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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Suggested Citation:"3 Cancer Epidemiology." National Academies of Sciences, Engineering, and Medicine. 2021. Diagnosing and Treating Adult Cancers and Associated Impairments. Washington, DC: The National Academies Press. doi: 10.17226/25956.
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Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

3 Cancer Epidemiology Cancer is the second leading cause of death in the United States af- ter heart disease (CDC, 2020a). In 2020 an estimated 1.8 million people received a new diagnosis of some form of cancer, and there were about 600,000 deaths (NCI, 2020a). Based on statistics from the National Can- cer Institute (NCI), the annual incidence (the number of people diagnosed with cancer each year) of all cancers is 442.2 per 100,000 individuals in the United States, and the number of cancer deaths (cancer mortality) is 158.5 per 100,000 individuals per year (based on 2013–2017 cases and deaths, respectively) (NCI, 2020a). In 1973, NCI established the Surveillance, Epidemiology, and End Results (SEER) Program, which collects and publishes cancer incidence and survival data from selected state cancer registries. SEER also routinely includes information on the race, ethnicity, age, sex, and geography of the cancer populations. The Centers for Disease Control and Prevention (CDC) administers the National Program of Cancer Registries, which compiles data from all 50 state-based cancer registries as well as the District of Columbia and Puerto Rico. In this chapter, the committee describes the incidence and mortality for common cancers in the U.S. adult population, based on SEER and National Program of Cancer Registries data. Although the committee recognizes that the U.S. Social Security Admin- istration (SSA) must assess long-term impairments and functional limita- tions that may result from having cancer or receiving treatment for it, the committee found that there is a dearth of national information on the inci- dence and prevalence of those impairments and limitations. For example, although an individual study may assess how many women in a research 47 PREPUBLICATION COPY—Uncorrected Proofs

48 DIAGNOSING AND TREATING ADULT CANCERS cohort develop lymphedema following a mastectomy, such data are not col- lected by any U.S. or state government or other organizational entity, and therefore the data that are available cannot necessarily be considered rep- resentative of the general population of women with breast cancer. Chapter 9 provides information about the cancer-related impairments (e.g., lymph- edema, cognitive impairments, and cardiotoxicity), whether resulting from the cancer or from its treatment, that may lead to functional limitations. The chapter begins with a discussion of cancer incidence, which is fol- lowed by a summary of cancer mortality statistics, and ends with a discus- sion of cancer survivorship and morbidity. Each section includes specific discussions of the epidemiology of breast cancer and lung cancer as well as limited epidemiologic information about other selected cancers where appropriate. The diagnosis and treatment of breast cancer and lung cancer may be found in Chapter 5 and Chapter 6, respectively. Further information on the changing epidemiology of and new treatments for the other common cancers of interest to SSA may be found in Chapter 7. CANCER INCIDENCE IN THE U.S. POPULATION Since 1992 the number of new cases of cancer diagnosed annually in the U.S. population has slowly but steadily declined, from 503 per 100,000 people to 415 per 100,000 people in 2017 (a 21% decrease); the annual number of deaths also declined during this period, from 213 per 100,000 to 149 per 100,000 (43% decrease). The most common cancers diagnosed in the United States are shown in Figure 3-1; their incidence differs somewhat between males and females (Siegel et al., 2020). The committee notes that non-melanoma skin cancers are by far the most common type of cancer, with the majority being basal and squamous cell skin cancers (ACS, 2020a). However, these cancers are rarely fatal or metastatic, and cancer registries do not typically track their incidence or mortality rates (Siegel et al., 2020); consequently, the committee does not discuss non-melanoma skin cancers further in this report. Comparing the 10 most common cancers listed in SSA disability claims (see Table 2-1) with those with the greatest incidence in the U.S. population (see Figure 3-1), it is evident that, while similar, the rankings of the most common cancers are not identical. Among the reasons for this divergence is that cancer is primarily a disease of aging and many who develop cancer are not eligible for SSA disability benefits. The median age at diagnosis for all cancers combined is 66 years, and most of those cancers with the great- est annual incidence have a median age of diagnosis of 65 years or older, including prostate cancer (median age 66 years) and melanoma (median age 65 years) (SEER, n.d.-c,-g,-h). Furthermore, some common cancers, such as PREPUBLICATION COPY—Uncorrected Proofs

CANCER EPIDEMIOLOGY 49 FIGURE 3-1 Estimated incidence (new cases) in 2020 for the 10 common cancers in men and women for all ages. SOURCE: Reprinted from Siegel, R.L., K.D. Miller, and A. Jemal. 2020. Cancer statistics, 2020. CA: A Cancer Journal for Clinicians 70(1):7–30; with permission from John Wiley and Sons. thyroid cancer, are often diagnosed at an early stage when the prognosis is excellent and have treatments that seldom lead to long-term impairments. In the sections below, the committee considers various factors that may affect trends in cancer incidence, including screening and diagnosis factors as well as changing population characteristics. This is followed by an overview of how demographic factors are reflected in cancer incidence rates. In the final sections, the committee looks specifically at factors that affect the incidence rates for breast cancer, lung cancer, and other selected cancers of interest to SSA. Factors Influencing Cancer Incidence Trends The incidence of the most common cancers in U.S. males and females has changed over the past several decades (see Figure 3-2). The incidence of lung and bronchus cancer and colorectal cancer has been decreasing in both adult men and women over the past 10 years, for example, whereas the incidence of other cancers such as melanoma and, to a lesser extent, thyroid cancer has increased in both sexes. These trends reflect changes in both the screening and diagnosis of cancer as well as changes in health behaviors. Public health efforts such as reducing tobacco use, vaccina- tion against the human papillomavirus (HPV), and the use of screening and removal of precancerous lesions have all contributed to the reduced incidence for some cancers. For example, lung cancer incidence across age groups has decreased as tobacco control efforts over the last 50 years have reduced smoking by about 2% per year in the United States (Ng et al., PREPUBLICATION COPY—Uncorrected Proofs

