Colorectal Cancer Statistics, 2017

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1 Colorectal Cancer Statistics, 2017 Rebecca L. Siegel, MPH 1 ; Kimberly D. Miller, MPH 2 ; Stacey A. Fedewa, PhD 3 ; Dennis J. Ahnen, MD 4 ; Reinier G. S. Meester, PhD 5 ; Afsaneh Barzi, MD, PhD 6 ; Ahmedin Jemal, DVM, PhD 7 1 Strategic Director, Surveillance Information Services, Surveillance and Health Services Research, American Cancer Society, Atlanta, GA; 2 Epidemiologist, Surveillance and Health Services Research, American Cancer Society, Atlanta, GA; 3 Director, Screening and Risk Factor Surveillance, Surveillance and Health Services Research, American Cancer Society, Atlanta, GA; 4 Professor, Division of Gastroenterology, School of Medicine, University of Colorado, Aurora, CO; 5 Epidemiologist, Department of Public Health, Erasmus University, Rotterdam, the Netherlands; 6 Assistant Professor of Clinical Medicine, Department of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA; 7 Vice President, Surveillance and Health Services Research, American Cancer Society, Atlanta, GA Corresponding author: Rebecca L. Siegel, MPH, Surveillance Research, American Cancer Society, 250 Williams Street NW, Atlanta, GA 30303; rebecca.siegel@cancer.org DISCLOSURES: Dennis J. Ahnen serves on the Speakers Bureau for Ambry Genetics and is a Scientific Advisory Board member of EXACT Sciences and Cancer Prevention Pharmaceuticals, all outside the submitted work. Reinier G.S. Meester reports grants from the US National Cancer Institute during the conduct of this study. All other authors report no conflicts of interest. doi: /caac Available online at cacancerjournal.com Abstract: Colorectal cancer (CRC) is one of the most common malignancies in the United States. Every 3 years, the American Cancer Society provides an update of CRC incidence, survival, and mortality rates and trends. Incidence data through 2013 were provided by the Surveillance, Epidemiology, and End Results program, the National Program of Cancer Registries, and the North American Association of Central Cancer Registries. Mortality data through 2014 were provided by the National Center for Health Statistics. CRC incidence rates are highest in Alaska Natives and blacks and lowest in Asian/Pacific Islanders, and they are 30% to 40% higher in men than in women. Recent temporal patterns are generally similar by race and sex, but differ by age. Between 2000 and 2013, incidence rates in adults aged 50 years declined by 32%, with the drop largest for distal tumors in people aged 65 years (incidence rate ratio [IRR], 0.50; 95% confidence interval [95% CI], ) and smallest for rectal tumors in ages 50 to 64 years (male IRR, 0.91; 95% CI, ; female IRR, 1.00; 95% CI, ). Overall CRC incidence in individuals ages 50 years declined from 2009 to 2013 in every state except Arkansas, with the decrease exceeding 5% annually in 7 states; however, rectal tumor incidence in those ages 50 to 64 years was stable in most states. Among adults aged <50 years, CRC incidence rates increased by 22% from 2000 to 2013, driven solely by tumors in the distal colon (IRR, 1.24; 95% CI, ) and rectum (IRR, 1.22; 95% CI, ). Similar to incidence patterns, CRC death rates decreased by 34% among individuals aged 50 years during 2000 through 2014, but increased by 13% in those aged <50 years. Progress against CRC can be accelerated by increasing initiation of screening at age 50 years (average risk) or earlier (eg, family history of CRC/ advanced adenomas) and eliminating disparities in high-quality treatment. In addition, research is needed to elucidate causes for increasing CRC in young adults. CA Cancer J Clin 2017;67: VC 2017 American Cancer Society. Keywords: colon and rectum neoplasms, epidemiology, health disparities, screening and early detection Introduction Colorectal cancer (CRC) is the third most commonly diagnosed cancer among both men and women in the United States. Incidence and mortality rates have been declining for several decades because of historical changes in risk factors (eg, decreased smoking and red meat consumption and increased use of aspirin), the introduction and dissemination of screening tests, and improvements in treatment (mortality). 1,2 In this article, we provide a comprehensive overview of current CRC statistics in the United States, including the estimated numbers of new cases and deaths among men and women in 2017 by age; incidence rates and trends by age, race/ethnicity, and anatomic subsite through 2013; survival for cases diagnosed from 1975 to 2012; and mortality rates and trends through CRC screening prevalence for adults aged 50 years and older are also presented nationally for 2015 and by state for Materials and Methods Data Sources US mortality data from 1930 to 2014 were obtained from the Centers for Disease Control and Prevention s (CDC s) National Center for Health Statistics (NCHS). 3,4 Population-based cancer incidence data in the United States are collected by the VOLUME 67 _ NUMBER 3 _ MAY/JUNE

