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Dr. Smith is Director, Cancer Screening, Cancer Control Sciences Department, American Cancer Society, Atlanta, GA.
Dr. Cokkinides is Program Director, Risk Factor Surveillance, Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, GA.
Dr. Eyre is Chief Medical Officer and Executive Vice President for Research and Cancer Control, American Cancer Society, Atlanta, GA, and Editor in Chief of CA.
| ABSTRACT |
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| INTRODUCTION |
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In 2001, the ACS published revisions to the early detection guidelines for colorectal cancer, endometrial cancer, and prostate cancer, and an updated narrative related to testing for early lung cancer detection.2 No guideline updates were announced in the 2002 yearly report,3 but during 2001 to 2002, the ACS convened expert groups to update guidelines for the early detection of cervical cancer, which were published in late 2002,4 and breast cancer, which will be published in 2003. In 2002, the ACS also held a workshop related to emerging technologies for colorectal cancer screening in order to determine if the evidence was sufficient to include these tests among those currently recommended as options for screening.
In addition to providing a summary overview of existing ACS recommendations for early cancer detection, in this issue, we provide: (1) a description of an additional option to the current recommendations for fecal occult blood tests for colorectal cancer screening; (2) an update of recommendations for the cancer-related check-up; (3) a summary of the recent update of the guidelines for cervical cancer screening; (4) a description of recent literature that relates to cancer screening recommendations; and (5) a summary of current screening rates among US adults.
| SCREENING FOR BREAST CANCER |
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In last years annual guidelines review, we described several challenges to existing recommendations to mammography and breast self-examination (BSE).3 In particular, a Cochrane Collaboration Review on screening for breast cancer with mammography concluded that there was no reliable scientific evidence that screening for breast cancer reduces mortality,8,9 and a report from the Canadian Task Force on Preventive Medicine concluded that routine teaching of BSE should be excluded from periodic health examinations in women aged 40 to 69 since there was fair evidence of no benefit, and good evidence of harm.10 In the interim, there have been new developments in each of these areas.
Olsen and Gøtzsches conclusion that there was no evidence to conclude that breast cancer screening reduces breast cancer mortality rested primarily on their critique of the underlying methodology of the breast cancer screening randomized, controlled trials (RCTs). They also concluded that breast cancer mortality as a study endpoint was biased in favor of screening. Further, they argued that screening led to excess harms, including excess mastectomy rates in screen-detected cases, and excess deaths in screen-detected cases resulting from radiotherapy-induced cardiovascular mortality.8
The Cochrane Report has received considerable scrutiny, due largely to the credibility of the Cochrane Collaboration11 and The Lancet, but also in response to considerable press and electronic media coverage. However, the conclusions of independent reviews by several governments, including Sweden12 and the Netherlands,13 expert groups such as the USPSTF,7 the International Agency for Research on Cancer,14 and the European Institute of Oncology,15 and individual researchers16,17 were uniformly that the analysis by Olsen and Gøtzsche was flawed, and that the Cochrane Report had not provided credible evidence to support their claim that there was no reliable scientific evidence that screening for breast cancer reduces mortality. Furthermore, their claim that radiotherapy results in excess cardiovascular deaths was based on older studies and inconsistent with current approaches to designing radiation fields that avoid the heart. Long-term follow up of more recently treated cases shows no such effect.18,19 The claim that breast cancer screening results in excess mastectomies was also misplaced since the detection of smaller tumors creates the opportunity for breast-conserving therapy, and as mammography rates have increased, mastectomy rates have declined.20–22 Drawing on data from the Florence, Italy screening program, Paci, et al. recently showed that mastectomy rates had fallen 40 percent since the establishment of a policy of offering breast cancer screening with mammography.23
Although Olsen and Gøtzsches dismissal of the value of breast cancer screening has been summarily discredited, there is a broad range of opinion about just how much benefit can be derived from breast cancer screening.24 Thus, while the totality of the RCT evidence tells us clearly that breast cancer screening leads to a reduction in breast cancer mortality, relying on the actual measure of benefit from individual trials or meta-analyses is more problematic since the RCTs represent technology and technique over a 40-year period as well as a broad range of protocol elements that influence screening performance and outcomes.25 Further, it is also important to know how much screening benefits individuals who attend screening since estimates of benefit from the RCTs are based on breast cancer mortality differences in groups randomized to an invitation to screening versus usual care, not differences in mortality among screened and non-screened groups. The recent trend toward evaluating the impact of large, population-based screening programs has the potential to provide us with a clearer measurement of the benefit of modern mammography.