50 DIAGNOSING AND TREATING ADULT CANCERS 2014), leading to a notable decline in lung cancer incidence, particularly among men. However, other health behaviors such as the growing number of people, including young people, who are overweight or obese may result in an increase in some other cancers such as multiple myeloma and kidney cancer (Sung et al., 2019). The decline in colorectal cancer incidence in the general population may be due to the removal of precancerous lesions dur- ing screening sigmoidoscopy and colonoscopy (Araghi et al., 2019); how- ever, some recent studies have reported an increase in early onset colorectal cancer in adults younger than 50 years of age, which could partly reflect the obesity epidemic and also poor diet quality (Sung et al., 2019). As shown in Figure 3-2, prostate cancer incidence rose dramatically in the early 1990s—a rise that was due in large part to widespread screening with the prostate specific antigen test, which often found slow-growing and indolent cancers that would not become clinically evident or poten- tially lead to death without screening. Prostate cancer incidence has since declined, as national guidelines no longer recommend routine prostate specific antigen testing for all populations, thus reducing the diagnosis of slow-growing cancer (USPSTF, 2018). Similarly, the incidence of breast can- cer increased in the 1980s as mammography screening was adopted widely and expanded to women in their 40s; it increased again in the late 1990s and early 2000s, which has been attributed to use of hormone replacement therapy (Silverman et al., 2011), and it declined somewhat after about 2005 with the publication of high-quality evidence against the routine use of postmenopausal hormone therapy (Rossouw et al., 2002). More informa- tion on cancer screening and diagnosis can be found in Chapter 4. Of particular relevance to SSA are the changing patterns of cancer diag- nosis for young adults (typically aged 20–49 years), given that these work- ing adults may have potentially greater long-term financial needs should they become disabled. The 2019 Annual Report to the Nation on Cancer, prepared by the American Cancer Society, CDC, NCI, and the North Amer- ican Association of Central Cancer Registries, focused on adults aged 20– 49 years. It showed that in this age group during 2011–2015 the incidence of all invasive cancers combined decreased 0.7% among men but increased 1.3% among women, largely driven by the increased incidence of breast cancer. The overall cancer incidence rates during this period were substan- tially lower among men (115.3 per 100,000) than among women (203.3 per 100,000). The cancers with the highest incidence rates (per 100,000) among men were colon and rectum (13.1), testis (10.7), and melanoma of the skin (9.8) and among women were breast (73.2), thyroid (28.4), and melanoma of the skin (14.1) (Ward et al., 2019). A recent cross-sectional study of a slightly younger cohort of adolescents and young adults aged 15 to 39 years, found that the diagnosis of several cancers in this popula- tion increased between 1973 and 2015, particularly for carcinomas of the PREPUBLICATION COPY—Uncorrected Proofs

CANCER EPIDEMIOLOGY 51 FIGURE 3-2 Trends in U.S. incidence rates for selected cancers by sex and all ages, 1975–2016. Rates are age adjusted to the 2000 U.S. standard population and ad- justed for delays in reporting. Estimates are rounded to the nearest 10 and exclude basal cell and squamous cell skin cancers and in situ carcinoma except urinary bladder. Ranking is based on modeled projections and may differ from the most recent observed data. NOTE: * Includes intrahepatic bile duct. SOURCE: Reprinted from Siegel, R.L., K.D. Miller, and A. Jemal. 2020. Cancer statistics, 2020. CA: A Cancer Journal for Clinicians 70(1):7–30; with permission from John Wiley and Sons. kidney, thyroid, gastrointestinal tract (e.g., carcinoma of the colon and rectum), germ cell and trophoblastic neoplasms (e.g., testicular cancer), and melanoma. During this period, the rate of cancer increased by 29.6%, from 57.2 to 74.2 invasive cancer diagnoses per 100,000 adolescents and young adults per year (Scott et al., 2020). Another analysis of SEER data from 1975 to 2015 found that the incidence of esophageal cancers increased by 2.9% per year for adults under 50 years of age; furthermore, these younger adults typically presented with more advanced disease than older adults and had a poorer prognosis (Codipilly et al., 2020). Because screening for breast cancer does not begin until age 40, many younger women who are diagnosed with breast cancer have larger tumors and often require more complex and toxic therapies that may extend over several years. The same is true for colorectal cancer, where screening for average-risk individuals has started at age 50, although recent recommendations suggest starting at age 45 (USPSTF, 2020). Obesity is an important factor that may be influencing patterns of cancer incidence, especially in young adults. Sung et al. (2019) examined PREPUBLICATION COPY—Uncorrected Proofs