2 Colorectal Cancer Statistics, 2017 FIGURE 1. Colorectal Cancer Incidence ( ) and Mortality ( ) Rates by Race/Ethnicity and Sex, United States. AI/AN indicates American Indian/Alaska Native; API, Asian American/Pacific Islander; NHB, non-hispanic black; NHW, non-hispanic white. Rates are age adjusted to the 2000 US standard population. *Rates for AI/ANs are based on Contract Health Service Delivery Area (CHSDA) counties; incidence rates exclude data from Kansas. Sources: Incidence: NAACCR, Alaska Natives only: SEER program, Mortality: NCHS, CDC, National Cancer Institute s (NCI s) Surveillance, Epidemiology, and End Results (SEER) program and the CDC s National Program of Cancer Registries. Long-term incidence and relative survival trends dating back to 1975 were based on data from the 9 oldest SEER registries (Connecticut, Iowa, Hawaii, New Mexico, Utah, and the metropolitan areas of Atlanta, Detroit, San Francisco-Oakland, and Seattle- Puget Sound), representing approximately 9% of the US population. 5 The entire SEER catchment area (SEER 9 plus registries for Alaska Natives, Georgia, California, Kentucky, Louisiana, and New Jersey) achieves 28% population coverage and was the source for cancer stage distribution, 5-year relative survival by stage, 5-year cause-specific survival by race/ ethnicity, and incidence trends from 2000 through Incidence and mortality rates for Alaska Natives separate from American Indians were based on cases collected by the TABLE 1. Estimated Numbers of New Colorectal Cancer Cases and Deaths by Age, United States, 2017* NEW CASES DEATHS MALE FEMALE MALE FEMALE AGE, YEARS Count % Count % Count % Count % Birth to 49 7, , , , , , , , , , , , , , , , All ages 71, , , , *Estimates are rounded to the nearest CA: A Cancer Journal for Clinicians

3 TABLE 2. Colorectal Cancer Incidence ( ) and Mortality ( ) Rates by Race/Ethnicity and State, United States INCIDENCE MORTALITY MALE FEMALE MALE FEMALE NHW NHB HISPANIC NHW NHB HISPANIC NHW NHB HISPANIC NHW NHB HISPANIC Alabama * * Alaska 41.2 * * 33.5 * * 14.2 * * 11.5 * * Arizona Arkansas * * California Colorado Connecticut Delaware * * * Dist. Of Columbia * * * Florida Georgia Hawaii 42.7 * * * * * Idaho 41.8 * * * * 11.2 * * Illinois Indiana * Iowa * * Kansas Kentucky * * * Louisiana * * Maine 44.9 * * 35.6 * * 16.6 * * 11.8 * * Maryland Massachusetts Michigan Minnesota * * Mississippi * * * * Missouri * * Montana 44.5 * * 32.9 * * 15.5 * * 10.9 * * Nebraska * * Nevada, New Hampshire 41.4 * * 34.6 * * 14.3 * * 13.6 * * New Jersey New Mexico, 36.3 * * * * 12.1 New York North Carolina North Dakota 54.4 * * 39.6 * * 18.3 * * 12.9 * * Ohio Oklahoma Oregon Pennsylvania Rhode Island * * 13.6 * * South Carolina * * South Dakota 50.2 * * 39.4 * * 19.4 * * 12.5 * * Tennessee * * Texas Utah * * * 9.5 Vermont 41.4 * * 33.6 * * 15.8 * * 12.7 * * Virginia Washington West Virginia * * * * Wisconsin * Wyoming 44.0 * * * 17.0 * * 10.5 * * United States NHB indicates non-hispanic black; NHW, non-hispanic white. Rates are per 100,000 and age adjusted to the 2000 US standard population. *Statistics are not displayed because there were fewer than 25 cases or deaths. This state s incidence data are not included in US combined rates, because they did not meet NAACCR s high-quality standards for 1 or more years during 2009 through Incidence rates are based on data for 2009 through Incidence rates are based on data for 2009 through Sources: Incidence: NAACCR, Mortality: NCHS, CDC, VOLUME 67 _ NUMBER 3 _ MAY/JUNE

4 Colorectal Cancer Statistics, 2017 TABLE 3. Colorectal Cancer Incidence Rates and Proportions of Cases by Tumor Subsite, United States, 2009 to 2013 ALL PERSONS MALE FEMALE RATE % RATE % RATE % Proximal colon Distal colon Rectum Other Total colorectum Rates are per 100,000 and are age adjusted to the 2000 US standard population. Source: NAACCR, SEER program s Alaska Native Tumor Registry and deaths occurring in American Indians/Alaska Natives (AI/AN) in Contract Health Service Delivery Area counties in Alaska, as reported by the NCHS. Because of data limitations, there may be some cross-contamination between rates for Alaska Natives and American Indians provided separately (Fig. 1), particularly for mortality. Some of the data presented herein were previously published in the NCI s SEER Cancer Statistics Review, Combined SEER and National Program of Cancer Registries data, as provided by the North American Association of Central Cancer Registries (NAACCR), were the source for the projection of new CRC diagnoses in 2017, age and subsite distributions, 5-year ( ) average annual incidence rates by race/ethnicity and state, and trends by state from 2004 through CRC screening prevalence data at the state level were obtained from 2014 Behavioral Risk Factor Surveillance System (BRFSS) public use data. 9 The BRFSS is a survey coordinated by the CDC and conducted by individual state health departments that is designed to provide state prevalence estimates of health behaviors. Data are collected from computer-assisted telephone interviews with adults aged 18 years and older. In 2011, the CDC modified the BRFSS weighting procedures and expanded reach to include households without landline telephone service (ie, cellular service only). 10 Therefore, BRFSS estimates for 2011 and later should not be compared with earlier estimates. FIGURE 2. Distribution of Colorectal Tumor Location by Age, United States, Source: NAACCR, CA: A Cancer Journal for Clinicians

5 TABLE 4. Stage Distribution and 5-Year Relative Survival Rates by Race for Colon and Rectal Cancer, United States, 2006 to 2012* ALL RACES COMBINED WHITE BLACK STAGE DISTRIBUTION, % SURVIVAL, % STAGE DISTRIBUTION, % SURVIVAL, % STAGE DISTRIBUTION, % SURVIVAL, % Colon Localized Regional Distant Unstaged All stages Rectum Localized Regional Distant Unstaged All stages *Cases were diagnosed from 2006 to 2012, and all were followed through Source: Howlader N, et al. 7 FIGURE 3. Colorectal Cancer Stage Distribution and 5-Year Cause-Specific Survival* by Race/Ethnicity, United States, AI/AN indicates American Indian/Alaska Native; API, Asian American/Pacific Islander; NHB, non-hispanic black; NHW, non-hispanic white. *Cause-specific survival rates are the probability of not dying from colorectal cancer within 5 years of diagnosis. Patients were followed through Data are based on cases diagnosed in CHSDA counties. Rates for AI/ANs are based on small case numbers, particularly for distant stage disease. Source: SEER program, VOLUME 67 _ NUMBER 3 _ MAY/JUNE

