Influence of Study Features and Methods on Overdiagnosis Estimates in Breast and Prostate Cancer Screening
Tara Parker-Pope answers some of the most common questions about P.S.A. testing and what the task force recommendations mean for men.
Mostrando las entradas con la etiqueta Prostate. Mostrar todas las entradas
Mostrando las entradas con la etiqueta Prostate. Mostrar todas las entradas
11 junio, 2013
Influence of Study Features and Methods on Overdiagnosis Estimates in Breast and Prostate Cancer Screening
02 junio, 2013
Screening for prostate cancer
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| English: Prostate and bladder, sagittal section. 中文: 前列腺與膀胱，矢狀切面。 (Photo credit: Wikipedia) |
Expanding the evidence on cancer screening: the value of scientific, social and ethical perspectives: Lucie Rychetnik, Stacy M Carter, Alexandra Barratt and Les Irwig. Med J Aust 2013; 198 (10): 536-539. doi: 10.5694/mja12.11275
United State American Task Force for Preventive Guidelines
Canadian Task Force on Preventive Health Care ( CTFPHC )
American Urological Association
13 mayo, 2013
Information for primary care: PSA testing in asymptomatic men (evidence document
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| A light blue ribbon is the symbol for prostate cancer (Photo credit: Wikipedia) |
Source: http://www.cancerscreening.nhs.uk
Information for primary care: PSA testing in asymptomatic men (evidence document)
Published January 2010
PDF Format (670Kb)
The information booklet PSA Testing in Asymptomatic Men was designed to help primary care teams to provide asymptomatic men with information on the prostate-specific antigen (PSA) test for prostate cancer.
This version of the booklet has been produced to provide exactly the same information, but also gives primary care teams details of the evidence on which that information is based.
Download Document
prostate cancer.pdf (654 KB)
08 octubre, 2011
PSA and prostate cancer
Image via WikipediaDraft Recommendation Statement
The U.S. Preventive Services Task Force will be accepting comments on this draft recommendation statement beginning on Tuesday, October 11, 2011.
The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific clinical preventive services for patients without related signs or symptoms.
It bases its recommendations on the evidence of both the benefits and harms of the service, and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.
The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.
Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement
DRAFT
Summary of Recommendation and Evidence
The U.S. Preventive Services Task Force (USPSTF) recommends against prostate-specific antigen (PSA)-based screening for prostate cancer.This is a grade D recommendation.
This recommendation applies to men in the U.S. population that do not have symptoms that are highly suspicious for prostate cancer, regardless of age, race, or family history. The Task Force did not evaluate the use of the PSA test as part of a diagnostic strategy in men with symptoms that are highly suspicious for prostate cancer. This recommendation also does not consider the use of the PSA test for surveillance after diagnosis and/or treatment of prostate cancer.
Rationale
Importance
Prostate cancer is the most commonly diagnosed nonskin cancer in men in the United States, with a lifetime risk of diagnosis currently estimated at 15.9%. Most cases of prostate cancer have a good prognosis, but some are aggressive; the lifetime risk of dying from prostate cancer is 2.8%. Prostate cancer is rare before age 50 years and very few men die of prostate cancer before age 60 years. The majority of deaths due to prostate cancer occur after age 75 years (1).
Detection
Contemporary recommendations for prostate cancer screening all incorporate the measurement of serum PSA levels; other methods of detection such as digital rectal examination or ultrasonography may be included. The evidence is convincing that PSA-based screening programs result in the detection of many cases of asymptomatic prostate cancer. The evidence is also convincing that the majority of men who have asymptomatic cancer detected by PSA screening have a tumor that meets histological criteria for prostate cancer, but the tumor either will not progress or is so indolent and slow-growing that it will not affect the man’s lifespan or cause adverse health effects, as he will die of another cause first. The terms “overdiagnosis” or “pseudodisease” are used to describe both of these situations. It is difficult to determine the precise magnitude of overdiagnosis associated with any screening and treatment program. The rate of overdiagnosis of prostate cancer increases as the number of men subjected to biopsy increases. The number of cancer cases that could be detected in a screened population is large; a single study in which men eligible for PSA screening underwent biopsy irrespective of PSA level detected cancer in nearly 25% of men (2). The rate of overdiagnosis will also depend upon the age at which diagnosis is made. Cancer diagnosis in older men with shorter life expectancies is much more likely to be overdiagnosis.
