Appendix C
Epidemiology of Colorectal Cancer and Colorectal Cancer Screening: A Background Paper

Bernard Levin, M.D., Ph.D.,

M.D. Anderson Cancer Center, and

Michael Pignone, M.D., M.P.H.,

University of North Carolina at Chapel Hill

BURDEN OF DISEASE

Estimates show that in 2007, there were more than 150,000 new cases of colorectal cancer and over 50,000 deaths from this disease in the United States, making it the second most common cause of death from cancer (ACS, 2007). The estimated lifetime probability at birth of developing colorectal cancer in the United States is approximately 6 percent, and the probability of dying from the disease is about 3 percent (NCI, 2004).

The incidence of colorectal cancer is higher in men than in women, and increases with age for both genders. In the United States, age-adjusted incidence ranges from 48.3 per 100,000 per year in Hispanic men to 72.5 per 100,000 in African American men. In women, it ranges from 32.3 in Hispanics to 56.0 in African Americans per 100,000 per year (NCI, 2004). The age-adjusted mortality rates for all races and genders are 24.8 in men and 17.4 in women per 100,000 per year (NCI, 2004). Mortality is higher for African Americans than for white people (Figures C-1 and C-2, Table C-1).

Worldwide, estimates show that each year nearly 1 million new cases of colorectal cancer occur and nearly 500,000 deaths result from the dis-

The responsibility for the content of this article rests with the authors and does not necessarily represent the views of the Institute of Medicine or its committees and convening boards.



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Appendix C Epidemiology of Colorectal Cancer and Colorectal Cancer Screening: A Background Paper Bernard Levin, M.D., Ph.D., M.D. Anderson Cancer Center, and Michael Pignone, M.D., M.P.H., Uniersity of North Carolina at Chapel Hill BURDEN OF DISEASE Estimates show that in 2007, there were more than 150,000 new cases of colorectal cancer and over 50,000 deaths from this disease in the United States, making it the second most common cause of death from cancer (ACS, 2007). The estimated lifetime probability at birth of developing colorectal cancer in the United States is approximately 6 percent, and the probability of dying from the disease is about 3 percent (NCI, 2004). The incidence of colorectal cancer is higher in men than in women, and increases with age for both genders. In the United States, age-adjusted incidence ranges from 48.3 per 100,000 per year in Hispanic men to 72.5 per 100,000 in African American men. In women, it ranges from 32.3 in Hispanics to 56.0 in African Americans per 100,000 per year (NCI, 2004). The age-adjusted mortality rates for all races and genders are 24.8 in men and 17.4 in women per 100,000 per year (NCI, 2004). Mortality is higher for African Americans than for white people (Figures C-1 and C-2, Table C-1). Worldwide, estimates show that each year nearly 1 million new cases of colorectal cancer occur and nearly 500,000 deaths result from the dis- The responsibility for the content of this article rests with the authors and does not neces- sarily represent the views of the Institute of Medicine or its committees and convening boards. 0

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0 IMPROVING COLORECTAL CANCER SCREENING 600 Black male White male 500 Black female White female 400 Rate per 100,000 300 200 100 0 30–34 35–39 40–44 45–49 50–54 55–59 60–64 65–69 70–74 75–79 80–84 85+ Age Group FIGURE C-1 SEER incidence and mortality rates by gender, 1995–1999. SOURCE: NCI (2004). ease (NCI, 2004). The highest incidence rates occur in North America, Western Europe, and Australia; the lowest incidence rates are found in nonwhite populations of sub-Saharan Africa and India (Figure C-3; Ferlay et al., 2001). However, rates in Asia are increasing in countries adopting Western lifestyle habits (Vainio and Miller, 2003). Colorectal cancer incidence and mortality are declining in developed countries. In the United States, between 1973 and 1995, mortality declined by 20 percent and incidence declined by 7 percent. Both continued to decline from 1995 to 2003 (NCI, 2006). Colorectal cancer survival and mortality differ according to stage at diagnosis. Survival rates at 5 years are more than 80 percent for patients diagnosed with local disease, and over 60 percent for regional disease. Despite recent advances in chemo- therapy, 5-year survival with metastatic colorectal cancer is less than 10 percent. Currently, Surveillance Epidemiology and End Results (SEER) data show that only about 40 percent of colorectal cancers are localized at ure C1.diagnosis; about 37 percent have regionally spread, and 19 percent have metastasized to distant sites.

