Fulfilling the Potential of Cancer Prevention and Early Detection (2003) / Chapter Skim
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5. Potential of Screening to Reduce the Burden of Cancer
5. Potential of Screening to Reduce the Burden of Cancer
Pages 156-223
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From page 156... ...
. Some investigators draw a distinction between screening and case finding, using the former term to describe population-based screening programs, such as those conducted at health fairs or shopping malls, and the latter term to refer to testing of patients in the clinical setting.
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From page 157... ...
. Chapter 6 examines strategies for optimization of the delivery of recommended cancer screening tests from the perspective of the health care system, providers, and, most importantly, the patient.
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From page 158... ...
A common criticism of screening for prostate cancer, for example, is that many of the cancers detected by screening are latent carcinomas that, due to that disease's slow growth characteristics, are unlikely to progress or cause clinical symptoms (Woolf, 1995~. Screening mammography has led to increased detection of ductal carcinoma in situ (Feig, 2000; Winchester et al., 2000)
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From page 159... ...
Although the sensitivity and specificity of a cancer screening test are generally constant across populations and settings, this is not true for the positive predictive value (PPV) , which is the probability that an abnormal
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From page 160... ...
(Table 5.1~. The policy significance of these mathematics is that, regardless of the accuracy of a screening test, the administration of a test to populations or individuals with a low risk of cancer has TABLE 5.1 Illustration of Influence of Prevalence on Positive Predictive Value Prevalence = 1 percent, sensitivity = 90 percent, specificity = 90 percent No.
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From page 161... ...
. Effectiveness of Early Detection A common mistake in determining whether screening for cancer is justified and a reason for premature enthusiasm for promoting screening tests is to limit consideration to the issues described above: burden of suffering and accuracy.
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From page 162... ...
Although little harm would have occurred if the cancer went undetected, the excellent outcomes of screening programs that predominantly detect such lesions are often cited as evidence of the benefits of screening. These principles are embodied in Whitmore's now-famous aphorism about prostate cancer: "Is cure possible for those for whom it is necessary, and is cure necessary for those in whom it is possible?
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From page 163... ...
Patients diagnosed earlier can seem to live longer after diagnosis even if the time that they die does not change. For illustration, consider a man who is destined to develop symptoms from prostate cancer at age 65 and to die at age 70.
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From page 164... ...
One analysis, based on certain assumptions of efficacy, estimated that lifetime screening for breast cancer from age 50 until death results in a maximum potential life expectancy gain of 43 days, whereas the cessation of screening at age 75 or 80 would result in women giving up a maximum potential life expectancy gain of 9 or 5 days, respectively (Rich and Black, 20001. Rather than relying on such modeling data, which have their limitations, it would be preferable to examine direct evidence of the relative benefits of screening with advancing age, but most screening trials have limited enrollment to patients under the ages of 70, limiting access to definitive data.
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From page 165... ...
Unless the decision to screen patients is made randomly, it is possible that screened and unscreened persons differ in characteristics other than screening that may account, at least in part, for the observed outcomes. It is this concern that accounts for the primacy of randomized controlled trials in demonstrating the effectiveness of screening (Tadad, 1998~.
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From page 166... ...
If that probability is 100/100,000 over some defined interval of time, the intervention reduces the risk of death to 80/100,000, an absolute difference of 20/ 100,000 or an absolute risk reduction of 0.02 percent, a far less impressive figure than the relative risk reduction of 20 percent. Although both figures are true, the absolute risk reduction has important policy implications, because it indicates that a large number of people must receive the intervention to save the life of one individual.
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From page 167... ...
They do not stipulate the health outcome prevented two screening tests can have the same NNS, with, for example, one saving lives and the other one preventing fractures nor do they address the harms and costs of interventions. In the context of screening, however, this measure can help place in context the size of the populations that do and do not benefit from early detection (Rembold, 1998~.
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From page 168... ...
For example, as discussed later in this chapter, some studies of women who have received false-positive mammography results reveal continued anxiety on long-term follow-up, well after biopsies have shown no breast cancer. These concerns, as well as ethical and legal ramifications, become more intense in the context of emerging technologies that screen for genetic susceptibility to cancer.
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From page 169... ...
Patients may mistakenly assume that they are no longer in need of repeat screening at recommended intervals or that the clean bill of health makes it unnecessary to engage in other preventive behaviors or to seek clinical attention for abnormal signs or symptoms. Arguing against routine screening for lung cancer, Frame wrote: "A significant potential harm of screening is that smokers will interpret negative results of screening tests as assurance that they are disease free and will be less motivated to quit smoking" (Frame, 2000, p.
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From page 170... ...
A screening test can be more or )
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From page 171... ...