6 Colorectal Cancer Statistics, 2017 coverage, and updated risk factor surveillance. The methods for projecting the total number of new CRC cases and deaths that will occur in 2017 is described in detail elsewhere. 13,14 The proportions of cases and deaths by age were calculated by applying the age distributions for NAACCR incidence data and NCHS mortality data during the most recent data year to the overall estimates. FIGURE 4. Trends in Colorectal Cancer Incidence ( ) and Mortality ( ) Rates by Sex, United States. Rates are age adjusted to the 2000 US standard population and incidence rates are adjusted for reporting delays. Due to improvements in International Classification of Diseases (ICD) coding over time, numerator data for colorectal cancer mortality differ slightly from those presented elsewhere. Sources: Incidence: SEER program, Mortality: US Mortality Volumes 1930 to 1959, US Mortality Data , NCHS, CDC, National CRC screening prevalence was obtained from the NCHS 2015 National Health Interview Survey (NHIS). 11 The NHIS is a centralized survey conducted by the US Census Bureau that is designed to provide national prevalence estimates on health characteristics, such as cancer screening behaviors. Data are collected through computerassisted, in-person interviews of adults aged 18 years and older. The number of additional people screened from 2013 to 2015 was calculated using NHIS and US Census data based on a methodology described elsewhere. 12 The MISCAN-colon model, which is a part of the Cancer Intervention and Surveillance Modeling Network sponsored by the National Cancer Institute (cisnet.cancer.gov/), was used to predict the number of cases and deaths averted under scenarios of different screening rates. Projected New Cases and Deaths in 2017 The most recent year for which incidence and mortality data are available lags 2 to 4 years behind the current year because of the time required for data collection, compilation, quality control, and dissemination. Therefore, the American Cancer Society projects the numbers of new cancer cases and deaths in the United States for the current year to provide an estimate of the contemporary cancer burden. These estimates cannot be used for tracking cancer occurrence over time because they are model-based and because the methodology changes every few years to take advantage of improvements in modeling techniques, increased cancer registration Statistical Analysis CRC cases were classified according to the International Classification of Diseases for Oncology as colon (codes C18.0-C18.9 and C26.0) or rectum (codes C19.9 and C20.9). 15 Colon tumors were further designated by location as proximal (codes C18.0 and C18.2-C18.5), distal (codes C18.6-C18.7), or other (codes C18.1, C18.8, C18.9, and C26.0). Because of the large number of rectal cancer deaths that are misclassified as colon, 16 colon and rectal cancer deaths were combined in all analyses. This misclassification does not affect the calculation of relative survival rates presented herein. All incidence and death rates were age-standardized to the 2000 US standard population and expressed per 100,000 persons, as calculated by the NCI s SEER*Stat software (version 8.3.2). 17 SEER incidence trends were based on rates adjusted for delays in reporting based on SEER delay factors, except for AI/AN rates, which were based on NAACCR combined registries delay factors (Eric J. Feuer, personal communication, 2017). Delay adjustment accounts for the additional time required for the complete registration of cases and more accurately reflects cancer trends in the most recent time period. 18 The lifetime probability of developing cancer was calculated using the NCI s DevCan software (version 6.7.4). 19 Selected Findings Estimated Cases and Deaths in 2017 In the United States in 2017, there are projected to be 135,430 individuals newly diagnosed with CRC and 50,260 deaths from the disease. 20 Although the majority of new cases (58%) occur in people aged 65 years or older, 45% of men and 39% of women are younger than age 65 years at diagnosis (Table 1). Among women, 27% of cases and 40% of deaths occur in those aged 80 years and older, compared with 18% and 27%, respectively, among men (Table 1). Contemporary Incidence and Mortality Overall In the United States, the annual age-standardized incidence rate for CRC during 2009 through 2013, the most recent years for which data are available, was 40.7 per 100,000 persons, and the mortality rate ( ) was 182 CA: A Cancer Journal for Clinicians

7 FIGURE 5. Colorectal Cancer Incidence and Mortality Trends by Age and Sex, United States, Please note: Axis scales are not uniform in order to highlight trends. Rates are age adjusted to the 2000 standard population and incidence rates are adjusted for reporting delays. Sources: Incidence: SEER program, Mortality: NCHS, CDC, per 100,000 persons. Incidence and mortality rates are 30% and 40% higher in men than in women, respectively, 20 although the lifetime risk of disease is similar (4.6% vs 4.2%) because women have longer life expectancy. In addition, the sex disparity differs by age. For example, incidence is not significantly different in men and women younger than age 40 years but is almost 50% higher in men than in women ages 55 to 74 years (131.5 vs 90.7 per 100,000). Reasons for higher rates in men are not completely understood but to some extent likely reflect differences in exposures to risk factors and sex hormones, as well as complex interactions between these influences. 21,22 Racial/ethnic disparities CRC incidence and mortality rates vary substantially by race and ethnicity. Among the 5 major racial/ethnic groups depicted in Figure 1, rates are highest in non-hispanic blacks (NHBs) and lowest in Asian Americans/Pacific Islanders (APIs) (Fig. 1). During 2009 through 2013, incidence rates in NHBs (49.2 per 100,000) were about 20% higher than those in non-hispanic whites (NHWs) (40.2 per 100,000) and 50% higher than those in APIs (32.2 per 100,000). Notably, the magnitude of the disparity for mortality is double that for incidence. During 2010 through 2014, CRC death rates in NHBs (20.5 per 100,000) were 40% higher than those in NHWs (14.6 per 100,000) and twice those in APIs (10.3 per 100,000). It is believed that the higher rates in NHBs are largely driven by disproportionately low socioeconomic status, which is associated with a higher risk of CRC incidence and death. 23,24 According to the US Census Bureau, the poverty rate in 2015 was 24% in blacks compared with 9% in NHWs and 11% in Asians. 25 Approximately 40% of the socioeconomic disparity in CRC VOLUME 67 _ NUMBER 3 _ MAY/JUNE