52 DIAGNOSING AND TREATING ADULT CANCERS cancer incidence between 1995 and 2014 using data from 25 state cancer registries. Increases in cancer incidence among young adults aged 25–49 years were seen for 6 of 12 cancers considered to be obesity related (multi- ple myeloma, colorectal, uterine corpus, gallbladder, kidney, and pancreatic cancer). When the data were analyzed by generation, these increases were found to be steeper among successively younger generations. Conversely, during this period the cancer incidence in young adults increased for only two of 18 cancers not associated with obesity (gastric cancer and leukemia). Cancers associated with HPV are also more common in younger pa- tients, and some types of HPV-associated cancers are increasing in fre- quency. In the United States, high-risk HPVs (primarily HPV 16 and HPV 18) cause 3% of all cancers in women and 2% of all cancers in men (NCI, 2020b). There are about 45,300 new cases of cancer in parts of the body where HPV is often found, and HPV is estimated to cause about 35,900 cancers each year (CDC, 2020b). HPV-related cancers include virtually all cervical cancers, more than 90% of anal cancers, 60% of penile cancers, 75% of vaginal cancers, and 70% of vulvar cancers as well as 70% of oropharyngeal cancers (Jemal et al., 2013). Demographic Factors The risk of developing cancer is influenced by many factors, including demographic characteristics. In this section, the committee provides an overview of differences in cancer incidence that are evident across age, sex, and ethnic and racial groups for commonly diagnosed cancers. The impact of geographic location on the incidence of cancers is also briefly consid- ered, followed by brief discussions of breast cancer, lung cancer, and other frequently diagnosed cancers that may be of interest to SSA. Age Advancing age is the most important risk factor for cancer overall and also for many individual cancers (NCI, 2015). The development of cancer occurs over several decades, influenced by internal exposures (e.g., male and female hormones) or exogenous exposures (e.g., sunburn or tobacco use) that stimulate cells to overgrow and acquire mutations that give cells a growth advantage, ultimately leading to precancerous and then cancerous changes. For some cancers, screening and early detection can identify these precancerous changes so that they can be removed, but ultimately many cancers that are initiated in youth or midlife (e.g., colon adenomas) may not be detected until 10 or more years later. The incidence of most adult cancers increases with age, including those for which SSA receives the most disability claims (see Figure 3-3), although this association is stronger for PREPUBLICATION COPY—Uncorrected Proofs

CANCER EPIDEMIOLOGY 53 450 400 350 Lung and bronchus Incidence per 100,000 300 Breast* Colon, rectum, or anus 250 Oral cavity and pharynx 200 Pancreas Brain and other nervous system 150 Leukemia 100 Lymphoma 50 Liver and intrahepatic bile duct Ovary* 0 Age at Diagnosis FIGURE 3-3 Cancer incidence by age at diagnosis for 10 cancer sites with highest SSA claims, 2013–2017. Dotted line represents age at which most people are no longer eligible for SSA disability benefits. NOTE: * Breast and ovarian cancer incidence are estimated from sex-specific in- cidence, with the assumption that the population is 50% male and 50% female. SOURCE: Based on SEER Cancer Statistics Review 1975–2017. https://seer.cancer. gov/cgi-bin/csr/1975_2017/search.pl (accessed October 19, 2020). some cancers (e.g., lung, breast, colon cancers) than for others (e.g., ovary, liver, and brain cancers). While cancer is primarily a disease of older adults, there are some cancers that are more commonly diagnosed among younger adults; for example, the median age at diagnosis of cancer of the testis is 33 years (SEER, n.d.-i), the median age of diagnosis for Hodgkin lymphoma is 39.5 years, and more than half of all acute lymphocytic leukemia diagnoses are in people under 17 years of age (Howlader et al., 2020b). As seen in Table 3-1, about half of the common cancers for which SSA receives disability claims have a median age of diagnosis at or above the age of 65. Race/Ethnicity and Sex Cancer incidence rates vary by race and ethnicity (see Figure 3-4). Overall, Whites and Blacks have the highest cancer incidence rates, and Asian/Pacific Islanders and American Indian/Alaska Natives have the low- est incidence rates. Moreover, there is substantial variability in the incidence rates for spe- cific cancers by sex and race/ethnicity (see Figure 3-5). Not including those cancers that occur predominately in one sex (e.g., breast and cancers of the reproductive organs), most cancers occur more commonly in men than PREPUBLICATION COPY—Uncorrected Proofs

54 DIAGNOSING AND TREATING ADULT CANCERS TABLE 3-1 Median Age at Diagnosis for Selected Cancers, 2013–2017 Cancer Total Males Females Lung 71 70 71 Breast 63 68 62 Colorectal 67 66 68 Oral cavity and pharynx 63 63 65 Pancreas 70 69 72 Brain and other nervous system 59 59 60 Leukemia 67 67 67 Lymphoma 66 65 66 Liver and intrahepatic bile duct 65 64 68 Ovary 63 — 63 Melanoma of the skin 65 67 61 SOURCE: Howlader et al., 2020a. women; this is true in all race categories, aside from the case of lymphoma in American Indian/Alaskan Natives, where the incidence rates are almost identical between the sexes. White men and women have the greatest inci- dence rates for breast cancer, head and neck cancers, nervous system cancers, leukemia, lymphoma, and ovarian cancer, and Black men and women have the greatest incidence rates for lung cancer and colorectal cancers. American Indian/Alaskan Natives and Asian/Pacific Islanders of both sexes generally have lower incidence rates overall, though American Indian/Alaskan Natives have the highest incidence rates of liver and bile duct cancers. FIGURE 3-4 Estimated 2019 cancer incidence rates by race and ethnicity for all cancers for all ages. NOTES: a Asian/Pacific Islander; b American Indian/Alaska Native. SOURCE: SEER, n.d.-c. PREPUBLICATION COPY—Uncorrected Proofs