Estimates of the cost-effectiveness of health services, cancer screening tests included, often vary widely because of differences in how the analyses were approached. Trade-Offs and Shared Decision Making Responsible decisions about whether cancer screening is appropriate require a methodical weighing of benefits and harms to determine whether the screened population gains more than it loses through screening.
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From page 172... ...
Studies show that patients given the same facts about four colorectal cancer screening tests make different choices about which option is best (Leard et al., 1997; Pignone et al., 1999~. When the best choice depends highly on personal preferences that vary substantially in the population, groups that issue uniform guidelines for or against screening expose a sizable proportion of the population to the wrong choice (Woolf, 1997a)
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From page 173... ...
) or to understand relative or absolute risk reductions when they were applied to their perceived risk of breast cancer (Schwartz et al., 1997~.
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From page 174... ...
EFFECTIVENESS OF CANCER SCREENING The remainder of this chapter focuses on four cancers for which there is a large body of evidence regarding the effectiveness of routine screening, including three cancers that are among the leading causes of cancer deaths in the United States: breast, colorectal, and prostate cancer. The review also examines cervical cancer, which claims fewer lives but for which important evidence and screening guidelines are available.
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From page 175... ...
Co~orecta} Cancer The colorectal screening tests considered in the review in this part of the chapter are the fecal occult blood test (FOBT) , flexible sigmoidoscopy, double-contrast barium enema, and colonoscopy.
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From page 176... ...
In screening trials, a program of FOBT every 1 to 2 years has been reported to detect 72 to 92 percent of colorectal cancers (Hart/castle et al., 1996; Kronborg et al., 1996; Mande!
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From page 177... ...
, and Denmark (Kronborg et al., 1996) have demonstrated that a program of annual or biennial screening by home FOBT reduces the rate of mortality from colorectal cancer by 15 to 33 percent (Table 5.2~.
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From page 178... ...
studies have demonstrated, however, that patients who die of colorectal cancer are significantly less likely than matched controls to have undergone sigmoidoscopy (Muller and Sonnenberg, 1995; Newcomb et al., 1992; Selby et al., 1992~. To address concerns that confounding variables might account for this observation, Selby and colleagues (1992)
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From page 179... ...
Barium Enema Data regarding the accuracy of barium enema for the detection of polyps and colon cancer in asymptomatic screened populations are limited. Studies that were poorly designed to assess test accuracy report sensitivities of 70 to 90 percent for the detection of polyps larger than 1 cm and 55 to 85 percent for the detection of colorectal cancer and specificities of 90 to 95 percent and 99 percent, respectively (Winawer et al., 1997~.
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From page 180... ...
Colonoscopy screening is routinely advocated for patients with a family history of familial polyposis syndrome and hereditary nonpolyposis colorectal cancer or for patients with inflammatory bowel disease. Controlled observational studies suggest that such screening improves survival from familial polyposis syndrome, a hereditary syndrome associated with an extremely high risk of colorectal cancer (Heiskanen et al., 2000~.
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From page 181... ...
Calculations of the cost-effectiveness of screening for colorectal cancer are highly sensitive to certain assumptions, such as the time assumed to evolve from polyps to cancer and the performance characteristics of tests. Thus, individual reports often reach different conclusions about which test or which combination of tests is most cost-effective.
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From page 182... ...
.. and risks ot the tour screening tests tor colorectal cancer.
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From page 183... ...
The informational intervention group demonstrated a more accurate understanding of the PPV, but those receiving the absolute risk information rated efficacy lower than did those who received relative risk information; controls rated efficacy highest (Wolf and Schorling, 2000~. Current Guidelines Most organizations are in agreement that all Americans age 50 and older should be periodically screened for colorectal cancer and should be allowed to choose from options that include FOBT, flexible sigmoidoscopy, colonoscopy, or double-contrast barium enema (see Box 5.3 for guidelines published since 1996~.
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From page 185... ...
Guidelines for surveillance of persons with previously diagnosed polyps or colorectal cancer have also been disseminated but fall outside the scope of this review. Breast Cancer The screening tests reviewed here include clinical breast examination, mammography, screening for mutations in BRCA1 and BRCA2 (mutations of breast cancer-associated tumor suppressor genes)
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From page 186... ...
Clinical breast examination was estimated to detect 3 to 45 percent of breast cancers that screening mammography missed (Barton et al., 1999~. A sensitivity of 59 percent and a specificity of 93 percent were recently reported in an evaluation of 752,000 clinical breast examinations (Bobo et al., 2000~.
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From page 187... ...
Mammography Because several clinical trials combined screening mammography with clinical breast examination, the performance characteristics of mammography in isolation are uncertain. The sensitivity, specificity, and PPV reported by trials that examined mammography alone are 68 to 88,95 to 98, and 4 to 22 percent, respectively (Fletcher et al., 1993~.