Among recent publications, two recent examples of the evaluation of service screening in Europe are noteworthy. In Sweden, Duffy and colleagues evaluated long-term trends in breast cancer mortality based on exposure to screening at both the population and individual level. The most recent report26 expanded an earlier analysis in a smaller geographic area in Sweden27 to seven counties in the Uppsala region, representing more than one-third of the Swedish female population. Duffy, et al. compared breast cancer mortality in the pre-screening and post-screening periods among women aged 40 to 69 in six counties, and 50 to 69 in one county. In all counties together, breast cancer mortality was 44% lower in the post-screening period compared with the pre-screening period among women who actually had attended screening (RR = 0.56, 95% CI = 0.50 - 0.62). When all incident tumors were examined (i.e., cancers detected in women attending screening and in women not attending screening) after adjustment for selection bias, the policy of offering screening to the population was associated with a 39% mortality reduction (RR = 0.61, 95% CI = 0.55 - 0.68).26 Greater breast cancer mortality reductions were observed in those counties that had a policy of offering breast cancer screening for longer than 10 years (-32%) compared with counties that had offered screening less than 10 years (-18%). Since screening programs take several years or more to be established, longer periods of follow-up are necessary in order to measure the impact of screening. Similar mortality reductions have been observed in the Florence, Italy screening program (also comparing breast cancer mortality among attenders and non-attenders to screening) and in the population before and after the introduction of screening.28 Furthermore, after excluding the breast cancer cases diagnosed at the first screening examination (i.e., the prevalent screening round), the incidence rate of Stage II or greater breast cancer cases was 42% lower in screened women compared with the women diagnosed with breast cancer that had not been invited to screening (RR = 0.58, 95% CI: 0.45-0.74). These data demonstrate that modern, organized screening programs with high rates of attendance can achieve breast cancer mortality reductions equal to or greater than those observed in the RCTs.
When the Canadian Task Force concluded that the evidence did not justify teaching BSE, their conclusion was strongly influenced by early results from a randomized trial of BSE instruction in Shanghai, China.29 In 2002, Thomas, et al. published extended follow-up data from the Shanghai Trial of Breast Self-Examination and concluded that intensive instruction in BSE did not result in reduced breast cancer mortality, and was associated with a higher rate of benign breast biopsy.30 The authors concluded that programs consisting of BSE-only would be unlikely to reduce mortality, and that women who chose to do BSE should be informed that its efficacy is unproven, and that the practice could lead to increased risk of benign breast biopsy.
At first glance, these results may seem counterintuitive. However, examination of the results shows a relatively high rate of self-detection of localized breast cancer in the control group, suggesting that a significant proportion of the women in the Shanghai textile industry were highly responsive to new breast symptoms without formal instruction in BSE. Further, the authors have been careful to distinguish that they were measuring the effect of BSE instruction, not BSE per se. Thus, while the prognostic advantage of smaller breast tumor sizes is consistently evident, there may be a limit to the potential of BSE to measurably improve on what is achieved through incidental self-detection in a highly aware population. While there are some data that suggest that highly regular and competent BSE is associated with more favorable tumor characteristics among women with self-detected tumors,31 it may also be the case that the majority of women will not practice BSE in that manner. It is also possible that the contribution of BSE is lessened as a population gains increasing awareness about breast cancer and symptoms of breast cancer, and has increasing access to mammography.
