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Suggested Citation:"1 Introduction." 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:"1 Introduction." 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:"1 Introduction." 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:"1 Introduction." 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:"1 Introduction." 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:"1 Introduction." 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:"1 Introduction." 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:"1 Introduction." 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:"1 Introduction." 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:"1 Introduction." 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:"1 Introduction." 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:"1 Introduction." 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:"1 Introduction." 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:"1 Introduction." 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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1 Introduction A cancer diagnosis and its treatment can affect the lives of people who have or have had cancer (that is, cancer survivors) in many ways, often over long periods of time. Fortunately, recent progress in cancer research has yielded new knowledge about cancer biology and resulted in a number of innovative treatments for people who have cancer. This report is an overview of the current status of the diagnosis, treatment, and prognosis of select common adult cancers, particularly breast cancer and lung cancer, and their effects on the health and functioning of people with cancer. Cancer is a group of diseases characterized by uncontrolled growth in which the body’s cells divide without stopping and spread into surrounding tissues, often forming solid masses known as tumors (NCI, 2016). It is the second leading cause of death in the United States after heart disease (CDC, 2020a), and it was estimated that in 2020 more than 1.8 million new cases of cancer were diagnosed and more than 600,000 deaths occurred from it (Siegel et al., 2020).1 Cancer is a major public health problem: the lifetime probability for developing cancer in the United States is about 40% in males and about 39% for females (Siegel et al., 2020). The cancer diagnosis and treatment landscape has changed dramati- cally in the past two decades, reflecting basic science discoveries in genetics 1  The committee notes that this estimate was made before the coronavirus disease 2019 (COVID-19) pandemic began in early 2020 in the United States. In the United Kingdom it has been estimated that there may be approximately 5–17% additional deaths from breast, lung, esophageal, and colorectal cancers over the next 5 years as a result of delayed diagnosis due to COVID-19 (Maringe et al., 2020). 17 PREPUBLICATION COPY—Uncorrected Proofs

18 DIAGNOSING AND TREATING ADULT CANCERS and immunology that occurred at the beginning of this century (e.g., the Human Genome Project). These discoveries have transformed scientific understanding of cancer biology and resulted in new diagnostic and treat- ment strategies that are now in regular clinical use. During the past century, cancer treatment planning focused almost solely on the anatomic extent of cancer, best characterized by a staging system that quantifies tumor size, as well as the extent of regional and distant spread. Now pathologists iden- tify the unique expression of a tumor’s genetic and immune features on an initial biopsy so that this information can be incorporated with traditional diagnostic approaches to chart a personalized treatment plan for the pa- tient. These changes are exemplified by the contemporary management of breast cancer and lung cancer but are also seen across a broad range of other cancers, several of which are also discussed briefly in this report. There is considerable excitement about these new and emerging treatments (e.g., targeted therapies, immunotherapy). However, much less is known about the long-term and late-onset effects of these treatments compared with the conventional approaches to surgery, chemotherapy, and radiation that have been used for more than 50 years. While cancer remains a major cause of mortality in the United States, improvements in cancer treatment and survival are leading to increasing numbers of cancer survivors. While the definition of “cancer survivors” has sometimes varied, this term generally includes anyone with a history of cancer and is used from the time of diagnosis until death (see Box 1-1). BOX 1-1 Who Is a Cancer Survivor? A cancer survivor “is any person with a history of cancer, from the time of diagnosis through the remainder of their life.” This population includes those who are: • “Living cancer-free after treatment for the remainder of life • Living cancer-free after treatment for many years but experiencing one or more serious, late complications of treatment • Living cancer-free after treatment for many years, but dying after a late recurrence • Living cancer-free after the first cancer is treated, but developing a sec- ond cancer • Living with intermittent periods of active disease requiring treatment • Living with cancer continuously, with or without treatment, without a disease-free period.” SOURCE: ACS, 2016. PREPUBLICATION COPY—Uncorrected Proofs

