 to 10
years after diagnosis only.5
Update of Previous USPSTF Recommendation
This recommendation replaces the 2002 recommendation.
The major change in the current recommendation is
that the USPSTF now recommends against screening men
age 75 years or older for prostate cancer.
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Recommendations
of Other Groups
Most major U.S. medical organizations recommend
that clinicians discuss the potential benefits and known
harms of PSA screening with their patients, consider their
patients' preferences, and individualize screening decisions.
They generally agree that the most appropriate candidates
for screening include men age 50 years or older who have a life expectancy of at least 10 years. These organizations
include the American Academy of Family Physicians,
American College of Physicians,16 American College of
Preventive Medicine,17 and American Medical Association.
The American Cancer Society18 and American
Urological Association19 recommend offering PSA measurement
and digital rectal examination to men annually
beginning at age 50 years.
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References
1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics,
2007. CA Cancer J Clin 2007;57:43-66. [PMID: 17237035]
2. Harris R, Lohr KN. Screening for prostate cancer: an update of the evidence
for the U.S. Preventive Services Task Force. Ann Intern Med 2002;137:917-29.
[PMID: 12458993]
3. Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes
HL, et al. Prevalence of prostate cancer among men with a prostate-specific
antigen level < or = 4.0 ng per milliliter. N Engl J Med 2004;350:2239-46.
[PMID: 15163773]
4. Welch HG, Schwartz LM, Woloshin S. Prostate-specific antigen levels in the
United States: implications of various definitions for abnormal. J Natl Cancer
Inst 2005;97:1132-7. [PMID: 16077071]
5. Lin K, Lipsitz R, Miller T, Janakiraman S. Benefits and harms of prostate-specific
antigen screening for prostate cancer: an evidence update for the U.S.
Preventive Services Task Force. Ann Intern Med 2008;149:192-9.
6. Wilt TJ, Shamliyan T, Taylor B, MacDonald R, Tacklind J, Rutks I, et al.
Comparative Effectiveness of Therapies for Clinically Localized Prostate Cancer.
(Prepared by Minnesota Evidence-based Practice Center under contract no. 290-02-00009.) Rockville, MD: Agency for Healthcare Research and Quality; 2008.
Comparative Effectiveness Review no. 13. AHRQ publication no. 08-EHC010-1. Accessed at http://effectivehealthcare.ahrq.gov/healthInfo.cfm on 3
June 2008.
7. Roobol MJ, Grenabo A, Schröder FH, Hugosson J. Interval cancers in prostate
cancer screening: comparing 2- and 4-year screening intervals in the European
Randomized Study of Screening for Prostate Cancer, Gothenburg and Rotterdam.
J Natl Cancer Inst 2007;99:1296-303. [PMID: 17728218]
8. National Cancer Institute, Surveillance Epidemiology and End Results
(SEER). Cancer Stat Fact Sheets: Cancer of the Prostate. Rockville, MD: National
Institutes of Health. Accessed at http://seer.cancer.gov/statfacts/html/prost.html on 3 June 2008.
9. U.S. Cancer Statistics Working Group. United States Cancer Statistics:
1999–2004 Incidence and Web-based Report. Atlanta: Centers for Disease Control
and Prevention; 2007. Accessed at www.cdc.gov/uscs on 3 June 2008.
10. Etzioni R, Penson DF, Legler JM, di Tommaso D, Boer R, Gann PH, et al.
Overdiagnosis due to prostate-specific antigen screening: lessons from U.S. prostate
cancer incidence trends. J Natl Cancer Inst 2002;94:981-90. [PMID:
12096083]
11. Gann PH, Hennekens CH, Stampfer MJ. A prospective evaluation of
plasma prostate-specific antigen for detection of prostatic cancer. JAMA 1995;
273:289-94. [PMID: 7529341]
12. Ilic D, O'Connor D, Green S, Wilt T. Screening for prostate cancer.
Cochrane Database Syst Rev 2006;3:CD004720. [PMID: 16856057]
13. Aus G, Bergdahl S, Lodding P, Lilja H, Hugosson J. Prostate cancer screening
decreases the absolute risk of being diagnosed with advanced prostate cancer—results from a prospective, population-based randomized controlled trial.