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0 APPENDIX C 35 30 Deaths per 100,000 Resident Population 25 20 All races (incl Hisp), all ages, both sexes 15 White (incl Hisp), all ages, both sexes Black (incl Hisp), all ages, both sexes 10 Hispanic (any race), all ages, both sexes AI/AN (incl Hisp), all ages, both sexes 5 API (incl Hisp), all ages, both sexes 0 1980 1985 1990 1995 2000 2004 Year FIGURE C-2 Colon and rectal cancer mortality for both sexes and all ages, by race and ethnicity from 1980–2004. NOTE: Death rates calculated by the National Can- cer Institute using SEER*Stat. Death rates are age-adjusted to the 2000 U.S. stan- dard population (19 age groups: <1, 1–4, 5–9, ... , 80–84, 85+). Population counts for denominators are based on Census populations as modified by NCI. Regres- sion lines were calculated using the Joinpoint Regression Program. Due to data availability issues, the time period used in the calculation of the joinpoint regres- sion model may differ for selected racial groups or counties. The regression lines represent annual percent change (APC) over specified time intervals. Rates used in the calculation of the APC are age-adjusted to the 2000 U.S. standard population (19 age groups: <1, 1–4, 5–9, ... , 80–84, 85+). Statistics for minorities may be af- fected by inconsistent race identification between the cancer case reports (sources Figure C2, R01298. for numerator of rate) and data from the Census Bureau (source for denominator of rate); and from undercounts of some population groups in the census. Hispanic mortality data for the United States has been excluded for the following states: Connecticut, Louisiana, Maine, Maryland, Mississippi, New Hampshire, New York, North Dakota, Oklahoma, Vermont, and Virginia. The data on Hispanic and non-Hispanic mortality for these states may be unreliable for the time period used in the generation of the trend (1990–2001) and has been excluded from the calculation of the United States recent trend. This was based on the value of the Hispanic Index. AI/AN = American Indian and Alaska Native, APC = annual percentage change, API = Asian and Pacific Islander, Hisp = Hispanic. SOURCE: Data and notes provided to the State Cancer Profiles website by the National Vital Statistics System public use data file (NCI, 2008). See http://statecancerprofiles .cancer.gov/ and http://statecancerprofiles.cancer.gov/historicaltrend/joinpoint .noimage.html.

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0 IMPROVING COLORECTAL CANCER SCREENING TABLE C-1 U.S. Colorectal Cancer Incidence and Mortality Data 2000–2003, based on SEER incidence data and National Center for Health Statistics (NCHS) mortality data Men Women Incidence rate Mortality rate Incidence rate Mortality rate (per 100,000) (per 100,000) (per 100,000) (per 100,000) 61.7 24.0 45.3 16.8 All races White 61.4 23.4 44.7 16.2 Black 72.9 33.4 56.1 23.4 Asian/Pacific 51.2 15.4 35.7 10.5 Islander American Indian/ 52.7 15.6 41.9 11.0 Alaskan Native Hispanic 47.3 17.3 32.7 11.3 SOURCE: NCI (2006). NATURAL HISTORY The natural history of colorectal neoplasia has been well studied at the molecular as well as at the epidemiologic level. Colorectal adenomas, the precursors of nearly all sporadic colorectal cancers, are found in up to 40 percent of persons by 60 years of age. Experimental, epidemiologic, and genetic studies suggest that colorectal adenomas and cancers result from complex interactions between inherited susceptibility and environ- mental or lifestyle factors (Young et al., 2002). The adenoma–carcinoma sequence consists of the progression from normal-appearing mucosa to small tubular adenoma to larger adenomas and those with more advanced histological features (villous changes, high-grade dysplasia, or both) and then development of cancer. More than 90 percent of adenomatous pol- yps do not progress to cancer. Some evidence suggests that measures that reduce the incidence and prevalence of colorectal adenomas, such as polypectomy, may result in a subsequent decrease in the risk of colorectal cancer (Winawer et al., 1993). RISK FACTORS Individuals with hereditary conditions such as familial adenoma- tous polyposis and hereditary nonpolyposis colorectal cancer have a sig- nificantly increased risk of colorectal cancer, but combined, these two conditions do not account for more than 5 to 6 percent of all cases of colorectal cancer. More common conditions associated with an increased risk include a personal history of colorectal cancer or adenomas; a first degree family history of colorectal cancer or adenomas; a personal history