8 Colorectal Cancer Statistics, 2017 TABLE 5. Trends in Colorectal Cancer Incidence Rates by Age and Subsite, United States, 2000 to 2013 TREND 1 TREND 2 TREND 3 YEARS APC YEARS APC YEARS APC AAPC AAPC Proximal colon Birth to 49 years years * -2.0* -2.0* 65 years * * -4.4* -3.5* Distal colon Birth to 49 years * 1.7* 1.7* years * -2.2* -2.2* 65 years * -5.5* -5.5* Rectum Birth to 49 years * * years * -0.5* -0.5* 65 years * -3.7* -3.7* Appendix/unspecified subsite Birth to 49 years * * 11.8* 6.1* years * 0.8* 0.8* 65 years * -1.9* -1.9* Total colorectum Birth to 49 years * 1.6* 1.6* years * -1.4* -1.4* 65 years * * -4.6* -4.0* AAPC indicates average annual percent change over the most recent 5 data years; APC,: annual percent change based on incidence rates age adjusted to the 2000 US standard population. *The APC or AAPC is significantly different from zero (p <.05). Source: SEER program, Note: Trends are based on incidence rates adjusted for delays in case reporting and were analyzed using the Joinpoint Regression Program, version , allowing up to 2 joinpoints. TABLE 6. Trends in Colorectal Cancer Incidence Rates by Age and Stage, United States, 2000 to 2013 TREND 1 TREND 2 TREND 3 YEARS APC YEARS APC YEARS APC AAPC AAPC Localized Birth to 49 years * 1.3* 1.3* years * -2.8* -1.8* 65 years * * * -3.9* Regional Birth to 49 years * 1.1* 1.1* years * -2.1* -2.1* 65 years * -4.1* -4.1* Distant Birth to 49 years * 3.0* 3.0* years * -0.5* -0.5* 65 years * -2.9* -2.9* Unknown stage Birth to 49 years years * years * * -3.8* -3.8* AAPC indicates average annual percent change over the most recent 5 data years; APC, annual percent change based on incidence rates age adjusted to the 2000 US standard population. *The APC or AAPC is significantly different from zero (p < 0.05). Source: SEER program, Trends are based on incidence rates adjusted for delays in case reporting and were analyzed using the Joinpoint Regression Program, version , allowing up to 2 joinpoints. 184 CA: A Cancer Journal for Clinicians

9 TABLE 7. Trends in Colorectal Cancer Incidence Rates by Age and Race/Ethnicity, United States, 2000 to 2013 TREND1 TREND 2 YEARS APC YEARS APC AAPC AAPC Non-Hispanic white All ages * -2.7* -2.7* Birth to 49 years * 2.3* 2.3* years * * 65 years * * -4.7* -4.1* Non-Hispanic black All ages * * -3.0* -2.4* Birth to 49 years * 1.0* 1.0* years * -2.2* -1.6* 65 years * * -3.9* -3.4* Asian/Pacific Islander All ages * -2.1* -2.1* Birth to 49 years years years * -3.2* -3.2* American Indian/Alaska Native All ages Birth to 49 years years years Hispanic All ages * * -3.0* -2.2* Birth to 49 years * 1.2* 1.2* years * -1.2* -0.9* 65 years * * -4.4* -3.3* AAPC indicates average annual percent change over the most recent 5 data years; APC, annual percent change based on incidence rates age adjusted to the 2000 US standard population. *The APC or AAPC is significantly different from zero (p < 0.05). Trends are based on cases diagnosed in CHSDA counties. Source: SEER program, Trends are based on incidence rates adjusted for delays in case reporting and were analyzed using the Joinpoint Regression Program, version , allowing up to 2 joinpoints. incidence is attributed to a higher prevalence of risk factors, such as obesity, unhealthy diet, and smoking, 26 while differences in screening are estimated to account for 40% of the racial disparity. 27 The larger mortality disparity reflects inequities in comorbidities, access to care and treatment, 28 and perhaps delayed follow-up of screendetected abnormalities. 29 It is important to recognize that the burden of CRC varies greatly within the broadly defined racial/ethnic groups presented in Figure 1. For example, Alaska Natives have CRC incidence (91.1 per 100,000) and mortality (36.7 per 100,000) rates that are about 80% higher than those in blacks and more than double those in other Native American groups combined, among whom rates are similar to NHWs. 6 CRC has been the most commonly diagnosed cancer in Alaska Natives since the early 1970s for reasons that are not well understood but may include a traditional diet high in animal fat and low in fruits and vegetables; vitamin D deficiency; and a high prevalence of smoking, obesity, and diabetes. 30,31 Alaska Natives, particularly rural residents, also have a high prevalence of Helicobacter pylori, 32 a bacterium primarily associated with inflammation and malignancy in the stomach, but that has also been associated with an increased risk of CRC in some studies. 33,34 Geographic disparities The striking variation in CRC incidence globally reflects the strong impact of lifestyle factors on the occurrence of this cancer. 35 Similarly, wide geographic disparities within the United States have shifted in recent decades. CRC death rates were highest across the Northeast and lowest in the South in the 1970s and 1980s, 36 whereas they are currently highest in parts of the South and Midwest and lowest in the West. 37 Table 2 shows annual, agestandardized CRC incidence and death rates by state and race/ethnicity. Geographic variation is similar by sex, with the highest rates for NHWs, NHBs, and Hispanics all in Southern states. Geographic patterns of CRC within the United States reflect differences in population demographics and the prevalence of risk factors, as well as the use of screening. VOLUME 67 _ NUMBER 3 _ MAY/JUNE