Eur Urol 2007;51:659-64. [PMID: 16934392]
14. Bill-Axelson A, Holmberg L, Ruutu M, Häggman M, Andersson SO,
Bratell S, et al. Scandinavian Prostate Cancer Group Study No. 4. Radical
prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med
2005;352:1977-84. [PMID: 15888698]
15. American Academy of Family Physicians. Summary of Recommendations
for Clinical Preventive Services, Revision 6.5, March 2008, Order No. 1968.
Leawood, KS: American Academy of Family Physicians; 2007. Accessed at
www.aafp.org. on 17 June 2008.
16. American College of Physicians. Screening for prostate cancer. Ann Intern
Med 1997;126:480-4. [PMID: 9072936]
17. Lim LS, Sherin K. ACPM Prevention Practice Committee. Screening for
prostate cancer in U.S. men ACPM position statement on preventive practice.
Am J Prev Med 2008;34:164-70. [PMID: 18201648]
18. Smith RA, Cokkinides V, Eyre HJ. American Cancer Society guidelines for
the early detection of cancer, 2006. CA Cancer J Clin 2006;56:11-25; quiz
49-50. [PMID: 16449183]
19. American Urological Association. Prostate-specific antigen (PSA) best practice
policy. Oncology (Williston Park) 2000;14:267-72, 277-8, 280 passim.
[PMID: 10736812]
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Members of the U.S. Preventive Services Task Force
Members of the U.S. Preventive Services Task Force* are
Ned Calonge, MD, MPH, Chair (Colorado Department of Public
Health and Environment, Denver, Colorado); Diana B.
Petitti, MD, MPH, Vice Chair (Keck School of Medicine, University
of Southern California, Sierra Madre, California);
Thomas G. DeWitt, MD (Children’s Hospital Medical Center,
Cincinnati, Ohio); Allen J. Dietrich, MD (Dartmouth Medical
School, Lebanon, NH); Kimberly D. Gregory, MD, MPH (Cedars-
Sinai Medical Center, Los Angeles, California); Russell Harris,
MD, MPH (University of North Carolina School of Medicine,
Chapel Hill, North Carolina); George J. Isham, MD, MS
(HealthPartners, Minneapolis, MN); Michael L. LeFevre, MD,
MSPH (University of Missouri School of Medicine, Columbia,
Missouri); Roseanne Leipzig, MD, PhD, (Mount Sinai School of
Medicine, New York, New York): Carol Loveland-Cherry, PhD,
RN (University of Michigan School of Nursing, Ann Arbor,
Michigan); Lucy N. Marion, PhD, RN (Medical College of
Georgia, Augusta, Georgia); Bernadette Melnyk, PhD, RN (Arizona
State College of Nursing and Healthcare Innovation, Phoenix,
Arizona); Virginia A. Moyer, MD, MPH (University of
Texas Health Science Center, Houston, Texas); Judith K. Ockene,
PhD (University of Massachusetts Medical School, Worcester,
Massachusetts); George F. Sawaya, MD (University of California,
San Francisco, San Francisco, California); and Barbara P.
Yawn, MD, MSPH, MSc (Olmsted Medical Center, Rochester,
Minnesota).
*This list includes members of the Task Force at the time
this recommendation was finalized. For a list of current Task
Force members, go to http://www.ahrq.gov/clinic/uspstfab.htm
Disclaimer: Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
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Copyright and Source Information
Source: U.S. Preventive Services Task Force. Screening for Prostate Cancer:
U.S. Preventive Services Task Force
Recommendation Statement. Ann Intern Med 2008;149:185-191.
This document is in the public domain within the United States. For
information on reprinting, contact Randie Siegel, Associate Director, Office of Communications and Knowledge Transfer, Agency for Healthcare Research and Quality,
540 Gaither Road, Rockville, MD 20850.
Requests for linking or to incorporate content in electronic resources
should be sent to: info@ahrq.gov.
AHRQ Publication No. 08-05121-EF-2
Current as of August 2008
Internet Citation:
U.S. Preventive Services Task Force. Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement. AHRQ Publication No. 08-05121-EF-2, August 2008. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/uspstf08/prostate/prostaters.htm