140 130.5 124 118.1 115.3 120 100.1 97.2 91.5 100 79.5 79.15 77.2 77 74.5 80 68.8 64.8 60 60 42 40 36.8 31 30.8 30.6 Incidence per 100,000 30.2 28.4 27.6 27.1 26.6 24.7 23.3 23.1 22.5 22.3 21.7 20.2 19.7 18.2 17.6 16.8 16.7 16.6 16.4 14.3 14.3 11.7 20 10.4 10.3 9.5 9.1 8.4 7.8 7.7 6.9 0 Black Black Black Black Black Black Black Black Black Black AI/AN AI/AN AI/AN AI/AN AI/AN AI/AN AI/AN AI/AN AI/AN AI/AN White White White White White White White White White White Asian/PI Asian/PI Asian/PI Asian/PI Asian/PI Asian/PI Asian/PI Asian/PI Asian/PI Asian/PI Hispanic Hispanic Hispanic Hispanic Hispanic Hispanic Hispanic Hispanic Hispanic Hispanic Lung Cancer Breast Cancer Colorectal Head and Neck Pancreatic Nervous Leukemia Lymphoma Liver and Bile Ovarian Cancers Cancers Cancer System Cancers Ducts Cancer Cancer MALE FEMALE FIGURE 3-5 10 most common cancers listed in SSA disability claims in 2019 and their incidence by race/ethnicity for all ages (number of new cases per 100,000 individuals). NOTE: Race categories may not be mutually exclusive; Hispanic is not mutually exclusive from Whites, Blacks, Asian/Pacific Island- PREPUBLICATION COPY—Uncorrected Proofs ers, and American Indians/Alaska Natives. SOURCES: Based on SEER Cancer Statistics Review (CSR) 1975–2017. https://seer.cancer.gov/cgi-bin/csr/1975_2017/search.pl (ac- cessed October 19, 2020). 55

56 DIAGNOSING AND TREATING ADULT CANCERS Geographic Differences Cancer incidence varies across the United States. For example, lung cancer incidence rates are higher in the South and Midwest than in the Northeast and West and also are higher in rural than in urban counties. These differences may reflect patterns of smoking; such regional and be- havioral factors can affect patterns of cancer incidence by race/ethnicity (Houston et al., 2014, 2018). Cancer incidence may also vary with geographic differences in can- cer screening. For example, state-level incidence rates for hormone-recep- tor-positive breast cancer correlate with the state rate of mammography (Kohler et al., 2015). Recent data show that from 2012 through 2016, cancer incidence rates decreased in 31 states and were stable in 15 states (Henley et al., 2020). Breast Cancer Breast cancer is the most frequent diagnosis given in SSA cancer dis- ability claims (see Table 2-1) and the most commonly diagnosed cancer in women (see Figure 3-1). According to estimates by SEER, there were 276,480 new breast cancer cases in the United States in 2020 (SEER, n.d.- e). Although breast cancer is also diagnosed in men, it is rare, with only about 2,600 estimated new cases in 2020 (Siegel et al., 2020). As noted in Table 3-1, the median age at diagnosis of breast cancer is 63 years, and thus more than half of women diagnosed with this cancer are of working age. Approximately 12.9% of women will be diagnosed with breast can- cer at some point during their lifetime (SEER, n.d.-e). Importantly, many women and men diagnosed with breast cancer are successfully treated. It is estimated that about 3.8 million women and men with a past or current diagnosis of breast cancer are alive in the United States (Miller et al., 2019). Breast cancer incidence has been rising at an average rate of 0.3% each year over the last 10 years (Siegel et al., 2020), especially in younger women (Ward et al., 2019). More than 55% of breast cancer is diagnosed in women aged 64 years or younger (SEER, n.d.-e). Breast cancer has an annual incidence rate of 76.7 per 100,000 persons for women aged 55–59 years and 89.5 per 100,000 persons for women aged 60–64 years (How- lader et al., 2020b). Breast cancer affects women of all races and ethnicities, although it is more frequently diagnosed in White and Black women (incidence 131.3/100,000 persons and 124.8/100,000 persons, respectively), fol- lowed by Asian/Pacific Islanders (102.9/100,000 persons), and Hispanics (99.1/100,000 persons), with American Indian/Alaskan Native women hav- ing the lowest incidence of breast cancer diagnosis (79.5/100,000 persons) PREPUBLICATION COPY—Uncorrected Proofs

CANCER EPIDEMIOLOGY 57 TABLE 3-2 Age-Adjusted SEER Incidence Rates (per 100,000 persons) for Invasive Breast Cancer, 2013–2017 Age at Diagnosis White Females Black Females All ages 131.3 124.8 Under 65 85.5 83.9 65 and over 447.7 407.5 SOURCE: Howlader et al., 2020b. (Howlader et al., 2020b). Overall, Black women have a slightly lower inci- dence of breast cancer than White women, although this varies by age, with the incidence slightly higher for Black than White women who are younger than age 65 and higher for White than Black women older than age 65 (see Table 3-2). Breast cancers in Black women tend to have less favorable prognostic characteristics than those in White women. Lung Cancer Lung cancer is the second most frequent cancer diagnosis in SSA cancer disability claims (see Table 2-1) and the second most commonly diagnosed cancer for both men and women in the United States (see Figure 3-1). In 2020 an estimated 228,820 American adults were diagnosed with new cases of lung cancer (Siegel et al., 2020). About one-third of lung cancer diagnoses are made in people younger than 65, primarily those aged 55–64 years (SEER, n.d.-f). Smoking, a main cause of both major types of lung cancer—non-small- cell lung cancer (NSCLC) and small-cell lung cancer (SCLC)—contributes to an estimated 90% of lung cancer deaths (ALA, 2020). A decline in the number of smokers in the U.S. adult population has contributed to fewer new cases of lung cancer. In 1965 over 40% of American adults smoked cigarettes, but by 2018 this number had dropped to 13.7% (ALA, 2020). In smokers the latency period between exposure to the carcinogens in tobacco and a lung cancer diagnosis is estimated to be 20 years (Alberg et al., 2013). Not all lung cancers, however, are associated with smoking, and people who have never smoked can develop lung cancer (Alberg et al., 2013). See Chapter 6 for more information on the risk factors for lung cancer. Lung cancer incidence is higher for men than for women: Of the 228,820 new cases of lung cancer in 2020, it is estimated that 116,300 cases were in men and 112,520 in women (see Figure 3-1). Notably, trends show the incidence of NSCLC dropping at a greater rate among men (3.1%, 2008–2016) than among women (1.5%, 2006–2016). The incidence rates of SCLC also dropped between 2001 and 2016 for both men (3.6%) and PREPUBLICATION COPY—Uncorrected Proofs