10 Colorectal Cancer Statistics, 2017 TABLE 8. CHARACTERISTIC Colorectal Cancer Screening (%), Adults Ages 50 Years or Older, United States, 2015 FECAL TEST* ENDOSCOPY COMBINED FECAL/ ENDOSCOPY Sex Men Women Age (years) Race/ethnicity Non-Hispanic white Non-Hispanic black Hispanic Non-Hispanic American Indian/ # Alaska Native Non-Hispanic Asian Education Some high school or less High school diploma or GED Some college/associates degree College graduate Sexual orientation Gay/lesbian # Straight Bisexual # Insurance status, ages years Uninsured Insured Immigration status Born in US Born in US territory # In US fewer than 10 years # In US 101 years Region Northeast Midwest South West Overall GED indicates General Education Development high school equivalency. *A fecal occult blood test (FOBT) or a fecal immunochemical test (FIT) within the past year. Sigmoidoscopy within the past 5 years or a colonoscopy within the past 10 years. An FOBT or FIT within the past year, or sigmoidoscopy within the past 5 years, or a colonoscopy within the past 10 years. Excludes Native Hawaiians or other Pacific Islanders. Individuals who had been in the United States for any length of time. #An estimate was not provided because of instability. Note: These estimates include diagnostic examinations. Estimates are age adjusted to the 2000 US standard population. Source: CDC. National Health Interview Survey, Public use data file. Subsite distribution Clinical and biologic characteristics, drug response and prognosis differ based on tumor location within the colorectum, suggesting distinct etiologic mechanisms As Table 3 indicates, the most common tumor location is the proximal colon (41%), followed by the rectum (28%). 8 However, there is striking variation in subsite distribution by sex and age (Fig. 2). Proximal tumor location is more likely in women than in men and increases with age. For example, 57% of CRCs in women aged 80 years and older occur in the proximal colon, versus just 26% in men younger than 50 years. Among men and women younger than 50 years, tumors are most commonly diagnosed in the rectum (41% and 36%, respectively). Survival and stage distribution CRC survival rates are presented for men and women combined because they do not vary substantially by sex. The 5- year relative survival rate for patients diagnosed from 2006 to 2012 (all followed through 2013) was 65%. 7 Survival declines to 58% at 10 years after diagnosis, although this estimate does not reflect the most recent improvements in detection and treatment because it is based on the experience of patients diagnosed as far back as Overall fiveyear survival is slightly higher for patients with rectal tumors (67%) than for those with colon tumors (64%), despite generally higher stage-specific survival for colon tumors, because rectal cancer is more often diagnosed at a localized stage (43% vs 38%) (Table 4). 7 Survival also varies based on tumor location within the colon; 5-year survival is higher for patients with distal tumors (69%) than for those with proximal tumors (65%). 6 Tumors in the proximal colon are associated with a higher risk of death, even after controlling for stage at diagnosis and treatment. 42 Survival is also higher in younger patients; 5-year survival is 69% in those younger than 65 years versus 62% in those aged 65 years and older. This age advantage is larger for those who have rectal tumors (72% vs 60%) than for those who have colon tumors (68% vs 62%). Localized stage CRC is diagnosed in 39% of patients, for which the 5-year survival rate is 90%. The survival rate declines to 71% and 14% for patients diagnosed with regional and distant-stage disease, respectively. 7 Black and AI/AN patients are most likely to be diagnosed with distantstage disease and have the lowest survival rates for every stage (Fig. 3). Disparities in CRC survival are largely driven by socioeconomic inequalities that result in differences in access to early detection tests and the receipt of timely, high-quality treatment Although black patients are less likely than others to receive appropriate surgery, adjuvant chemotherapy, and radiation treatments, survival is lower in black than in white patients even when treatment is equal. 50 A recent study found that tumor presentation at diagnosis played a larger role in survival differences than treatment, estimating that 40% of the racial disparity in colon cancer survival is because of the combined effects of later stage at diagnosis, a higher likelihood of unfavorable tumor characteristics, and more comorbidities among black patients. 51 Survival disparities are also evident within racial and ethnic groups. For example, blacks who are privately insured are 46% more likely 186 CA: A Cancer Journal for Clinicians