Benefits of Detection and Early Intervention
The primary goal of prostate cancer screening is to reduce deaths due to prostate cancer, and a reduction in either prostate cancer death or overall mortality was the primary outcome addressed in all prostate cancer screening studies assessed by the Task Force. The evidence is convincing that for men aged 70 years and older, screening has no mortality benefit. For men aged 50 to 69 years, the evidence is convincing that the reduction in prostate cancer mortality 10 years after screening is small to none. Screen-detected cancer can fall into one of three categories: cancer that results in death in spite of early diagnosis and treatment, cancer for which early diagnosis and treatment improves survival, and cancer for which the outcome would be good in the absence of screening due to indolent tumors. Ninety-five percent of men with PSA-detected cancer who are followed for 12 years do not die from that cancer, even in the absence of definitive treatment (3). The possibility is very small that death from prostate cancer is less likely in men whose prostate cancer is detected by PSA screening rather than waiting for clinical detection, and the time to any potential benefit is long. No prostate cancer screening study, individually or combined with other screening studies, or study of treatment of screen-detected cancer, has demonstrated a reduction in all-cause mortality.
07 octubre, 2011
PSA & New York Times
Healthy men should no longer receive a P.S.A. blood test to screen forprostate cancer because the test does not save lives over all and often leads to more tests and treatments that needlessly cause pain,impotence and incontinence in many, a key government health panel has decided.
Image via WikipediaThe draft recommendation, by the United States Preventive Services Task Force and due for official release next week, is based on the results of five well-controlled clinical trials and could substantially change the care given to men 50 and older. There are 44 million such men in the United States, and 33 million of them have already had a P.S.A. test — sometimes without their knowledge — during routine physicals.
The task force’s recommendations are followed by most medical groups. Two years ago the task force recommended that women in their 40s should no longer get routine mammograms, setting off a firestorm of controversy. The recommendation to avoid the P.S.A. test is even more forceful and applies to healthy men of all ages.
“Unfortunately, the evidence now shows that this test does not save men’s lives,” said Dr. Virginia Moyer, a professor of pediatrics at Baylor College of Medicine and chairwoman of the task force. “This test cannot tell the difference between cancers that will and will not affect a man during his natural lifetime. We need to find one that does.”
But advocates for those with prostate cancer promised to fight the recommendation. Baseball’s Joe Torre, the financier Michael Milken and Rudolph W. Giuliani, the former New York City mayor, are among tens of thousands of men who believe a P.S.A. test saved their lives.
The task force can also expect resistance from some drug makers and doctors. Treating men with high P.S.A. levels has become a lucrative business. Some in Congress have criticized previous decisions by the task force as akin to rationing, although the task force does not consider cost in its recommendations.
“We’re disappointed,” said Thomas Kirk, of Us TOO, the nation’s largest advocacy group for prostate cancer survivors. “The bottom line is that this is the best test we have, and the answer can’t be, ‘Don’t get tested.’ ”
But that is exactly what the task force is recommending. There is no evidence that a digital rectal exam or ultrasound are effective, either. “There are no reliable signs or symptoms of prostate cancer,” said Dr. Timothy J. Wilt, a member of the task force and a professor of medicine at the University of Minnesota. Frequency and urgency of urinating are poor indicators of disease, since the cause is often benign.
The P.S.A. test, routinely given to men 50 and older, measures a protein — prostate-specific antigen — that is released by prostate cells, and there is little doubt that it helps identify the presence of cancerous cells in the prostate. But a vast majority of men with such cells never suffer ill effects because their cancer is usually slow-growing. Even for men who do have fast-growing cancer, the P.S.A. test may not save them since there is no proven benefit to earlier treatment of such invasive disease.
As the P.S.A. test has grown in popularity, the devastating consequences of the biopsies and treatments that often flow from the test have become increasingly apparent. From 1986 through 2005, one million men received surgery, radiation therapy or both who would not have been treated without a P.S.A. test, according to the task force. Among them, at least 5,000 died soon after surgery and 10,000 to 70,000 suffered serious complications. Half had persistent blood in their semen, and 200,000 to 300,000 suffered impotence, incontinence or both. As a result of these complications, the man who developed the test, Dr. Richard J. Ablin, has called its widespread use a “public health disaster.”
