U.S. Preventive Services Task Force
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Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Reprints are available from the USPSTF Web site (http://www.preventiveservices.ahrq.gov).
For a list of Task Force members, see the Appendix.
; Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2008;149:185-191. doi: 10.7326/0003-4819-149-3-200808050-00008
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Published: Ann Intern Med. 2008;149(3):185-191.
Appendix: U.S. Preventive Services Task Force
Update of the 2002 U.S. Preventive Services Task Force (USPSTF) recommendation statement about screening for prostate cancer.
The USPSTF evaluated randomized, controlled trials of the benefits of prostate cancer screening; cohort and cross-sectional studies of the psychological harms of false-positive prostate-specific antigen test results; and evidence on the natural history of prostate-specific antigenâ€“detected prostate cancer to address previously identified gaps in the evidence from the 2002 USPSTF recommendation.
Current evidence is insufficient to assess the balance of benefits and harms of screening for prostate cancer in men younger than age 75 years (I statement).
Do not screen for prostate cancer in men age 75 years or older (Grade D recommendation).
The U.S. Preventive Services Task Force (USPSTF) makes recommendations about preventive care services for patients without recognized signs or symptoms of the target condition.
It bases its recommendations on a systematic review of the evidence of the benefits and harms and an assessment of the net benefit of the service.
The USPSTF recognizes that clinical or policy decisions involve more considerations than this body of evidence alone. Clinicians and policymakers should understand the evidence but individualize decision-making to the specific patient or situation.
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. This is an I statement.
The USPSTF recommends against screening for prostate cancer in men age 75 years or older. This is a grade D recommendation.
See the Figure for a summary of this recommendation and suggestions for clinical practice.
For a summary of the evidence systematically reviewed in making these recommendations, the full recommendation statement (including a summary of research gaps), and supporting documents, please go to http://www.preventiveservices.ahrq.gov.
See Table 1 for a description of the USPSTF grades and Table 2 for a description of the USPSTF classification of levels of certainty about net benefit.
Prostate cancer is the most common nonskin cancer and the second leading cause of cancer death in men in the United States.
The USPSTF found convincing evidence that prostate-specific antigen (PSA) screening can detect some cases of prostate cancer.
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.
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.
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.
This recommendation applies to men in the general U.S. population.
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.
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 cut-points 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 age-adjusted 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).
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.
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).
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).
Shared decision-making resources specific to prostate cancer screening for clinicians and patients are available from the Centers of Disease Control and Prevention (http://www.cdc.gov/cancer/prostate/publications/).
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.
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.
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 update (5) 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 screening-detected prostate cancer who did not receive active treatment.
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).
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).
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.
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).
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.
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 (15), American College of Physicians (16), American College of Preventive Medicine (17), and American Medical Association. The American Cancer Society (18) and American Urological Association (19) recommend offering PSA measurement and digital rectal examination to men annually beginning at age 50 years.
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.
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Krankenhaus Lindenbrunn, Klinik fuer Geriatrie, Lindenbrunn 1, Coppenbruegge 31863, Germany
August 6, 2008
Age cut-offs alone are misleading
The authors define an age cut-off for prostate cancer screening negating this screening for men at age greater 75 years (y) or a life expectancy below 10 y (1). It may be uncertain if screening for prostate cancer using prostate-specific antigen is a useful tool irrespective of age. But an age cut-off of 75 y may be wrong for some men aged 75 y and higher. As Walter and Covinsky (2) reported was the life expectancy for U.S. men in 1997 at age 75 for the top 25th percentile 14,2 y, at age 80 10,8 y and at age 85 7,9 y. For the same age groups the top 50th percentile was 9,3, 6,7 and 4,7 y. In an ageing world (3) it is necessary for clinicians, health care providers and political decision makers to have in mind that aging is different in people with variuos health and functional status. The "best agers" will have a life expectancy of 4.3 y in men and 4.8 y in women (top 25th percentile) at age 95. Summing up biological age alone is a bad adviser for decision making. 1. U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2008;149:185-91. 2. Walter LC, Covinsky KE. Cancer screening in elderly patients. A framework for individualized decision making. JAMA 2001;285:2570-6. 3. Lutz W, Sanderson W, Scherbov S. The coming acceleration of global population aging. Nature 2008;451:716-9. Conflict of Interest:
Badrinath R. Konety
University of California, San Francisco
August 31, 2008
A more nuanced approach to prostate cancer screening
To the Editor:
The USPSTF authors again tackle a difficult subject in updating their recommendations for prostate cancer screening. The most significant change in the new guideline is the grade D recommendation against screening men over the age of 75 years, based on a perceived lack of benefit for prostate cancer treatment in these older men. We would argue, however, that rather than adopting rigid age-based stopping criteria for screening, the medical community should pursue a more nuanced approach to screening, diagnosis, and treatment across age strata.