11 TABLE 9. State-Level Colorectal Cancer Incidence Rates and Trends ( ) and Screening Prevalence (2014), Adults Ages 50 Years or Older, United States INCIDENCE TREND 1 TREND 2 SCREENING INCIDENCE RATE ( ) YEARS APC YEARS APC AAPC AAPC RANK % 6 95% CI Alabama * -2.7* -2.7* Alaska * -4.1* -4.1* Arizona * -3.1* -3.1* Arkansas * * California * -3.2* -5.2* Colorado * * -2.8* Connecticut * -4.7* -4.7* Delaware * -5.6* -5.6* District of Columbia * -3.5* -3.5* Florida * -4.1* -4.1* Georgia * -3.0* -3.0* Hawaii * -2.2* -2.2* Idaho * -3.3* -3.3* Illinois * -3.7* -3.7* Indiana * -3.5* -3.5* Iowa * -3.6* -3.6* Kansas Data unavailable Kentucky * -2.6* -2.6* Louisiana * -2.5* -2.5* Maine * -5.7* -5.7* Maryland * -4.1* -4.1* Massachusetts * -5.4* -5.4* Michigan * -4.1* -4.9* Minnesota Data unavailable Mississippi * -1.7* -1.7* Missouri * -3.3* -3.3* Montana * -3.3* -3.3* Nebraska * -4.3* -6.0* Nevada Data unavailable New Hampshire * -4.6* -4.6* New Jersey * -3.8* -3.8* New Mexico Data unavailable New York * -4.0* -4.0* North Carolina * -4.5* -4.5* North Dakota * -2.7* -2.7* Ohio * -4.1* -4.1* Oklahoma * -2.7* -2.7* Oregon * -4.2* -4.2* Pennsylvania * -3.9* -3.9* Rhode Island * -5.7* -5.7* South Carolina * -4.6* -4.6* South Dakota * -2.9* -5.4* Tennessee * -3.8* -3.8* Texas * -3.6* -3.6* Utah * -3.6* -3.6* Vermont * -3.7* -3.7* Virginia * -4.3* -4.3* Washington * -3.8* -3.8* West Virginia * -3.1* -3.1* Wisconsin * -3.9* -3.9* Wyoming * -3.9* -3.9* % CI indicates 95% confidence interval; AAPC, average annual percent change over the most recent 5 data years; APC, annual percent change based on incidence rates age adjusted to the 2000 US standard population. Note: These trends are based on rates that were not adjusted for delays in case reporting, in contrast to Surveillance, Epidemiology, and End Results (SEER)- based trends. Trends were analyzed using the Joinpoint Regression Program, version , allowing up to 1 joinpoint. Incidence rates are per 100,000 and are age adjusted to the 2000 US standard population. Trends are unavailable for states that did not meet NAACCR high quality data standards for one or more years from 2004 to Screening prevalence reflects a fecal occult blood test within the past year, or sigmoidoscopy within the past 5 years, or colonoscopy within the past 10 years. *The trend is statistically significantly different from zero (p <.05) The incidence rate is for 2009 through These incidence rates are for 2009 through Sources: Incidence: NAACCR, Screening: Behavioral Risk Factor Surveillance System Public Use Data Tapes 2014, National Center for Disease Prevention and Health Promotion, Centers for Disease Control and Prevention. VOLUME 67 _ NUMBER 3 _ MAY/JUNE

12 Colorectal Cancer Statistics, 2017 FIGURE 6. Trend in Colorectal Cancer Mortality: Age-Standardized Rate Versus Number of Deaths, United States, Rates are age adjusted to the 2000 standard population. Source: NCHS, CDC, to survive 5 years after a CRC diagnosis than blacks who are uninsured. 52 Temporal Trends Incidence CRC incidence rates increased from 1975 through the mid- 1980s in both men and women but have since decreased with the exception of a slight, unexplained interruption from 1996 to 1998 (Fig. 4). 5 Some researchers have attributed the short-term increase, which also occurred in Canada, to the sudden rise in folate levels during the late 1990s after mandatory folic acid fortification of uncooked cereal grains was introduced to reduce the incidence of neural tube defects. 53,54 Folic acid appears to have a complex, paradoxical relation with CRC, in that it is associated with both prevention of new colonic neoplasia and promotion of existing neoplastic lesions. 55,56 Although prospective cohort studies find an inverse association between total dietary folate and CRC, 57,58 randomized controlled trials of folic acid supplements have shown an increased, although not statistically significant, risk of colorectal adenomas 59 and no effect on cancer occurrence. 60 Trends in CRC incidence are similar by sex but vary by age (Fig. 5). Incidence rates among individuals aged 50 years have dropped from a peak of (per 100,000) in 1985 to in The rate of decline accelerated around the year 2000, particularly in people aged 65 years, among whom rates plummeted from (per 100,000) in 2000 to in 2013 (incidence rate ratio [IRR], 0.63; 95% confidence interval [95% CI], ). During this time period, incidence in individuals aged 50 years declined by 32%, with reductions largest for distal tumors in those aged 65 years (IRR, 0.50; 95% CI, ) and smallest for rectal tumors in those ages 50 to 64 years (IRR, 0.91; 95% CI, in men; IRR, 1.00; 95% CI, in women). 6 This compares to 40% declines in rectal tumor incidence in ages 65 years (IRR, 0.62; 95% CI, in men; IRR, 0.59; 95% CI, in women). The age-specific annual percent change in incidence rates from 2000 to 2013 based on SEER data adjusted for delays in case reporting are shown by tumor location, stage at diagnosis, and race/ethnicity in Tables 5, 6, and 7, respectively. Over the past decade of data ( ), incidence rates decreased by an average of 1.4% per year among individuals ages 50 to 64 years and by 4.0% per year among those ages 65 years and older (Table 5). Among individuals ages 65 years and older, the rate of decline was similar regardless of tumor subsite, stage, or race/ethnicity (with the exception of AI/ANs). However, among people ages 50 to 64 years, declines were much slower for those with rectal tumors (Table 5), for distant-stage disease (Table 6), and for APIs and AI/ANs, among whom incidence rates were stable from 2000 through 2013 (Table 7). 188 CA: A Cancer Journal for Clinicians