| SCREENING FOR CERVICAL CANCER |
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Previously, the ACS recommended that annual screening for cervical cancer begin at age 18, or the age of onset of sexual intercourse, based on whichever was first. After three consecutive normal tests, screening could then be done less frequently. The new guideline reflects the current understanding of the underlying etiology of cervical intraepithelial neoplasia, and takes into consideration new screening and diagnostic technologies that have emerged since the late 1980s. The ACS now recommends that cervical cancer screening should begin approximately three years after the onset of vaginal intercourse, but no later than 21 years of age. Cervical screening should be performed annually with conventional cervical cytology smears, or every two years using liquid-based cytology, until age 30. Starting at age 30, women who have had three consecutive, technically satisfactory, normal/ negative cytology test results may continue screening every two to three years; women who do not meet these criteria should continue screening as they have before age 30. Women with an intact cervix who are age 70 and older may elect to cease cervical cancer screening if they have had both three or more documented, consecutive, technically satisfactory, normal/ negative cervical cyto-logy tests, and have had no abnormal/positive cytology tests within the 10-year period prior to age 70. Women with a history of cervical cancer, in utero exposure to diethylstilbestrol (DES), and/or who are immunocompromised (including HIV+) should continue cervical cancer screening for as long as they are in reasonably good health and do not have a life-limiting chronic condition. However, with these recommen-dations in mind, women over the age of 70 should discuss their need for cervical cancer screening with a health care professional, and make an informed decision about continuing screening based on the potential benefits, harms, and limitations of screening.
Women who have had a subtotal hysterectomy should continue cervical cancer screening according to the recommendations for average-risk women. Cervical cancer screening is not indicated for women who have had a total hysterectomy (with removal of the cervix) for benign gynecologic disease. Women with a history of CIN2/3, or for whom it is not possible to document the absence of CIN2/3 prior to/or as the indication for the hysterectomy, should be screened until three documented, consecutive, technically satisfactory, normal/negative cervical cytology tests and no abnormal/ positive cytology tests (within a 10-year period) are achieved. Women with a history of in utero DES exposure and/or a history of cervical carcinoma should continue screening after hysterectomy for as long as they are in reasonably good health and do not have a life-limiting chronic condition.
| SCREENING AND SURVEILLANCE FOR THE EARLY DETECTION OF ADENOMATOUS POLYPS AND COLORECTAL CANCER |
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More intensive surveillance is recommended for individuals at increased risk due to a history of adenomatous polyps, a personal history of curative-intent resection of colorectal cancer or a family history of either colorectal cancer or colorectal adenomas diagnosed in a first-degree relative before age 60, or for individuals who are high-risk due to a history of inflammatory bowel disease of significant duration or the presence of one of two hereditary syndromes (Table 2
).
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In April 2002, the ACS Colorectal Cancer Advisory Group organized a workshop to review emerging technologies in colorectal cancer screening, including CT colonography (also known as virtual colonoscopy); immunochemical FOBT, with a focus on the !nSureTM immunochemical test; and stool tests for the detection of altered human DNA in stool. A complete summary of the workshop and the Advisory Groups assessment of these new technologies is published in this issue of the journal (see 44).32 The report also includes statements related to capsule video endoscopy (the camera in a capsule) due to the high public visibility of this test. The Advisory Group concluded that while CT colonography and stool tests for DNA mutations are promising new technologies, there is insufficient evidence at this time to recommend either test for routine screening for colorectal cancer. Likewise, there is insufficient evidence to support the use of capsule video endoscopy. However, the Advisory Group concluded that the evidence showing improved specificity with immunochemical tests, and the lack of requirements to adhere to dietary restrictions prior to the test, was sufficiently persuasive to update the guideline statement for FOBT to include immunochemical tests. Thus, the guideline for FOBT in the ACSs Recommendations for Screening and Surveillance of the Early Detection of Adenomatous Polyps and Colorectal Cancer is appended to include the following statement: "in comparison with guaiac-based tests for the detection of occult blood, immunochemical tests are more patient-friendly, and are likely to be equal or better in sensitivity and specificity." The ACS guidelines for colorectal cancer screening have been updated to reflect the recommended modification (Table 1
).