Screening and potential overdiagnosis of prostate cancer are primarily concerning to the extent that they lead to overtreatment. Overtreatment is certainly a substantial problem among men with low risk prostate cancer, particularly among older men. With cessation of screening among older patients, however, we lose the opportunity to detect aggressive prostate cancer among patients who are in fact most likely to have it. The incidence of high risk prostate cancer in fact increases with age, accounting for 42% of cancers diagnosed in men >75 years vs. 22% among men <75 years. Indeed, as much as overtreatment of low risk disease remains a concern, we have also found evidence of growing underuse of potentially curative local therapy among the men with high risk disease who face the highest risk of disease-specific morbidity and mortality. Rigid age-based criteria, moreover, ignore substantial variation in life expectancy based on overall health and comorbid illnesses.
We have previously attempted to develop multi-specialty consensus recommendations aimed at encouraging a more cautious approach to screening for prostate cancer in men >75 years. During these discussions primary care physicians expressed significant interest in continued screening even in older men and were reluctant to stop screening at a predetermined age. After a yearlong educational campaign, stated physician preferences for continued screening beyond 75 years fell 20%. However the demographic correlates of screeners vs non-screeners did not change: screeners were more likely to be older men themselves.
All patients with mildly elevated PSA on screening tests do not necessarily require further diagnostic evaluation. Likewise, many older men"”likely a substantial majority"”diagnosed with lower risk tumors can be safely followed with active surveillance. Indeed, a greater onus must be placed on physicians (and the men they counsel) to divorce diagnosis from inevitable treatment. Those older men harboring undiagnosed aggressive tumors, however, risk substantial potential morbidity and potential mortality from progressive disease, and should not be denied the opportunity for treatment.
1. Cooperberg MR, Lubeck DP, Meng MV, Mehta SS, Carroll PR: The changing face of low-risk prostate cancer: trends in clinical presentation and primary management. J Clin Oncol 2004; 22: 2141.
2. Konety BR, Cowan JE, Carroll PR; CaPSURE Investigators. Patterns of primary and secondary therapy for prostate cancer in elderly men: analysis of data from CaPSURE. J Urol. 2008;179:1797-804.
3. Cooperberg MR, Cowan J, Broering JM, Carroll PR: High-risk prostate cancer in the United States, 1990-2007. World J Urol 2008; 26: 211.
4. Konety BR, Sharp VJ, Raut H, Williams RD. Screening and management of prostate cancer in elderly men: the Iowa Prostate Cancer Consensus. Urology. 2008;71:511-514.
5. Dall'Era MA, Konety BR, Cowan JE, Shinohara K, Stauf F, Cooperberg MR, Meng MV, Kane CJ, Perez N, Master VA, Carroll PR. Active surveillance for the management of prostate cancer in a contemporary cohort. Cancer 2008;112:2664-2670.
Chair, U.S. Preventive Services Task Force
September 16, 2008
Re: Screening for Prostate Cancer
We appreciate the letters from Drs. Konety and Gogol regarding the U.S. Preventive Service Task Force's (USPSTF) updated recommendation on screening for prostate cancer. (1) The USPSTF recommended against screening men age 75 years and older.
It is important to emphasize first that a systematic review conducted in collaboration with the USPSTF (2) identified no direct evidence (i.e. evidence from randomized trials) that permitted the USPSTF to determine whether prostate-specific antigen (PSA) screening has a net benefit on mortality for men of any age. While some men may benefit from earlier detection of potentially fatal prostate cancers, others will be harmed by the adverse effects of detection and treatment of abnormal-appearing prostate cells that would never have caused clinical symptoms. We will not know if the uncontrolled experiment of screening millions of men for prostate cancer that began in the early 1990s has, on the whole, increased life-expectancy or shortened it until ongoing randomized trials are completed.
In concluding with moderate certainty that the harms of screening men age 75 years and older outweigh the benefits, the USPSTF relied on information about the natural history of clinically-detected prostate cancer from a randomized trial comparing the outcomes of radical prostatectomy and watchful waiting. (3) This trial suggested that the length of time required to experience a mortality benefit from PSA screening is greater than ten years. Even assuming that every prostate cancer detected by screening is potentially fatal (not true) and that treatments are never fatal (also not true), the majority of men age 75 years and older would experience no benefits from screening.
Recently published data from the Bill-Axelson trial (4) suggests that the USPSTF may have set the screening "cutoff" age conservatively. Men in the trial over age 65 years who underwent prostatectomy had the same mortality rate as men who did not. (4)
Dr. Konety asserts that older men diagnosed with "low risk" prostate cancer could choose to enter active surveillance rather than undergo treatment, thus reducing the harms associated with prostate cancer screening. In practice, potentially lethal prostate cancers cannot be reliably identified. Because of the desire of most men to remove all traces of cancer, attrition rates from studies of active surveillance have been high, rendering the effectiveness of the surveillance protocol uninterpretable. (2) In addition, there is no evidence that active surveillance itself leads to more benefits than harms.
1. 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.
2. 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;149:192-199.
3. Bill-Axelson A, Holmberg L, Ruutu M, Haggman 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;352:1977-1984.
4. Bill-Axelson A, Holmberg L, Filen F, Ruutu M, Garmo H, Busch C, et al. Scandinavian Prostate Cancer Group Study No. 4. Radical prostatectomy versus watchful waiting in early prostate cancer: the Scandinavian prostate cancer group-4 randomized trial. J Natl Cancer Inst 2008;100:1144 -1154.
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