One in six men in the United States will eventually be found to have prostate cancer, making it the second most common form of cancer in men after skin cancer. An estimated 32,050 men died of prostate cancer last year and 217,730 men received the diagnosis. The disease is rare before age 50, and most deaths occur after age 75.
Not knowing what is going on with one’s prostate may be the best course, since few men live happily with the knowledge that one of their organs is cancerous. Autopsy studies show that a third of men ages 40 to 60 have prostate cancer, a share that grows to three-fourths after age 85.
P.S.A. testing is most common in men over 70, and it is in that group that it is the most dangerous since such men usually have cancerous prostate cells but benefit the least from surgery and radiation. Some doctors treat patients who have high P.S.A. levels with drugs that block male hormones, although there is no convincing evidence that these drugs are helpful in localized prostate cancer and they often result in impotence, breast enlargement and hot flashes.
Of the trials conducted to assess the value of P.S.A. testing, the two largest were conducted in Europe and the United States. Both “demonstrate that if any benefit does exist, it is very small after 10 years,” according to the task force’s draft recommendation statement.
The European trial had 182,000 men from seven countries who either got P.S.A. testing or did not. When measured across all of the men in the study, P.S.A. testing did not cut death rates in nine years of follow-up. But in men ages 55 to 69, there was a very slight improvement in mortality. The American trial, with 76,693 men, found that P.S.A. testing did not cut death rates after 10 years.
Dr. Eric Klein of the Cleveland Clinic, an expert in prostate cancer, said he disagreed with the task force’s recommendations. Citing the European trial, he said “I think there’s a substantial amount of evidence from randomized clinical trials that show that among younger men, under 65, screening saves lives.”
The task force’s recommendations apply only to healthy men without symptoms. The group did not consider whether the test is appropriate in men who already have suspicious symptoms or those who have already been treated for the disease. The recommendations will be open to public comment next week before they are finalized.
Recommendations of the task force often determine whether federal health programs likeMedicare and private health plans envisioned under the health reform law pay fully for a test. But legislation already requires Medicare to pay for P.S.A. testing no matter what the task force recommends.
Still, the recommendations will most likely be greeted with trepidation by the Obama administration, which has faced charges from Republicans that it supports rationing of health care services, which have been politically effective, regardless of the facts.
After the task force’s recommendation against routine mammograms for women under 50, Health and Human Services Secretary Kathleen Sibelius announced that the government would continue to pay for the test for women in their 40s. On Thursday, the administration announced with great fanfare that as a result of the health reform law, more people with Medicare were getting free preventive services like mammograms.
Dr. Michael Rawlins, chairman of the National Institute for Health and Clinical Excellence in Britain, said he was given a P.S.A. test several years ago without his knowledge. He then had a biopsy, which turned out to be negative. But if cancer had been detected, he would have faced an awful choice, he said: “Would I want to have it removed, or would I have gone for watchful waiting with all the anxieties of that?” He said he no longer gets the test.
But Dan Zenka, a spokesman for the Prostate Cancer Foundation, said a high P.S.A. test result eventually led him to have his prostate removed, a procedure that led to the discovery that cancer had spread to his lymph nodes. His organization supports widespread P.S.A. testing. “I can tell you it saved my life,” he said.
05 octubre, 2011
Cribado de cancer de prostata - Screening of prostaste cancer
Image via WikipediaIn the United States, most men over the age of 50 years have had a prostate-specific–antigen (PSA) test,1 despite the absence of evidence from large, randomized trials of a net benefit. Moreover, about 95% of male urologists and 78% of primary care physicians who are 50 years of age or older report that they have had a PSA test themselves,2 a finding that suggests they are practicing what they preach. And indeed, U.S. death rates from prostate cancer have fallen about 4% per year since 1992, five years after the introduction of PSA testing.3 Perhaps the answer to the PSA controversy is already staring us in the face. At the same time, practice guidelines cite the unproven benefit of PSA screening, as well as the known side effects,4,5 which largely reflect the high risks of overdiagnosis and overtreatment that PSA-based screening engenders.6
The first reports from two large, randomized trials that many observers hoped would settle the controversy appear in this issue of the Journal. In the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, Andriole et al.7 report no mortality benefit from combined screening with PSA testing and digital rectal examination during a median follow-up of 11 years.8 In the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, Schröder et al.8 report that PSA screening without digital rectal examination was associated with a 20% relative reduction in the death rate from prostate cancer at a median follow-up of 9 years, with an absolute reduction of about 7 prostate cancer deaths per 10,000 men screened.8 The designs of the two trials are different and provide complementary insights.