58 DIAGNOSING AND TREATING ADULT CANCERS TABLE 3-3 Age-Adjusted SEER Incidence Rates (per 100,000 persons) for Lung and Bronchus Cancer, 2013–2017 Whites Blacks Age at Diagnosis Both Sexes Males Females Both Sexes Males Females All ages 56.0 62.2 51.5 54.8 71.2 43.8 Under 65 16.2 16.5 16.0 19.7 23.3 16.7 65 and over 331.3 378.2 297.2 297.7 402.7 231.1 SOURCE: Howlader et al., 2020b. women (2.7%) (Howlader et al., 2020a). Black men are more likely to de- velop lung cancer than White men, but Black women have lower incidence rates of lung cancer than White women, especially those aged 65 and older (see Table 3-3). Lung cancer incidence rates vary across geographic regions in the United States, with the highest incidence rates generally in the South and the lowest incidence rates in the West. These incidence rates generally mir- ror the prevalence of tobacco use in these regions of the country (Schabath and Cote, 2019). Other Selected Cancers As shown in Table 3-1, SSA receives disability claims for a number of cancers that do not necessarily correspond in terms of frequency with those seen in the general U.S. population (see Figure 3-1). Although the com- mittee was asked to focus on breast and lung cancer, it was also asked to discuss other cancers as appropriate. As such, the committee also comments on other cancers that are prevalent and among the leading cancer diagnoses received by SSA: gastrointestinal cancers (colorectal cancer, pancreatic can- cer, and liver and bile duct cancers), hematologic cancers (leukemias, lym- phomas, and myelomas), head and neck cancers, and ovarian cancer (see Table 2-1). The committee also discusses melanoma, which is not among the SSA top 10 cancers, but for which there are novel treatments that may have long-term impacts on its future incidence and outcomes. SSA included cancers of the nervous system in its impairment listings (SSA, 2020); however, brain tumors are relatively uncommon cancers in the U.S. population, ranking 16th in frequency (SEER, n.d.-b). Central nervous system cancers are slightly more common in men than women and slightly more common among those with certain genetic syndromes. They are also more common among Whites than other racial or ethnic groups (SEER, n.d.-b) (see Figure 3-5). Epidemiologic and other information about these cancers, including mela- noma, which is not among the common cancers for which SSA receives disability PREPUBLICATION COPY—Uncorrected Proofs

CANCER EPIDEMIOLOGY 59 claims, but excluding cancers of the nervous system, is provided in Chapter 7. Refer to Table 3-1 for the median ages of diagnoses for these cancers. CANCER MORTALITY Cancer mortality refers to deaths due to cancer. The cancer mortality rate is the number of deaths from cancer among a specified population (e.g., number of deaths per 100,000 population) (SEER, n.d.-a). Although cancer is the second leading cause of death in the United States (heart disease is the leading cause), the cancers that result in the greatest mortality are not necessarily those with the greatest incidence. Table 3-4 shows the difference in the incidence and mortality rates for the 10 most frequent cancer diag- noses in the SSA disability claims (see Table 2-1). For example, although breast cancer has an incidence rate more than twice that of lung cancer, its mortality rate is less than half that of lung cancer. On the other hand, both pancreatic cancer and nervous system cancers have similar incidence and mortality rates. Figure 3-6 shows the estimated mortality for different types of cancer in the United States. As was seen with the cancers in SSA disability claims, the incidence rates and mortality rates for the most common cancers in the United States are not necessarily correlated; for example, ovarian cancer is the fifth most frequent cause of cancer death among women, but not in the TABLE 3-4 Incidence and Mortality Rates (per 100,000 persons) for the 10 Most Common Cancers Listed in SSA Disability Claims Received in 2019 Impairment Incidence Ratea Mortality Ratea Lung cancer 54.2 38.5 Breast cancer 127.5 20.6 Colorectal cancers 38.2 13.7 Head and neck cancers 11.4 2.5 Pancreatic cancer 13.1 11.0 Nervous system cancers 6.4 4.4 Leukemia 14.1 6.3 Lymphoma (non-Hodgkin lymphoma) 19.6 5.4 Liver or bile ducts cancers 9.0 6.6 Ovarian cancer 11.2 6.7 a All incidence and mortality rates are for both men and women combined (except for breast and ovary which are solely for women) and age-adjusted based on SEER data for 2013–2017. SOURCE: Howlader et al., 2020b. PREPUBLICATION COPY—Uncorrected Proofs