13 FIGURE 7. Trends in Colorectal Cancer Mortality Rates by Race/Ethnicity, United States, *The APC or AAPC is significantly different from zero (p < 0.05). Trends for American Indian/Alaska Natives are based on mortality data from Contract Health Service Delivery Area counties. Source: NCHS, CDC, Trends were analyzed using the Joinpoint Regression Program, version , allowing up to 4 joinpoints. Trends by Hispanic ethnicity exclude deaths from Louisiana, New Hampshire, and Oklahoma. Differences in contemporary trends in individuals aged 50 years probably partly reflect differences in the uptake of screening. 61 NHIS data indicate that receipt of a colonoscopy in the past 10 years increased from 14% in 2000 to 41% in 2013 among individuals ages 50 to 54 years, from 16% to 52% in those ages 55 to 59 years, and from 25% to 63% in those ages 65 years and older. 62 From 2013 to 2015, screening with any guidelinerecommended test increased from 53% to 58% in individuals ages 50 to 64 years, from 65% to 68% in those ages 65 years and older, and from 59% to 63% in those ages 50 years and older combined (Table 8). This rise, which followed a plateau in screening from 2010 to 2013, translates into an additional 3,785,600 adults (ages 50 years and older) screened in If screening prevalence remains at the 2015 rather than the 2013 level, an estimated 39,700 additional CRC cases and 37,200 deaths will be prevented through CRC incidence in adults ages 50 years and older is declining rapidly in every state, although the rate appears to have stabilized in Arkansas in the most recent data years (Table 9). During 2009 through 2013, the average rate of decline exceeded 5% annually in 7 states (Nebraska, Maine, Rhode Island, Delaware, Massachusetts, South Dakota, and California). Notably, states with the highest incidence rates (Kentucky, Mississippi, and Louisiana) have among the slowest declines. Declines are also slow for rectal tumor incidence in individuals ages 50 to 64 years, among whom rates were stable in 31 of 46 states (with available data) and the District of Columbia. 63 The reported CRC screening prevalence in 2014 ranged from 76% in Massachusetts to 58% in Wyoming. In contrast to the downturns among screening-aged individuals, CRC incidence rates in adults aged <50 years rose by 1.6% from 2000 to 2013 (Table 5), for an overall increase of 22% (from 5.9 to 7.2 per 100,000; IRR, 1.22; 95% VOLUME 67 _ NUMBER 3 _ MAY/JUNE

14 Colorectal Cancer Statistics, 2017 FIGURE 8. Trends in 5-year Relative Survival Rates for Colorectal Cancer by Stage and Subsite, United States, Legend indicates diagnosis years. All patients followed through Source: SEER Program, SEER 9 registries, CI, ). The increase was driven solely by tumors in the distal colon (IRR, 1.24; 95% CI, ) and rectum (IRR, 1.22; 95% CI, ). 6 Incidence increased most rapidly for distant-stage disease, which rose by 3% per year during this time period (Table 6). The rise in early onset CRC occurred in all racial/ethnic groups except APIs (although the increase was not statistically significant in AI/ANs, likely because of small numbers); was largest among NHWs (2.3% per year from 2000 to 2013) (Table 7); and has also been reported in other high-income countries, including Norway, 64 Australia, 65 and Canada. 66 Although causes for this increase have yet to be elucidated, factors thought to have contributed include increased prevalence of excess body weight, as well as changes in lifestyle patterns that precipitated the obesity epidemic, including unhealthy dietary patterns and a sedentary lifestyle. 61,67-70 Mortality The declining trend in CRC mortality is more longstanding than that for incidence, particularly in women, among whom death rates have been decreasing since the mid-1940s (Fig. 4). In men and women combined, the death rate has dropped 51% from its peak of 28.6 (per 100,000) in 1976 to 14.1 in Mortality reductions through 2000 are attributed to improvements in treatment (12%), changing patterns in CRC risk factors (35%), and screening uptake (53%). 1 Similar to incidence, the decline in death rates accelerated beginning around 2000 and notably has been of sufficient magnitude to overcome the aging and growth of the population, such that the reported number of CRC deaths dropped from a peak of 57,644 in 1995 to 51,651 in 2014 (Fig. 6). From 2000 to 2014, CRC death rates decreased by 34% in individuals aged 50 years but increased by 13% in those aged <50 years (Fig. 5). CRC death rates have been decreasing since at least 1990 in whites, blacks, and APIs and since 2002 in Hispanics, with a similar pace of decline across these groups over the past decade of data. In contrast, death rates have remained stable in AI/ANs (Fig. 7). Progress in reducing CRC death rates has also lagged in the highest poverty areas of the United States, including the lower Mississippi Delta and parts of Appalachia. 36,71 Survival As of January 1, 2016, almost 1.5 million Americans were alive with a history of CRC. 72 Figure 8 depicts trends in survival for colon and rectal cancers separately since the mid-1970s based on data from the 9 oldest SEER registries. (Survival rates and stage distribution presented for the most current time period in this section differ slightly from those presented in Table 4, because they are based on a subset of SEER data with historical coverage.) From the mid-1970s to the most recent time period ( ), the 5-year relative survival rate for all stages combined increased from 51% to 66% for colon cancer and from 48% to 68% for rectal cancer. 7 These gains reflect improvements in treatment and earlier detection In the SEER 9 areas, the proportion of cases diagnosed at a localized stage increased from 30% during to 40% during for colon cancer and from 37% to 44% for rectal cancer. 76 Progress in survival may also reflect the increased use of advanced imaging techniques, such as positron emission tomography, which can improve the accuracy of staging and influence treatment decisions CA: A Cancer Journal for Clinicians