First, one must ask, "Why were these results published now?" Neither set of findings seems definitive; that is, there was neither a clear declaration of futility in the PLCO trial nor an unambiguous net benefit in the ERSPC trial. Both studies are ongoing, with future updates promised. The report on the ERSPC trial follows a third planned interim analysis, which found a marginally significant decrease in prostate-cancer mortality after adjustment of the P value for the two previous looks in an attempt to avoid a false positive conclusion (yet apparently preserving no alpha for the planned final analysis). On the other hand, the investigators in the PLCO trial made the decision to publish their results now because of concern about the emerging evidence of net harm compared with potential benefits associated with PSA screening. Both decisions to publish now can be criticized as premature, leaving clinicians and patients to deal with the ambiguity.
The ERSPC trial is actually a collection of trials in different countries with different eligibility criteria, randomization schemes, and strategies for screening and follow-up. The report by Schröder et al. is based on a predefined core group of men between 55 and 69 years of age at study entry. Subjects were generally screened every 4 years, and 82% were screened at least once. Contamination of the control group with screening as part of usual care is not described. Biopsies were generally recommended for subjects with PSA levels of more than 3.0 ng per milliliter. It is unclear whether the clinicians and hospitals treating patients with prostate cancer differed between the two study groups.
Adjudications of causes of death were made by committees whose members were unaware of study-group assignments, though not of treatments. This point is important, since previous research has suggested that the cause of death is less likely to be attributed to prostate cancer among men receiving attempted curative treatment.9 Misattribution might then create a bias toward screening, since the diagnosis of more early-stage cancers in the ERSPC trial led to substantially more attempted curative treatments.
The ERSPC interim analysis revealed a 20% reduction in prostate-cancer mortality; the adjusted P value was 0.04. The estimated absolute reduction in prostate-cancer mortality of about 7 deaths per 10,000 men after 9 years of follow-up, if real and not the result of chance or bias, must be weighed against the additional interventions and burdens. The 73,000 men in the screening group underwent more than 17,000 biopsies, undoubtedly many more than did men in the control group, though the latter is not reported. Men had a substantially higher cumulative risk of receiving the diagnosis of prostate cancer in the screening group than in the control group (820 vs. 480 per 10,000 men). Diagnosis led to more treatment, with 277 versus 100 per 10,000 men undergoing radical prostatectomy and 220 versus 123 per 10,000 undergoing radiation therapy with or without hormones, respectively (tentative estimates given the unknown treatments in both groups).
Although estimates of the benefit of screening were somewhat greater for men who actually underwent testing (taking into account noncompliance) than for those who were not tested, the side effects would be proportionately higher as well. Given these trade-offs, the promise of future ERSPC analyses addressing quality of life and cost-effectiveness is welcome indeed. The ERSPC results also reemphasize the need for caution in screening men over the age of 69 years, given an early trend toward higher prostate-cancer mortality with screening in this age subgroup, although this finding may well be due to chance alone.
A final point to make about the ERSPC trial is that to the extent that the diagnosis and treatment of prostate cancer in the screening group differed from those in the control group, it becomes difficult to dissect out the benefit attributable to screening versus improved treatment once prostate cancer was suspected or diagnosed. A similar distribution of treatments among seemingly similar patients with cancer is only partially reassuring in this regard.
Despite a longer median follow-up, the PLCO trial was smaller and therefore less mature than the ERSPC trial, with 174 prostate-cancer deaths driving the power of the study, as compared with 540 such deaths in the ERSPC trial. The screening protocol was homogeneous across sites with an enrollment age of 55 to 74 years and annual PSA tests for 6 years and digital rectal examinations for 4 years, with about 85% compliance. Subjects in the screening group who had a suspicious digital rectal examination or a PSA level of more than 4.0 ng per milliliter received a recommendation for further evaluation. This strategy helped to ensure that any difference in outcome was attributable to screening, rather than downstream management. The effectiveness of screening, of course, will be determined by the effectiveness of subsequent "usual care," but this is the same usual care that many practitioners assume has been responsible for the falling U.S. death rate from prostate cancer. Adjudication of causes of death was similar to that in the ERSPC trial.