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From page 188... ...
In a Canadian trial, the rates of false positivity for the combination of screening mammography and clinical breast examination were 7 to 10 percent for women ages 40 to 49 and 5 to 8 percent for women ages 50 to 59 (Miller et al., 1992a,b)
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From page 189... ...
Most reported that screening mammography reduced the risk of death from breast cancer, with relative risk reductions ranging from 3 to 32 percent. The relative risk reduction achieved statistical significance in only a few trials, but the combined data from all trials show a highly significant reduced risk.
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From page 190... ...
showed no effect on breast cancer mortality (pooled relative risk, 1.04; 95 percent CI, 0.84 to 1.27~. The investigators concluded that screening mammography is unjustified, generating a flurry of broadcast and print media reports in early 2002 questioning the merits of mammography and prompting an announcement by the National Cancer Institute PDQ advisory pane!
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From page 191... ...
Even with a relative risk reduction of 20-25 percent, large numbers of women (perhaps 1,000) must be screened to prevent a single death from breast cancer, raising a legitimate question about whether the benefit is of sufficient magnitude to outweigh potential harms (see below)
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From page 192... ...
The only trial designed specifically to evaluate screening for women ages 40 to 49 was the Canadian National Breast Screening Study. That randomized trial, which assessed the effectiveness of the combination of annual mammography, physical breast examination, and teaching of breast self-examination, initially reported a relative risk ratio of 1.36 (95 percent CI, 0.84 to 2.21)
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From page 193... ...
Whether the existing evidence is sufficient to justify routine screening mammography for women ages 40 to 49 has long been a matter of debate (Smith, 2000~. Beyond concerns about statistical significance, some question the absolute benefit of screening, given the low prevalence of breast cancer in premenopausal women.
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From page 194... ...
The limited number of women of this age in the trials gave the trials inadequate power to conclude whether the difference in relative risk reduction between annual and less frequent screening is statistically significant. Indirect evidence suggests that annual screening might significantly lower the rate of mortality from breast cancer (Feig, 1995)
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From page 195... ...
There remains little direct evidence that breast self-examination improves the outcomes from breast cancer. A nonrandomized study in the United Kingdom found that two centers at which women were invited to education sessions on breast self-examination had combined mortality rates that were similar to those at control centers, but one of the two centers did have significantly lower death rates (Lancet, 1999~.
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From page 196... ...
, surveys suggest that after receiving a false-positive result women experience increased anxiety at both short-term and long-term follow-ups and experience added stress when they undergo biopsy (Gilbert et al., 1998; Gram et al., 1990; Lerman et al., 1991b; Lowe et al., 1999; Olsson et al., 1999~. In one survey, 41 to 47 percent of women with suspicious mammograms expressed anxiety and worry about breast cancer (Lerman et al., 1991b)
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From page 197... ...
(Kerlikowske et al., 1993~. There is no direct evidence that ionizing radiation from mammography causes breast cancer.
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From page 198... ...
The ripple effects of genetic testing for mutations in the BRCA1 and BRCA2 genes pose formidable challenges to the physician attempting to offer patients informed consent before undergoing such testing (MiesfelUt et al., 2000~. Cost-Effectiveness A review of economic evaluations of breast cancer screening published through 1997 found that estimates ranged widely.
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From page 199... ...
For some time the argument centered on statistical significance because no individual trial or meta-analysis could exclude the possibility that lower mortality rates in that age group were due to chance. The extended follow-up data now available has convinced most analysts that mammography reduces breast cancer mortality in women ages 40 to 49 as well.
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From page 200... ...
convened in 1997 by the National Institutes of Health, faced with this evidence, concluded that it was inappropriate to issue a uniform recommendation for all women ages 40 to 49. Instead, it recognized the diversity of women's views and recommended that the choice be individualized for each woman on the basis of "how she perceives and weighs each potential risk and benefit, the values the woman places on each, and how she deals with uncertainty" (National Institutes of Health, 1997, p.1015~.
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From page 201... ...
The success with which the language used in recent prostate cancer screening guidelines has clarified this role is discussed in the next section of this chapter. Increasingly evident in the years since the consensus conference is that the risk of breast cancer is not a dichotomous variable in which the need for
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From page 202... ...
If the appropriateness of screening mammography in a 48-year-old women depends on how she weighs the NNS against the risk of a falsepositive result, the same is true of a 52-year-old woman; it is only the ratios, and not the need for value judgments, that change with time. As Smith advocated, rather than continuing to focus on women ages 40 to 49 as a distinct cohort, "an alternative and more productive view is that women of all ages need to be fully informed about the benefits and limitations of breast cancer screening" (Smith, 2000, p.