60 DIAGNOSING AND TREATING ADULT CANCERS FIGURE 3-6 Estimated mortality (deaths) for the 10 common cancers in men and women for all ages in 2020. SOURCE: Reprinted from Siegel, R.L., K.D. Miller, and A. Jemal. 2020. Cancer statistics, 2020. CA: A Cancer Journal for Clinicians 70(1):7–30; with permission from John Wiley and Sons. top 10 most frequently diagnosed cancers (see Figure 3-1). Additionally, while esophageal cancer represents only 1% of all new cancer cases, is the seventh leading cause of cancer death for men, and eleventh overall (SEER, n.d.-d). Cancer mortality rates have fallen since 1991 (see Figure 3-7), driven primarily by declines in mortality rates for the four leading cancers (breast, lung, colorectal, and prostate). A recent report highlights some important FIGURE 3-7 U.S. mortality rates for heart disease compared with cancer by age at death, 1975–2017. NOTES: Data from U.S. Mortality Files, National Center for Health Statistics, Cen- ters for Disease Control and Prevention. Rates are per 100,000 and age-adjusted to the 2000 U.S. standard population. SOURCE: Howlader et al., 2020b. PREPUBLICATION COPY—Uncorrected Proofs

CANCER EPIDEMIOLOGY 61 trends, including a rapid decline in death from lung cancer, with the larg- est ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017 (Siegel et al., 2020), which likely due to recent advances in therapies for metastatic disease. The report also highlights a decrease in deaths from melanoma of the skin, which is also likely due to the availability of effective new therapies. More information regarding these treatment advances for these cancers can be found in Chapters 5, 6, and 7. Demographic Factors The committee considered several factors that influence mortality rates for cancer, including age, sex, and race/ethnicity. Overall, from 2013 through 2017 cancer death rates decreased in all states, decreasing 4.3% per year in Alaska and ≥2% per year in six additional states (Arizona, Connecticut, Massachusetts, New Jersey, New York, and Wyoming) and the District of Columbia (Henley et al., 2020). Age The mortality rates by age at death for the most common SSA cancers are shown in Figure 3-8. Similar to the trends in incidence, the mortality of most adult cancers increases with age, with notable increases in the 350 300 Lung and bronchus 250 Mortality per 100,000 Breast* Colon, rectum, or anus 200 Oral cavity and pharynx 150 Pancreas Brain and other nervous system 100 Leukemia 50 Lymphoma Liver and intrahepatic bile duct 0 Ovary* Age at Death FIGURE 3-8 Cancer-specific mortality by age at death for 10 cancer sites with highest SSA claims, 2013–2017. Dotted line is the age at which most people are no longer eligible for SSA disability benefits. * Breast and ovarian cancer incidence are estimated from sex-specific incidence, with the assumption that the population is 50% male and 50% female. SOURCE: Based on SEER Cancer Statistics Review 1975–2017. https://seer.cancer. gov/cgi-bin/csr/1975_2017/search.pl (accessed October 19, 2020). PREPUBLICATION COPY—Uncorrected Proofs

62 DIAGNOSING AND TREATING ADULT CANCERS mortality rates for lung, colorectal, and pancreatic cancer in those aged 65 years and older. The median age at death across all cancers is 72 years, although this varies by cancer type (SEER, n.d.-c); for example, brain and other nervous system cancers have a median age of death of 65. Race/Ethnicity and Sex The mortality rate per 100,000 adults aged 20–49 years for all cancers combined for 2012–2016 was 22.8 among men and 27.1 among women. During the same time period, mortality rates decreased 2.3% per year among men and 1.7% per year among women (Ward et al., 2019). How- ever, among all adults the number of cancer deaths (cancer mortality) is 158.3 per 100,000 men and women per year (based on 2013–2017 cases and deaths, respectively). Cancer mortality is higher among men than women (189.5 per 100,000 men and 135.7 per 100,000 women) (NCI, 2020a). When comparing groups based on race/ethnicity and sex, cancer mortality is highest in Black men (227.3 per 100,000) and lowest in Asian/ Pacific Islander women (85.6 per 100,000) (NCI, 2020a). Breast Cancer Breast cancer is the second leading cause of death among women in the United States, with an estimated 42,170 deaths in 2020 (see Figure 3-6), and it is the fourth leading cause of cancer death overall (SEER, n.d.-e). Black women have a higher age-adjusted mortality rate (27.3 per 100,000) than White women (19.6 per 100,000), while Asian/Pacific Islander women have the lowest death rate (11.7 per 100,000) (SEER, n.d.-e). Female breast cancer age-adjusted mortality rates have been steadily decreasing since 1995, dropping from 30.55 per 100,000 to 19.88 per 100, 000 in 2017. Mortality increases with age for female breast cancer: the age-adjusted breast cancer mortality rate for women under 65 is 9.9 per 100,000, while the age-adjusted breast cancer mortality rate for women 65 and older is 92.6 per 100,000, based on SEER data from 2013–2017 (see Table 3-5). TABLE 3-5 Age-Adjusted SEER Mortality Rates (per 100,000 persons) for Invasive Breast Cancer, 2013–2017 Age at Death White Females Black Females All ages 19.8 27.6 Under 65 9.2 15.5 65 and over 91.3 111.7 SOURCE: Howlader et al., 2020b. PREPUBLICATION COPY—Uncorrected Proofs