INTRODUCTION 19 Although all individuals diagnosed with cancer can be considered cancer survivors, in this report the committee also uses the term “cancer patients” to describe cancer survivors who are engaged in active cancer treatment. Cancer death rates have decreased every year during the past 20 years, for an overall drop of 26% between 1999 and 2018 (CDC, 2020b). There are currently 17 million cancer survivors (Miller et al., 2019), and this num- ber is expected to grow to 26 million by 2040 (Bluethmann et al., 2016). More than one-third of cancer survivors are between 20 and 64 years of age (Miller et al., 2019). Survival rates have improved significantly, with the 5-year survival rate for all cancers increasing from 50% in 1981–1983 to 69% in 2005–2008 (NCI, 2019a). During this period, there was an even larger increase in the 5-year survival rate for some specific cancers, such as leukemia, which improved from 37% to 62% (NCI, 2019a). In 2019, 67% of survivors (10.3 million) had survived 5 years or more after diagnosis; 45% had survived 10 years or more; and 18% had survived 20 years or more (ACS, 2019) (see Table 1-1). To help address the needs of the growing population of child and adult cancer survivors, in 1996 the National Cancer Institute (NCI) established the Office of Cancer Survivorship (NCI, 2020). The mission of the office is to support further study and to fund research focused on the physical and emotional challenges faced by cancer survivors in the years after their initial diagnosis and treatment. Research funded by NCI and other organizations has highlighted the ongoing morbidities experienced by many cancer sur- vivors, with concomitant declines in both physical and mental health, as well as the challenges they face in taking part in normal activities, including TABLE 1-1 Estimated Number of U.S. Cancer Survivors by Sex and Years Since Diagnosis Male and Female Male Female Years Since Diagnosis Number % Number % Number % 0 to <5 years 5,527,420 33 2,921,800 36 2,605,620 30 5 to <10 years 3,802,050 23 1,957,220 24 1,844,830 21 10 to <15 years 2,684,620 16 1,323,430 16 1,361,190 16 15 to <20 years 1,855,780 11 843,970 10 1,011,810 12 20 to <25 years 1,198,320 7 491,980 6 706,340 8 25 to <30 years 773,770 5 290,450 4 483,320 6 30+ years 1,078,430 6 309,960 4 768,470 9 SOURCES: Adapted from ACS (2019) with permission. Based on data from Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, as of January 1, 2019. PREPUBLICATION COPY—Uncorrected Proofs

20 DIAGNOSING AND TREATING ADULT CANCERS work. Regardless of the time since diagnosis, cancer survivors report poorer health and more comorbidities than people who have never had cancer (Yabroff et al., 2004). Cancer-related impairments and functional limitations can be caused by the cancer itself (e.g., compromised breathing from a tumor’s direct inva- sion of the lungs or difficulty walking because of a brain tumor), or they may be caused by cancer treatments such as surgery, radiation therapy, and systemic therapy, or they may be due to a combination of both the cancer and its treatment. Cancer treatment–related impairments include those that may develop during treatment but resolve when the treatment or healing is complete (acute effects), such as postoperative pain, as well as those that develop during treatment and become chronic (long-term effects), such as chronic neuropathy following chemotherapy, persistent fatigue, or lymph- edema. Some impairments such as radiation fibrosis syndrome, may not be evident during treatment but may develop weeks, months, or even years after the cancer treatment is complete (late-onset effects). In turn, these late-onset impairments may result in secondary impairments such as fatigue which may also limit a person’s functioning (NASEM, 2020a). 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. Return to work is a particularly important and salient issue since the me- dian age for a cancer diagnosis in the United States is 66 years (SEER, n.d.) and thus approximately half of all newly diagnosed cancer patients are of working age (de Boer et al., 2009; Short et al., 2005). In a meta-analysis de Boer et al. (2009) found that the relative risk of receiving a disability benefit or otherwise being disabled for work was almost three times higher for can- cer survivors than for individuals without a history of cancer. The improved survival rates that have resulted from new and emerging treatments mean that cancer survivors are living longer but may also experience long-term and late-onset impairments from those treatments for a longer period of time. In turn, longer periods of impairment may have consequences for can- cer survivors’ ability to work because of such factors as their increased need for workplace accommodations, occupational supportive care throughout treatment, and disability benefits for a longer time than previously expected (Kiasuwa Mbengi et al., 2016). The most common cancers in terms of the numbers of estimated new cases diagnosed in 2020 are listed in Box 1-2 (see Chapter 3 for more in- formation on number of cases by cancer and sex). While all of these cancers and their treatments have the potential to cause disability, some cancers and treatments are more likely to cause disability than others, depending on the cancer site, cancer stage, and severity and duration of treatment as well as PREPUBLICATION COPY—Uncorrected Proofs