| SCREENING FOR ENDOMETRIAL CANCER |
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| SCREENING FOR PROSTATE CANCER |
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Men at high risk, including men of African descent (specifically sub-Saharan African descent) and men with a first-degree relative diagnosed at a younger age should begin testing at age 45. Men at even higher risk of prostate cancer due to multiple first-degree relatives diagnosed with prostate cancer at an early age could begin testing at age 40. However, if PSA is less than 1.0 ng/ml, no additional testing is needed until age 45. If PSA is greater than 1.0 ng/ml but less than 2.5 ng/ml, annual testing is recommended. If PSA is 2.5 ng/ml or greater, further evaluation with biopsy should be considered. Men at high risk also should be informed about the benefits and limitations of testing for early prostate cancer detection and treatment so that they can make an informed decision with a clinicians assistance.
Leading organizations current recom-mendations related to testing for early prostate cancer detection reflect the limits of current knowledge of the benefits of testing as well as potential harms associated with treatment. At this time, the accumulation of evidence from observational studies, surveillance data, and natural experiments provides sufficient supporting evidence to endorse informed decision making about prostate cancer screening. Two large randomized trials of prostate cancer screening are also underway, i.e., the European Randomized Study of Screening for Prostate Cancer (ERSPC), which is being conducted in seven European countries, and the US National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Trial (PLCO), which is being conducted in ten locations in the United States.34,35 Investigators in the ERSPC and PLCO trials also have entered into a collaboration to increase statistical power above that which exists with either study alone, carry out subgroup analysis, and work together on the common goal of "sound and efficient evaluation of the screening programs."34 Results from these trials are expected in 2005 to 2008.
In 2002, results were published from a Swedish trial designed to determine whether radical prostatectomy for localized disease was associated with a survival advantage compared with expectant management (i.e., watchful waiting).36 Between 1989 to 1999, Holmberg and colleagues randomized symptomatic men with localized prostate cancer (UICC Stage T1b, T1c, or T2) to receive either radical prostatectomy or watchful waiting. After an average 6.2 years of follow-up, there was a statistically significant difference in the rate of distant metastases (relative hazard 0.63, 95% CI, 0.41 - 0.96), and disease-specific mortality (relative hazard 0.50, 95% CI, 0.27 - 0.91) in the group randomized to radical treatment compared with the group randomized to watchful waiting. In an accompanying editorial, Walsh37 applauded the results and claimed that they were the first concrete evidence to answer the dilemma posed by Whitmore in 1990:38 "Is cure necessary in those in whom it may be possible, and is cure possible in those in whom it is necessary?" However, Walsh also noted that while these results answered a fundamental question about whether or not treatment reduced prostate cancer mortality, men still will be well served by careful consideration of treatment options based on tumor characteristics and expected longevity.
The results from the Swedish study add to the body of evidence supporting the conclusion that treatment of early-stage prostate cancer reduces mortality.39,40 However, the men in the Swedish study all were symptomatic, and many policy makers and groups that issue guidelines will choose to await results from RCTs of asymptomatic men randomized to a group invited to screening versus usual care. One important finding in the Swedish trial is that men in both groups experienced diminished quality of life due either to treatment or (in the case of the watchful waiting group) due to the effects of progressive disease.41 The implications of these findings and other evidence of treatment-related harms indicate that despite growing evidence of the efficacy of screening, men still should participate in a process of assisted informed decision making about testing for early prostate cancer detection.