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From page 203... ...
Other subcommittees will focus on the basic biology of early breast cancers, and new technologies and molecular methods to advance early detection. Box 5.4 summarizes selected recommendations for breast cancer screen.
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From page 205... ...
The digital rectal examination has a PPV of 15 to 30 percent and a sensitivity of approximately 60 percent. There is little evidence that digital rectal examinations reduce the rate of mortality from prostate cancer.
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From page 206... ...
was 9.7 percent. It was estimated that only 37 percent of prostate cancers were diagnosed by using a cutoff PSA level of 2 to 4 ng/m!
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From page 207... ...
before their prostate cancers progress to clinical significance or metastasize. There are methodological challenges to ascertaining the true cause of death of men with prostate cancer (Albertsen, 2000)
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From page 208... ...
Many have not been persuaded by this evidence, however, because of concerns about lead-time and length biases. Recent attention has focused on evidence that prostate cancer mortality rates began declining in the United States (Tarone et al., 2000)
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From page 209... ...
The principal treatment options for localized prostate cancer include radical prostatectomy, external beam or interstitial radiation therapy, hormonal treatment, cryosurgical ablation, brachytherapy, and no treatment (expectant management or "watchful waiting". New and investigational treatments, such as gene therapy, are not reviewed here.
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From page 210... ...
A retrospective study in Sweden reported a disease-specific mortality rate of 50 to 100 percent for patients with conservatively treated localized tumors, but the denominator included only men who had died of prostate cancer (Aus, 1994~. The same denominator problem affects other studies reporting high mortality rates with conservative treatment (Borre et al., 1997~.
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From page 211... ...
. As with breast cancer, the psychological morbidity that may occur while the patient awaits the possibility of having cancer may be significant, but fewer studies have been performed on .
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From page 212... ...
The 1 potential iatrogenic complications of treatment for prostate cancer are substantial. Chief among these are impotence and incontinence, but several other adverse effects are possible.
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From page 213... ...
An analysis from the Medicare perspective by the Office of Technology Assessment of the U.S. Congress estimated that, given favorable assumptions, a one-time digital rectal examination-PSA screening would cost from $14,200 per year of life saved at age 65 to $51,290 per year of life saved at age 75, although the report emphasized that the estimates were highly sensitive to arguable assumptions (U.S.
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From page 214... ...
Many clinicians fee! compelled to screen patients for prostate cancer to protect them
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From page 215... ...
42-43~. Referring to the controversy surrounding the National Institutes of Health consensus conference statement on breast cancer screening, the absence of a similar phenomenon for prostate cancer screening and the likely role that language has played in the acceptability of the prostate cancer screening policy are worth noting.
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From page 216... ...
Population policy also requires consideration of resources: whether it is appropriate to invest in screening, especially for an intervention of uncertain effectiveness and safety, if it comes at the expense of other services. Policy positions opposing routine screening of the population for prostate cancer have therefore been issued in the United States by the U.S.
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From page 217... ...
For example, the dramatic escalation in PSA screening in the United States in the early 1990s was accompanied by a striking increase in the performance of radical prostatectomies (Lu-Yao and Greenberg, 1994; Wilt et al., 19991. Many of these operations, especially the large number performed on men over age 75, may not have been indicated.
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From page 218... ...
Pap Smear A fundamental difficulty in the evaluation of screening tests for cervical cancer is the lack of reliability of the reference standard: cytological and histological interpretation of cervical specimens. Even among expert pathologists, interobserver variations in interpreting atypical squamous cells of undetermined significance and low-grade squamous intracpithelial lesions are substantial (Storer and Schiffman, 2001~.
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From page 219... ...
The principal harms relate to the consequences of false-positive and false-negative results. As with other screening tests, psychological harms are a potential concern.
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From page 220... ...
For example, in one analysis, annual use of the AutoPap cytology smear was estimated to cost $166,000 per year of life saved, whereas use of AutoPap every 4 years cost $7,777 per year of life saved (Brown and Garber, 1999~. Some have cautioned that the resources expended to pay for these adjunctive technologies could compromise the delivery of cervical cancer screening to high-risk groups (Sawaya and Grimes, 1999~.
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From page 222... ...
. Under such conditions it is reasonable to examine whether resources spent on screening tests of uncertain benefit would save more lives and achieve greater health gains if they were invested in health care services for which effectiveness is more certain.
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From page 223... ...
There is essentially universal agreement across organizations that all adults age 50 and older should be screened for colorectal cancer, that all women should receive mammograms every 1 to 2 years beginning at least by age 50 (some say age 40) , and that all sexually active women with a cervix should be screened regularly for cervical cancer.
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