15 The largest improvement in survival has been for regional- and distant-stage disease. For example, the 5-year relative survival rate for regional-stage disease increased from 55% during to 74% during for patients with colon cancer and from 45% to 70% for those with rectal cancer (Fig. 8). This progress reflects important improvements in treatment, including adjuvant therapy for resectable stage III colon cancer, preoperative chemoradiation for locally advanced rectal cancer, 83,84 and cancerdirected surgery for advanced CRC. 85 Advances in the treatment of liver metastases, 86,87 new therapies (eg, antiepidermal growth factor receptor antibody therapy and bevacizumab), 88,89 and the use of imaging to improve detection of metastatic lesions 90 have particularly influenced the survival of patients with distant-stage disease. Between and , the 2-year relative survival rate for patients diagnosed with distant-stage tumors increased from 21% to 35% for colon cancer and from 22% to 39% for rectal cancer. 76 However, strides in the treatment of metastatic disease have been slower for black, Hispanic, and older patients 91,92 ; for certain molecular subtypes (eg, microsatellite instability-high and KRAS wild type) 93,94 ; and for patients with right-sided tumors. 41 Conclusions Despite dramatic reductions in CRC incidence and mortality overall, striking disparities by age, race, and tumor subsite remain. Reducing these inequalities and accelerating progress can be achieved by ensuring access to high-quality health care for all patients and incentivizing healthier lifestyles to prevent cancer occurrence. Healthy behaviors like achieving a normal body weight being physically active, and not consuming excessive alcohol or smoking can cut the risk of CRC by at least one-third Many more CRC cases and deaths could be prevented through increased screening. Meester and colleagues estimated that achieving the National Colorectal Cancer Roundtable s goal of increasing screening prevalence to 80% by 2018 would prevent 277,000 CRC cases and 203,000 deaths by Screening rates 75% in some states (Massachusetts, Rhode Island, and Maine) in 2014 and the increase nationally from 59% in 2013 to 63% in 2015 demonstrate real headway toward achieving the 80% goal. Finally, more research is needed to elucidate causes for the increasing burden of CRC in young adults and to advance treatments for tumor subtypes with low response rates to current therapies. Acknowledgments: We thank Iris Lansdorp for her technical assistance in estimating the additional cancer cases and deaths prevented as a result of the increase in screening prevalence. Author Contributions: Rebecca L. Siegel: Conceptualization, formal analysis, investigation, methodology, writing original draft, writing review and editing. Kimberly D. Miller: Formal analysis, investigation, methodology, and writing review and editing. Stacey A. Fedewa: Formal analysis, methodology, and writing review and editing. Dennis J. Ahnen: Writing review and editing. Reinier G.S. Meester: Formal analysis, methodology, and writing review and editing. Afsaneh Barzi: Writing review and editing. Ahmedin Jemal: Writing review and editing and supervision. References 1. Edwards BK, Ward E, Kohler BA, et al. Annual report to the nation on the status of cancer, , featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 2010;116: Vogelaar I, van Ballegooijen M, Schrag D, et al. How much can current interventions reduce colorectal cancer mortality in the US? Mortality projections for scenarios of risk-factor modification, screening, and treatment. Cancer. 2006;107: Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat Database: Mortality-All COD, Aggregated With State, Total US ( ) <Katrina/Rita Population Adjustment>. Bethesda, MD: National Cancer Institute, Division of Cancer Control and Population Sciences, Surveillance Research Program, Cancer Statistics Branch; 2016 (underlying mortality data provided by the National Vital Statistics System, 2016). 4. Wingo PA, Cardinez CJ, Landis SH, et al. Long-term trends in cancer mortality in the United States, Cancer. 2003; 97(suppl 12): Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat Database: Incidence-SEER 9 Regs Research Data (with SEER Delay Factors), Nov Sub ( ) <Katrina/Rita Population Adjustment>-Linked To County Attributes-Total US, Counties. Bethesda, MD: National Cancer Institute, Department of Cancer Control and Population Sciences, Surveillance Research Program, Surveillance Systems Branch; Surveillance, Epidemiology, and End Results (SEER) Program (seer.cancer.gov). SEER*Stat Database: Incidence-SEER 18 Regs Research Data with Delay- Adjustment, Malignant Only, Nov Sub ( ) <Katrina/Rita Population Adjustment>-Linked To County Attributes- Total US, Counties. Bethesda, MD: National Cancer Institute, Department of Cancer Control and Population Sciences, Surveillance Research Program, Surveillance Systems Branch; Howlader N, Noone AM, Krapcho M, et al, eds. SEER Cancer Statistics Review, Bethesda, MD: National Cancer Institute; Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat Database: North American Association of Central Cancer Registries (NAACCR) Incidence-Cancer in North America (CiNA) Analytic File, , for NHIA v2 Origin, Custom File With County, American Cancer Society (ACS) Facts and Figures Projection Project. Springfield, IL: NAACCR; Centers for Disease Control and Prevention. Behavioral Risk Factor Surveillance System Survey Data. Atlanta, GA: US Department of Health and Human Services; Centers for Disease Control and Prevention (CDC). Methodologic changes in the Behavioral Risk Factor Surveillance System in 2011 and potential effects on prevalence estimates. MMWR Morb Mortal Wkly Rep. 2012;61: National Center for Health Statistics. National Health Interview Survey, Public-use data file and documentation. Available at: cdc.gov/nchs/nhis/quest_ data_related_1997_forward.htm. Accessed July 16, Fedewa SA, Ma J, Sauer AG, et al. How many individuals will need to be screened to increase colorectal cancer screening prevalence to 80% by 2018? Cancer. 2015; 121: Chen HS, Portier K, Ghosh K, et al. Predicting US- and state-level cancer counts for the current calendar year: part I: evaluation of temporal projection methods for mortality. Cancer. 2012;118: Zhu L, Pickle LW, Ghosh K, et al. Predicting US- and state-level cancer counts for the current calendar year: part II: evaluation of spatiotemporal projection methods for incidence. Cancer. 2012;118: Fritz A, Percy C, Jack A, et al, eds. International Classification of Diseases for Oncology. 3rd ed. Geneva, Switzerland: World Health Organization; VOLUME 67 _ NUMBER 3 _ MAY/JUNE

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