CANCER EPIDEMIOLOGY 63 Male breast cancer is rare compared with female cancer, and it is es- timated that 520 men will die from breast cancer in 2020 (there will be an estimated 2,620 new diagnoses of breast cancer in men in 2020) (ACS, 2020b). Age is also primary risk factor for male breast cancer; the age-ad- justed breast cancer death rate for men under 65 is 0.1 per 100,000, while the age-adjusted breast cancer death rate for men 65 and older is 1.6 per 100,000, based on SEER data from 2013–2017 (Howlader et al., 2020b). More information on breast cancer screening, diagnosis, treatment, and prognosis is included in Chapter 5. Lung Cancer Lung cancer is the leading cause of cancer death in the United States, regardless of gender, race, or ethnicity. In 2020 an estimated 135,720 deaths will be due to lung cancer (SEER, n.d.-f) (see Figure 3-6). The mortality rate for lung cancer is higher for men than for women, and Black men have higher lung cancer mortality rates than White men, although Black and White women have similar mortality rates (see Table 3-6). Lung cancer mortality rates have been dropping over time, from a high of 59.1 per 100,000 persons in 1993 to 36.79 per 100,000 persons in 2017 (Howlader et al., 2020b), primarily as a consequence of declining tobacco use (see incidence data above), but also due to recent advances in lung cancer care. Much of this decline in mortality is the result of decreases in mortality from NSCLC, for which the mortality rates declined by 6.3% annually from 2013 through 2016 for men and by 5.9% for women from 2014 through 2016. In contrast, mortality from SCLC declined for both men and women (4.3% and 3.7%, respectively) between 2006 and 2016, almost entirely as a result of declining incidence (Howlader et al., 2020a). More information on lung cancer screening, diagnosis, treatment, and prognosis may be found in Chapter 6. TABLE 3-6 Age-Adjusted SEER Mortality Rates (per 100,000 persons) for Lung Cancer, 2013–2017 Whites Blacks Age at Death Both Sexes Males Females Both Sexes Males Females All ages 41.0 49.4 34.5 42.3 58.8 31.1 Under 65 11.1 12.5 9.8 13.4 17.3 10.1 65 and over 248.0 304.8 205.6 242.1 346.2 175.8 SOURCE: Howlader et al., 2020b. PREPUBLICATION COPY—Uncorrected Proofs

64 DIAGNOSING AND TREATING ADULT CANCERS CANCER SURVIVAL Cancer survival refers to the length of time after a cancer diagnosis that an individual remains alive. A survival rate is the number of individuals alive among all individuals diagnosed with cancer at a particular time (e.g., 5 years after diagnosis) (NCI, 2011). The 5-year survival rate for all cancers has increased from 48.9% for people diagnosed with cancer in 1975–1977 to 69.5% for those diagnosed with cancer in 2010–2016 (Howlader et al., 2020b). Survival rates should be interpreted with caution as they may sug- gest an increase in survival that is actually the result of how a population is categorized. For example, if there are changes in who is being diagnosed with cancer, as may occur with new screening programs that differentially identify people with small and slow-growing or nonprogressive tumors, it may appear that more people are surviving with the cancer when they were unlikely to have died of the cancer during a specific period of time to begin with (Ellis et al., 2014). Nevertheless, cancer survival rates are often used to express the likelihood that a newly diagnosed cancer patient will be alive for a specified period of time (e.g., 1 year, 5 years, or 10 years); 5-year survival rates are the most commonly reported values. In 2019 there were an estimated 16.9 million cancer survivors in the United States, of whom about one-third were younger than 65 years of age (Miller et al., 2019). The number of cancer survivors is expected to increase to over 26 million by 2040 (Bluethmann et al., 2016) (see Figure 3-9). There are many reasons why the number of individuals living for ex- tended periods of time after a cancer diagnosis should increase: screening that detects precancerous tissue; earlier diagnosis (small tumors that have not spread from a local site); more effective and curative initial treat- ments; and prolonged control of disease that is widespread in the body. Furthermore, the growth of the U.S. population leads to larger numbers of individuals in each age group who are at risk for cancer. Improvements in survival mean that more people are living longer with cancer. Similar to cancer mortality, cancer-specific survival rates for many cancers have improved over the years, although there are often substantial differences in survival rates across cancer types. These differences can be explained in part by the disease stage at diagnosis. Survival rates tend to be better for cancers that are confined to the tissue of origin (i.e., localized disease), whereas cancers that are typically diagnosed at more advanced stages tend to have poorer survival rates. Figure 3-10 shows 5-year survival rates by cancer type and stage for the cancers found most frequently in SSA disability claims. However, there is considerable variation in the frequency of localized disease across these cancers. For example, lung cancer is seldom localized at the time of diagnosis and has a poorer 5-year survival rate even when it is localized compared with localized or regional breast cancer. In contrast, breast cancer is almost always localized at the time of diagnosis and thus has an extremely favorable 5-year survival rate. PREPUBLICATION COPY—Uncorrected Proofs

CANCER EPIDEMIOLOGY 65 FIGURE 3-9 Cancer prevalence and projections in the U.S. population from 1975–2040. SOURCE: Adapted from Bluethmann, S.M., A.B. Mariotto, and J.H. Rowland. 2016. Anticipating the “silver tsunami”: Prevalence trajectories and comorbidity burden among older cancer survivors in the United States. Cancer Epidemiology Biomarkers & Prevention 25(7):1029–1036. Copyright © 2016, with permission from American Association for Cancer Research. 100 99 92 90 90 90 86 84 84 80 71 72 75 75 5-Year Survuval (%) 70 64 65 66 63 65 57 60 48 50 39 39 37 40 31 33 27 29 30 19 18 20 14 12 11 9 10 5 3 2 0 Overall Localized Regional Distant FIGURE 3-10 Five-year cancer-specific survival percentages based on stage at diag- nosis for all ages, SEER data 2009–2012. NOTE: Lymphoma is for non-Hodgkin lymphoma only. SOURCE: Data from Siegel et al. (2020), although cancers marked with * use data from SEER 2012–2016 for 5-year survival as of 2016 (Howlader et al., 2020b); the stage of the disease was not reported for nervous system cancers or leukemia. PREPUBLICATION COPY—Uncorrected Proofs