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0 APPENDIX C FIGURE C-3 International colorectal cancer incidence rates by gender. World- wide, there are 945,000 cases of colorectal cancer per year and 492,000 deaths. In the United States, there are 153,760 cases per year and 52,180 deaths. SOURCE: Parkin et al. (2005). of ovarian or endometrial cancer; and a personal history of long-standing chronic ulcerative colitis or Crohn’s disease (Levin et al., 2002). However, estimates indicate that approximately 70 percent of colorectal cancers arise sporadically. Therefore, early detection and treatment strategies can- not be directed solely to high-risk patients if the goal is to substantially reduce associated morbidity and mortality. A number of other risk factors for colorectal cancer have been identi- fied. Epidemiologic studies have reported that physical inactivity and obesity are associated with an increased risk (Wolin et al., 2007). A high

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0 IMPROVING COLORECTAL CANCER SCREENING consumption of red and processed meat and alcohol and low consumption of vegetables and fruit are also associated with increased risk, although not all studies are consistent (Koushik et al., 2007). SCREENING Randomized trials have found that screening for colorectal cancer with fecal occult blood testing could reduce the incidence and mortality from colorectal cancer (Mandel et al., 1993, 2000). These findings have been extrapolated to other colorectal cancer screening techniques, includ- ing newer occult blood tests, sigmoidoscopy, colonoscopy, and radiologi- cal imaging, that have been shown to be accurate for detecting neoplasia, have relatively low rates of adverse effects, and have reasonable costs (Pignone et al., 2002). Screening Use Despite the proven effectiveness of screening and the availability of several different tests, overall rates of screening remain low in the United States and other developed countries. Recent data from a national tele- phone survey conducted by the CDC’s Behavioral Risk Factor Surveil- lance Study (BRFSS) found that only about half (57 percent) of age-eligible adults reported being up to date with screening (CDC, 2006). Screening has become steadily more common over the past 10 years (see Figures C-4 and C-5), with colonoscopy accounting for much of that increase (Meissner et al., 2006). The use of colonoscopy itself has increased five- fold since before 1998, with most of the increase attributable to colorectal cancer screening or surveillance (Gross et al., 2006). Factors Associated with Colorectal Cancer Screening Many studies have examined factors associated with screening test completion. Subramanian and colleagues reviewed this literature through 2002 and identified 30 articles that addressed factors affecting screening test completion in average-risk adults, 14 of which used multivariate analysis to identify independent effects (Subramanian et al., 2004). They found that age over 65 and less than 85, level of education, and health maintenance organization membership were all associated with comple- tion of a fecal occult blood test (FOBT) or endoscopy. Insurance coverage itself did not have a consistent relationship with screening. Other demo- graphic characteristics, including sex, race, income, and marital status, also were not clearly or consistently associated with screening. Attitudinal variables associated with screening included the belief that cancer is pre-

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07 APPENDIX C 70 60 Percentage Screened 50 40 30 20 10 0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 Year FIGURE C-4 Self-reported colorectal cancer screening levels from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance Sys- tem. The graph shows the rates at which individuals report being up to date with colorectal cancer screening by any method. SOURCE: http://www.cdc .gov/brfss/index.htm. Figure C4, R01298. ventable or curable; commitment to screening; and lack of significant fear or pessimism/fatalism about cancer. More recently, Meissner and colleagues examined patient factors asso- ciated with screening using data from the 2003 National Health Interview Survey (Meissner et al., 2006). They reported bivariate analyses, stratified by sex. Their findings were similar to those of Subramanian and col- leagues (2004), except that having health insurance was strongly associ- ated with screening. Compared with older data from before 2000, recent screening was performed predominantly with colonoscopy (Phillips et al., 2007). It is possible that the use of colonoscopy screening is more closely tied to having health insurance. Subramanian and colleagues (2004) found that several health care provider or system-related factors—including physician recommendation for screening, more physician visits, having a usual source of care, and having preventive visits—were also positively associated with screen- ing. Other analyses have found that most patients who have not been screened report never receiving a recommendation to do so (Klabunde et al., 2005). Few studies have examined practice-level factors, but limited evidence suggests that use of reminder systems, and possibly use of mul- tidisciplinary teams, are associated with more frequent colorectal cancer screening (Hudson et al., 2007).