INTRODUCTION 21 BOX 1-2 Common Adult Cancers Diagnosed in the United States in 2020 • Breast cancer • Lung and bronchus cancer • Prostate cancer • Colorectal cancer • Melanoma of the skin • Bladder cancer • Non-Hodgkin lymphoma • Kidney and renal pelvis cancer • Uterine cancer • Leukemia SOURCE: SEER, n.d. other clinical factors, including comorbidities. For example, Horsboel et al. (2014) found that patients with hematological cancers have an increased risk of requiring disability than patients who have other cancers, possibly as a result of treatment with intensive chemotherapy and bone marrow transplants. A cancer survivor’s ability to remain employed may also be influenced by sociodemographic factors including personal factors (age, education, sex, or race) and work-related/social factors (employment type and physical demands, company size, or amount of social support) (Endo et al., 2020). de Boer et al. (2009) found that cancer survivors were more likely to be un- employed than individuals without cancer (33.8% compared with 15.2%), particularly survivors of breast cancer, gastrointestinal cancers, and cancers of the female reproductive organs. The negative effects of long-term unem- ployment include a decreased quality of life and lower self-esteem as well as a level of financial distress that can cause other detrimental effects (Beesley et al., 2018; van der Noordt et al., 2014; Verbeek et al., 2003; Zagozd- zon et al., 2014). To help alleviate financial concerns, cancer patients and survivors who are unable to work because of cancer-related impairments have the option to apply for disability benefits from the U.S. Social Security Administration (SSA). When cancer patients and survivors apply for disability benefits, SSA is required by the Social Security Act to determine their eligibility and, if they are approved, provide them monetary benefits (see Chapter 2). The 1990 Americans with Disabilities Act2 (ADA) prohibits discrimination based on certain disabilities in the workplace and requires employers 2  Americans with Disabilities Act of 1990, 42 U.S.C. Chapter 126 § 12101 (1990). PREPUBLICATION COPY—Uncorrected Proofs

22 DIAGNOSING AND TREATING ADULT CANCERS to provide reasonable accommodations for individuals with disabilities in order for them to perform their job duties. While both of these laws were enacted to help disabled individuals, they have differing purposes and eligibility requirements. For example, receiving disability benefits from SSA is based on one’s inability to work, perform basic job duties, or engage in any other kind of substantial gainful activity; thus, SSA disability benefits provide the necessary support to people who can no longer work as a result of their health. Conversely, the ADA protections benefit individuals who can still perform essential parts of their jobs but may need reasonable accommodations from their employers—such as providing a reasonable amount of additional unpaid leave for medical treatment, making existing facilities usable by disabled employees, or allowing a flexible work schedule—to do so3 (Greidanus et al., 2018; Williams-Whitt et al., 2016). Research has shown that employers can play an essential role in promoting the work participation of cancer survivors, with supervisor support being an important return-to-work facilitator. In order to make the correct disability decisions, SSA dis- ability programs need to reflect current medicine as well as the evolution of work. A more detailed discussion of the SSA disability determination process can be found in Chapter 2. COMMITTEE’S CHARGE In order to keep the information on which it bases its disability list- ings as current as possible, in 2019 SSA asked the National Academies of Sciences, Engineering, and Medicine (the National Academies) to convene a committee of experts to provide an overview of the diagnosis, treatment, and prognosis of selected adult cancers, particularly breast cancer and lung cancer (see Box 1-3 for the committee’s complete Statement of Task). This report is intended to provide SSA with background information on breast cancer, lung cancer, and selected other cancers to assist in its review of the listing of impairments for disability assessments. SSA asked the National Academies study committee to address several specific topics, including determining the latest standards of care as well as new technologies for understanding disease processes, treatment modali- ties, 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. The study committee was asked to not examine access to care for diagnosing and treating cancer, and it was not asked to make recommendations based on its overview of the current status of cancer diagnosis, treatment, or prognosis. 3  SSR 00-1c (Jan 7, 2000). PREPUBLICATION COPY—Uncorrected Proofs