66 DIAGNOSING AND TREATING ADULT CANCERS FINDINGS AND CONCLUSIONS Findings 1. The most common cancers diagnosed in the United States among both men and women are breast cancer, lung and bronchus cancer, prostate cancer, colon and rectum cancer, melanoma of the skin, bladder cancer, non-Hodgkin lymphoma, kidney and renal pelvis cancer, endometrial cancer, leukemia, pancreatic cancer, thyroid cancer, and liver cancer, a list that partially but not entirely paral- lels the common cancers listed in SSA disability claims. Among the reasons for the divergence is that cancer is primarily a disease of aging (median age at diagnosis for all cancers combined is 66 years), although about half of adults who develop cancer are of working age. 2. The incidence of cancer overall is increasing both because the population is aging and because cancer is being diagnosed more frequently among young adults; however, cancer mortality is de- clining as a result of improved detection and treatment. 3. Some cancers are more frequently diagnosed among younger adults, such as cancer of the testis, Hodgkin lymphoma, and acute lymphocytic leukemia. However, the incidence of some other can- cers (e.g., colorectal) are increasing in young people, potentially as a result of increasing obesity. 4. The incidence rates of lung and bronchus cancer and colorectal cancer have decreased in both adult men and adult women over the past 10 years, whereas the incidence of other cancers such as melanoma and, to a lesser extent, thyroid cancer has increased in both sexes. Breast cancer incidence has remained about the same over the last two decades. The trends reflect changes in screening, health behaviors, and public health approaches, such as tobacco control efforts. 5. Cancer incidence rates vary by race and ethnicity with Whites and Blacks having the highest cancer incidence rates overall and Asian/ Pacific Islanders and American Indian/Alaska Natives having the lowest incidence rates. 6. The cancers that result in the greatest mortality are not necessarily those with the greatest incidence (e.g., although breast cancer has an incidence rate more than twice that of lung cancer, its mortality rate is less than half that of lung cancer). 7. Cancer mortality rates have fallen since 1991, driven primarily by declines in mortality rates for the four leading cancers (breast, lung, PREPUBLICATION COPY—Uncorrected Proofs

CANCER EPIDEMIOLOGY 67 colorectal, and prostate). Cancer mortality is higher among men than women, and mortality rates increase with age. 8. In 2019 there were an estimated 16.9 million cancer survivors in the United States, of whom about one-third were younger than 65 years of age, and this number is expected to grow over the next two decades 9. Cancer-specific survival rates for many cancers have improved over the years, although there are often substantial differences in survival rates across cancer types which are explained in part by the disease stage at diagnosis. Survival rates tend to be better for cancers that are confined to the tissue of origin (i.e., localized disease), whereas cancers that are typically diagnosed at more ad- vanced stages tend to have poorer survival rates. 10. There are limited nationally representative data about the incidence and prevalence of impairments that result from cancer and its treatment. Conclusions 1. The population of cancer survivors is growing and will continue to do so as a result of earlier diagnosis of some cancers and advances in treatments. 2. Cancer survivors are living longer with impairments and functional limitations that are a result of their cancer and its treatment. REFERENCES ACS (American Cancer Society). 2020a. Key statistics for basal and squamous cell skin cancers. https://www.cancer.org/cancer/basal-and-squamous-cell-skin-cancer/about/key- statistics.html#references (accessed 2020, July 27). ACS. 2020b. Key statistics for breast cancer in men. https://www.cancer.org/cancer/breast- cancer-in-men/about/key-statistics.html (accessed September 21, 2020). ALA (American Lung Association). 2020. Overall tobacco trends. https://www.lung.org/ research/trends-in-lung-disease/tobacco-trends-brief/overall-tobacco-trends (accessed Sep- tember 21, 2020). Alberg, A.J., M.V. Brock, J.G. Ford, J.M. Samet, and S.D. Spivack. 2013. Epidemiology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 143(5 Suppl):e1S–e29S. Araghi, M., I. Soerjomataram, M. Jenkins, J. Brierley, E. Morris, F. Bray, and M. Arnold. 2019. Global trends in colorectal cancer mortality: Projections to the year 2035. International Journal of Cancer 144(12):2992–3000. Bluethmann, S.M., A.B. Mariotto, and J.H. Rowland. 2016. Anticipating the “silver tsunami”: Prevalence trajectories and comorbidity burden among older cancer survivors in the United States. Cancer Epidemiology Biomarkers & Prevention 25(7):1029–1036. CDC (Centers for Disease Control and Prevention). 2020a. Cancer. https://www.cdc.gov/ chronicdisease/resources/publications/factsheets/cancer.htm (accessed April 28, 2020). PREPUBLICATION COPY—Uncorrected Proofs

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Diagnosing and Treating Adult Cancers and Associated Impairments Get This Book
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Cancer is the second leading cause of death among adults in the United States after heart disease. However, improvements in cancer treatment and earlier detection are leading to growing numbers of cancer survivors. As the number of cancer survivors grows, there is increased interest in how cancer and its treatments may affect a person's ability to work, whether the person has maintained employment throughout the treatment or is returning to work at a previous, current, or new place of employment. Cancer-related impairments and resulting functional limitations may or may not lead to disability as defined by the U.S. Social Security Administration (SSA), however, adults surviving cancer who are unable to work because of cancer-related impairments and functional limitations may apply for disability benefits from SSA.

At the request of SSA, Diagnosing and Treating Adult Cancers and Associated Impairments provides background information on breast cancer, lung cancer, and selected other cancers to assist SSA in its review of the listing of impairments for disability assessments. This report addresses several specific topics, including determining the latest standards of care as well as new technologies for understanding disease processes, treatment modalities, and the effect of cancer on a person's health and functioning, in order to inform SSA's evaluation of disability claims for adults with cancer.

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