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0 IMPROVING COLORECTAL CANCER SCREENING Women (age 50+) 50 40 Percentage 30 20 10 0 1987 1989 1991 1993 1995 1997 1999 2001 2003 Year Men (age 50+) 50 40 Percentage 30 20 10 0 1987 1989 1991 1993 1995 1997 1999 2001 2003 Year Any recommended test CRE in past 3 years Colonoscopy in past 10 years Sigmoidoscopy in past 5 years Figure C5 stacked version, R01298.

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09 APPENDIX C FIGURE C-5 Self-reported colorectal cancer screening levels from the National Health Interview Survey 1987–2003. NOTE: Percentages are standardized to the 2000 projected U.S. population by 5-year age groups. The relevant survey ques- tions were redesigned after 1998; broken lines represent these changes. Before 1998, recommended tests included home or office FOBT, colonoscopy, proctoscopy, and sigmoidoscopy, because it was not possible to adequately distinguish between tests during these years. After 1998 the recommended tests include home FOBT, sigmoidoscopy, and colonoscopy. NOTE: CRE = colorectal endoscopy. SOURCE: Figure and note reprinted, with permission, from “Patterns of colorectal cancer screening uptake among men and women in the United States,” 2006. Copyright American Association for Cancer Research (Meissner et al., 2006). REFERENCES ACS (American Cancer Society). 2007. Cancer facts & figures. Atlanta, GA: ACS. CDC (Centers for Disease Control and Prevention). 2006. Increased use of colorectal cancer tests—United States, 2002 and 2004. Morbidity and Mortality Weekly Report 55(11):308– 311. Ferlay, J., F. Bray, P. Pisani, and D. M. Parkin. 2001. GLOBOCAN 000: Cancer incidence, mortality and prealence worldwide, Version .0, IARC CancerBase, No. . Lyon, France: IARCPress. Gross, C. P., M. S. Andersen, H. M. Krumholz, G. J. McAvay, D. Proctor, and M. E. Tinetti. 2006. Relation between Medicare screening reimbursement and stage at diagno- sis for older patients with colon cancer. Journal of the American Medical Association 296(23):2815–2822. Hudson, S. V., P. Ohman-Strickland, R. Cunningham, J. M. Ferrante, K. Hahn, and B. F. Crabtree. 2007. The effects of teamwork and system support on colorectal cancer screening in primary care practices. Cancer Detection and Preention 31(5):417–423. Klabunde, C. N., S. W. Vernon, M. R. Nadel, N. Breen, L. C. Seeff, and M. L. Brown. 2005. Barriers to colorectal cancer screening: A comparison of reports from primary care physicians and average-risk adults. Medical Care 43(9):939–944. Koushik, A., D. J. Hunter, D. Spiegelman, W. L. Beeson, P. A. v. d. Brandt, J. E. Buring, E. E. Calle, E. Cho, G. E. Fraser, J. L. Freundenheim, C. S. Fuchs, E. L. Giovannucci, R. A. Goldbohm, L. Harnack, J. D. R. Jacobs, I. Kato, V. Krogh, S. C. Larsson, M. F. Leitzmann, J. R. Marshall, M. L. McCullough, A. B. Miller, P. Pietinen, T. E. Rohan, A. Schatzkin, S. Sieri, M. J. Virtanen, A. Wolk, A. Zeleniuch-Jacquotte, S. M. Zhang, and S. A. Smith- Warner. 2007. Fruits, vegetables, and colon cancer risk in a pooled analysis of 14 cohort studies. Journal of the National Cancer Institute 99(19):1471–1483. Levin, B., P. Rozen, and G. P. Young. 2002. How should we follow up colorectal premalignant conditions? In Colorectal cancer in clinical practice: Preention, early detection and manage- ment, edited by P. Rozen, G. Young, B. Levin, and S. Spann. London, England: Martin Dunitz, Ltd. Pp. 67–76.

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