INTRODUCTION 23 BOX 1-3 Statement of Task An ad hoc committee of the National Academies of Sciences, Engineering, and Medicine will conduct a study to provide an overview of the current status of the diagnosis, treatment, and prognosis of select common adult cancers. In developing its report the committee will: 1. Provide an overview of the current status of the diagnosis, treatment, and prognosis of adult cancers including, but not limited to, breast cancer and lung cancer, and the relative levels of associated functional limitation typically associated with these cancers, common treatments, and other considerations in the U.S. population age 18 and older; 2. Identify adult cancers with recent advances in treatment or changes in prognosis, including but not limited to breast cancer, and lung cancer, and describe to the degree possible: a. The professionally accepted diagnostic techniques used in identifying adult cancers (for example, laboratory and clinical findings); b. The stages of adult cancers, how the stages are determined (for ex- ample, by specific laboratory findings), and what the stages mean in terms of treatment and prognosis; c. Clinical standards for identifying complete remission or cure, and variability in the time period used to identify remission, the difference between complete remission and partial remission (if appropriate), and the consequences of partial remission (for example, if partial remission results in a reduction in type or intensity of treatment); d. Secondary impairments that result from either the cancer or the treatment (for example, cognitive impairment following certain treatment); and e. Common long-term and late effects of the cancer or therapy. 3. Identify the types of treatments available and describe to the degree possible: a. The clinical practice guidelines for receiving the treatments; b. The settings in which the treatments are provided; c. What receipt of the treatments indicates about the severity of the medical condition; and d. The likelihood of improvement when receiving the treatments and the period over which the improvement would be expected; 4. Provide a summary of selected treatments currently being studied in clini- cal trials for adult cancers; and 5. Provide the median survival time and survival rates dependent on the stage and the type of cancer (including area of body affected). The report will include conclusions but not recommendations. The committee shall not describe issues with respect to access to treatments. While the U.S. So- cial Security Administration (SSA) recognizes people may have difficulty accessing care or particular forms of treatment, some do successfully access those treat- ments. SSA may receive information about those treatments in the medical records SSA considers when making disability determinations and conducting continuing disability reviews. SSA understands improvement is not certain in all cases. SSA makes individual decisions on each case based on all the evidence they receive. PREPUBLICATION COPY—Uncorrected Proofs