Though the PLCO trial has shown no significant effect on prostate-cancer mortality to date, the relatively low number of end points begets a wide confidence interval, which includes at its lower margin the point estimate of effect from the ERSPC trial. Other likely explanations for the negative findings are high levels of prescreening in the PLCO population and contamination of the control group. Contamination was assessed by periodic cross-sectional surveys, with about half the subjects in the control group undergoing PSA testing by year 5. It is unclear whether these estimates reflect testing that year or since trial inception; if the former, the cumulative incidence may be even higher. The smaller difference in screening intensity between the two study groups in the PLCO trial, as compared with the ERSPC trial, is reflected in a smaller risk of overdiagnosis (23% vs. more than 70%) and a less impressive shift in cancer stage and grade distributions. Given that study-group contamination from the use of digital rectal examination was less problematic (only about 25%), ongoing results from both of these trials may necessitate rethinking the role of digital rectal examination in cancer screening.
After digesting these reports, where do we stand regarding the PSA controversy? Serial PSA screening has at best a modest effect on prostate-cancer mortality during the first decade of follow-up. This benefit comes at the cost of substantial overdiagnosis and overtreatment. It is important to remember that the key question is not whether PSA screening is effective but whether it does more good than harm. For this reason, comparisons of the ERSPC estimates of the effectiveness of PSA screening with, for example, the similarly modest effectiveness of breast-cancer screening cannot be made without simultaneously appreciating the much higher risks of overdiagnosis and overtreatment associated with PSA screening.
The report on the ERSPC trial appropriately notes that 1410 men would need to be offered screening and an additional 48 would need to be treated to prevent one prostate-cancer death during a 10-year period, assuming the point estimate is correct. And although the PLCO trial may not have the power as yet to detect a similarly modest benefit of screening, its power is already more than adequate to detect important harm through overdiagnosis. However, the implications of the trade-offs reflected in these data, like beauty, will be in the eye of the beholder. Some well-informed clinicians and patients will still see these trade-offs as favorable; others will see them as unfavorable. As a result, a shared decision-making approach to PSA screening, as recommended by most guidelines, seems more appropriate than ever.
Finally, despite these critiques, both groups of investigators deserve high praise for their persistence and perseverance: to manage such monstrous trials is a herculean task, made no easier when so many observers think the results are self-evident. Further analyses will be needed from these trials, as well as from others — such as the Prostate Cancer Intervention Versus Observation Trial (PIVOT) in the United States (ClinicalTrials.gov number, NCT00007644 [ClinicalTrials.gov] )10 and the Prostate Testing for Cancer and Treatment (PROTECT) trial in the United Kingdom (Current Controlled Trials number, ISRCTN20141297 [controlled-trials.com] )11 — if the PSA controversy is finally to sleep the big sleep.
No potential conflict of interest relevant to this article was reported.
Source Information
From Massachusetts General Hospital and Harvard Medical School, Boston.
This article (10.1056/NEJMe0901166) was published at NEJM.org on March 18, 2009.
References
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- Ries LAG, Melbert D, Krapcho M, et al. SEER cancer statistics review, 1975–2005. Bethesda, MD: National Cancer Institute, 2008. (Accessed March 6, 2009 at http://seer.cancer.gov/csr/1975_2005/.)
- Smith RA, Cokkinides V, Brawley OW. Cancer screening in the United States, 2008: a review of current American Cancer Society guidelines and cancer screening issues. CA Cancer J Clin 2008;58:161-179.
[Free Full Text] - 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.
[Free Full Text] - Barry MJ. Why are a high overdiagnosis probability and a long lead time for prostate cancer screening so important? J Natl Cancer Inst (in press).
- Andriole GL, Grubb RL III, Buys SS, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310-1319.
[Free Full Text] - Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320-1328.
[Free Full Text] - Newschaffer CJ, Otani K, McDonald MK, Penberthy LT. Causes of death in elderly prostate cancer patients and in a comparison nonprostate cancer cohort. J Natl Cancer Inst 2000;92:613-621.
[Free Full Text] - Wilt TJ, Brawer MK, Barry MJ, et al. The Prostate cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy to watchful waiting for men with clinically localized prostate cancer. Contemp Clin Trials 2009;30:81-87. [CrossRef][ISI][Medline]
- Donovan J, Hamdy F, Neal D, et al. Prostate Testing for Cancer and Treatment (ProtecT) feasibility study. Health Technol Assess 2003;7:1-88. [Medline]
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