| TESTING FOR EARLY LUNG CANCER DETECTION |
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In last years guideline update, we described planning for a large RCT of lung cancer screening in the United States. In September 2002, the NCI launched the National Lung Screening Trial, which will enroll 50,000 men and women at high risk for lung cancer, to evaluate the efficacy of lung cancer screening. The trial centers represent the collaboration of two groups, i.e., 10 PLCO centers and 20 American College of Radiology Imaging Network (ACRIN) centers. Men and women are eligible to participate if they are current or former smokers between the ages of 55 and 74, in good general health, with lifetime exposure to cigarette smoking of at least 30-pack years, no chest or lung scan with CT within 18 months, and not participating in any other cancer screening trial (with the exception of melanoma skin cancer). Former smokers must have stopped smoking within the previous 15 years. Individuals must have no prior history of lung cancer, and must not have been treated for any other cancer in the past five years with the exception of non-melanoma skin cancer and most in situ cancers. Individuals who meet eligibility requirements will be randomized to either a group invited to three rounds of spiral CT or a group invited to three rounds of standard chest x-ray. There will be no out-of-pocket costs for the screening tests, and participants who are current smokers can receive referrals to smoking cessation resources if they desire to quit.
The most immediate challenge to any large trial is rapid enrollment, and slow recruitment into a trial delays the completion of the study. The ACS is collaborating with the NCI at the national and local level to assist with recruitment in order to accelerate accrual of study participants. More information about the trial can be found on the NLST Web site at http://www.nci.nih.gov/nlst/.
| THE CANCER-RELATED CHECK-UP |
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Since 1980, the ACS has recommended a cancer-related check-up every three years for individuals aged 20 to 39, and annually for individuals aged 40 and older. In the past, it was likely assumed that routine check-ups would be an opportunity to include case-finding examinations and discussions with patients that were specific to cancer. However, as recommendations for routine check-ups have been replaced by recommendations that apply to specific conditions (including cancer screening) and populations, the periodicity of a general health check-up when these case-finding examinations might take place has become less clear. It also would make very little sense for a cancer-related check-up to take place as a separate visit apart from other preventive health measures such as measuring blood pressure, testing for diabetes, etc., as well as health counseling that is relevant to cancer, and other chronic conditions such as guidance about diet, alcohol consumption, and physical activity. Thus, the ACS now recommends that the cancer-related check-up occur on the occasion of a general, periodic health ex-amination, rather than as a stand-alone exam done at a specific interval based on an individuals age (Table 1
).
| CANCER SCREENING: COLORECTAL, BREAST, AND CERVICAL CANCERS |
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Breast Cancer Screening
In the 2000 BRFSS survey, the proportion of US women aged 40 to 64 reporting having had a mammogram in the last year was 62.5 percent, and among women 65 and older, the proportion reporting a recent mammogram was slightly higher (65.3%). The proportion of women who reported having had both a mammogram and clinical breast exam in the previous year was 56.9 percent among women aged 40 to 64, and 54.3 percent among women aged 65 and older (Table 3
).
Prostate Cancer Screening
The 2001 BRFSS survey was the first occasion where national data on testing for early prostate cancer detection with the prostate-specific antigen (PSA) test and digital rectal examination (DRE) were collected. Among men aged 50 and older, 56.7 percent reported having had a PSA test, and 55.8 percent reported having had a DRE (Table 3
).
Colorectal Cancer Screening
In the 2001 BRFSS survey, less than 40 percent of adults aged 50 and older reported having had a recent screening exam for colorectal cancer. Men were slightly more likely than women to have received an endoscopic exam (flexible sigmoidoscopy or colonoscopy) within the preceding five years (38.7% versus 36.6%). Less than one in four men and women reported having had a recent fecal occult blood test (FOBT) using a home kit (23.6% and 23.0%, respectively) (Table 3
).
Trends in Cancer Screening by Racial and Ethnic Patterns
Because there are disparities in risks for cancer among racial and ethnic groups in the United States, comparison of the utilization of cancer screening tests between major racial and ethnic groups is important. National trend data representative of the US adult civilian population from the NHIS provides the most comprehensive compilation of cancer screening utilization data across three major racial and ethnic groups—Whites (non-Hispanic), Blacks or African Americans (non-Hispanic), and Hispanics.46 According to the US Census Bureau, in 2000, 75.1 percent of the US population was White, and the other two major race/ethnic groups were Black or African American (12.3%) and Hispanic (12.5%). Other racial and ethnic groups are much smaller, e.g., American Indians or Alaska Natives (0.9%), Asians (3.6%) and Native Hawaiians and other Pacific Islanders (0.5%).47
In this section, results on cancer screening trends for cervical, breast, prostate, and colorectal cancer are presented for all race/ethnic groups combined, and separately for Whites, African Americans, and Hispanics. Recent trend data for American Indian/Alaska Native, Asian, Native Hawaiian/Pacific Islander are not available due to insufficient sample size, but comparisons for the period 1988 to 1992 are available from the NCI.48
Between 1987 and 2000, the proportion of women aged 25 and older who had a recent Pap test (within the last three years) increased by 11 percent in all race/ethnic groups combined. The lowest rate of increase occurred among African-American women (4%) and the highest rate of increase occurred in Hispanic women (13%) (Figure 1
- Panel A).
Mammography trend data between 1987 and 2000 show impressive progress in breast cancer screening rates across all race and ethnic groups. In 1987, the proportion of women aged 40 and older reporting a recent mammogram was under 30 percent, but by 2000, the proportion of women having a recent mammogram (within the last two years) increased over 140 percent across all race and ethnic groups (Figure 1
- Panel B).
The improving rates of cervical and breast cancer screening utilization among African-American women (and in particular, those who are medically underserved and uninsured) may be a reflection of the positive impact the CDCs National Breast and Cervical Cancer Early Detection Program (NBCCEDP) has had in increasing access and coverage for breast and cervical cancer screening.49 The NBCCEDP is improving health care for underserved women through outreach, public and professional education, improved access to services, diagnostic evaluation, case management, treatment services, and quality assurance measures. Between July 1991 and September 2001, the program served about 1.5 million underserved women, provided more than 3.5 million screening exams, and diagnosed more than 9,000 breast cancers, 48,170 precancerous cervical lesions, and 831 cervical cancers.50
National trend data pertaining to prostate cancer screening are available for DRE in men aged 50 and older since the late 1980s. During the period of 1987 and 1998, there was a 28% overall increase in DRE use among men (aged 50 and older). In 1998, White men were more likely than African-American and Hispanic men to receive a recent DRE test (52.2% versus 42.6% and 35.8%, respectively) (Figure 1
- Panel C).
Colorectal cancer screening tests consistently have remained underutilized during the period of 1987 through 1998; also, prevalence use of having a recent endoscopy procedure has been consistently lower in women compared with men across all race and ethnic groups (data not shown). During the period of 1987 to 1998, the proportion reporting having had a recent screening exam for colorectal cancer (having a FOBT in the last year or an endoscopy procedure within the last three years) increased in women by 25 percent and in men by 68 percent. Therefore, although colorectal cancer screening rates are still disturbingly low, some modest improvements in the rate of recent screening have been achieved across race and ethnic groups (Figure 1
- Panel D).
Studies have consistently shown that levels of income, education, and presence or absence of health insurance and usual source of health care are all determinants associated with individual use of health services, and are especially strong predictors of the use of preventive services, including cancer screening. These differences in the prevalence utilization of cancer screening among racial and ethnic groups have been associated with various factors, including socioeconomic and cultural factors.51–53 Other relevant correlates include lifestyle behaviors (e.g., lack of physical activity, alcohol intake, and cigarette smoking), aspects of the social environment, (e.g., educational and economic opportunities, neighborhood and work conditions), aspects of the affecting health care environment (e.g., access to health care, physician recommen-dation), and migration trends.54–56 It has been estimated that if health care access were to become more widespread for those race/ethnic groups which comprise most of the underserved population, a 3-to-10% gain in improved use of recent tests for the early detection of cervical and breast cancer, respectively, could be achieved.57 While these improvements may seem modest, the predicted gains in screening usage would represent a substantial public health advance for those race and ethnic groups that currently underutilize screening services.
| Footnotes |
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* The ACS withdrew its recommendation for a baseline examination between the ages of 35 and 40 in 1992. (Dodd GD. American Cancer Society guidelines on screening for breast cancer. An overview. Cancer 1992;69:1885-1887.) ![]()
| REFERENCES |
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