24 DIAGNOSING AND TREATING ADULT CANCERS COMMITTEE’S APPROACH To accomplish the Statement of Task, the National Academies empan- eled a committee of 15 members with expertise in the areas of the diagnosis and treatment of breast cancer, lung cancer, hematopoietic cancers, and colorectal cancer; radiation oncology; cancer survivorship and rehabilita- tion; long-term and late-onset effects of cancer and its treatment; cognitive impairment; primary care; mental health; and epidemiology (see Appendix A for the biographical sketches of the committee members). The committee held five meetings which included two public sessions. At the first public session SSA provided more specifics on its objectives for the study, and the committee heard from a researcher studying the impact of cancer on employment and productivity. At the second public session the committee heard from four cancer survivorship advocates and held a panel discussion to explore more fully the impact of cancer and its treatment on long-term impairments, functional limitations, and quality of life during and after cancer treatment (see Appendix B for the public session agendas). In addition, the committee conducted an extensive review of the litera- ture pertaining to the selected cancers in adults, including literature specific to cancer diagnosis, treatment, and functional outcomes. Committee mem- bers and project staff identified additional literature and information using traditional academic research methods and online searches throughout the course of the study. The committee’s work was further informed by previous National Academies’ reports related to disability and to cancer, which are referenced throughout the report. In addition, the National Academies recently com- pleted a study for SSA on childhood cancers and disability that reviewed the status of the diagnosis, treatment, and prognosis of common select child- hood cancers, in the U.S. population under 18 years of age and identified the relative levels of functional limitation typically associated with the can- cers, their common treatments, and other considerations (NASEM, 2020b). POPULATION OF INTEREST AND SELECTION OF CANCERS Cancer survivors between the ages of 18 and 65 years are an impor- tant population for SSA because these working-age adults have complex responsibilities, including family caregiving, as well as educational ac- tivities, employment pressures, and financial needs. These individuals may also experience certain challenges related to cancer and its treatment more frequently than those younger than 18 years or older than 65 years. For example, adults who have cancer at a younger age are likely to have higher rates of cancer-related pain (Lundstedt et al., 2012; Macdonald et al., 2005; Schou Bredal et al., 2014), lower quality of life (Champion et al., 2014; PREPUBLICATION COPY—Uncorrected Proofs

INTRODUCTION 25 Green et al., 2011; Kroenke et al., 2010), and higher levels of financial hardship (Banegas et al., 2016; Guy et al., 2014; Yabroff et al., 2016) than those who have cancer at older ages. The highest incidence rates of cancer in working-age adults are for breast, colorectal, lung, melanoma of the skin, lymphoma, and leukemia (based on age-adjusted incidence SEER data, 2012–2016; see Chapter 3). Innovations in new cancer treatments and standards of care, most notably in breast and lung cancer, may substantially affect the long-term outcomes in these adult survivors. SSA asked the National Academies committee to focus on breast cancer and lung cancer, but it also asked that the committee consider other can- cers for which changes in incidence, diagnosis, treatment, or prognosis are occurring. Thus, the committee addressed those cancers most prevalent in SSA’s disability claims (for more information on SSA disability claims, see Chapter 2). For example, although prostate cancer is the third most com- mon cancer diagnosed in the United States in 2020 (an estimated 191,930 new cases), it is not among the most common cancers listed in SSA disabil- ity claims, nor is it frequently diagnosed in men under the age of 65 (NCI, 2019b; Siegel et al., 2020); therefore, it is not discussed in this report. Although SSA provides benefits for children with cancer who are dis- abled, these children are not considered in this report as SSA assesses their disabilities differently than it does for adults who have cancer. The com- mittee recognizes that adult survivors of pediatric cancers may experience long-term impairments and subsequent functional limitations, including the development of new cancers. The committee considers these new cancers in the same manner as cancers that develop in adults. Pediatric cancers and their associated impairments are examined in the 2020 National Academies report Childhood Cancer and Functional Impacts Across the Care Con- tinuum (NASEM, 2020b). ORGANIZATION OF THE REPORT Providing an overview of the current status of the diagnosis, treat- ment, and prognosis of breast, lung, and other selected adult cancers was a complex task. New technologies and an improving understanding of the biology of cancer are resulting in rapid advances in both the diagnosis and the treatment of these cancers, which in turn are affecting the long-term outcomes for cancer survivors. To address these issues, the committee began by requesting information from SSA on what cancers are most frequently encountered in the disability claims it receives. SSA’s process for determin- ing disability and the detailed information it provided on the cancers it most frequently reviews are presented in Chapter 2. However, SSA’s most common cancers do not necessarily parallel those seen in the general U.S. PREPUBLICATION COPY—Uncorrected Proofs

26 DIAGNOSING AND TREATING ADULT CANCERS population. Chapter 3 compared the epidemiology of SSA’s most common cancers with the U.S. population’s most common cancers. The chapter provides information on the incidence of new cases, mortality rates, and survival from the cancers most common in SSA disability claims. An over- view of the diagnosis and treatment of adult cancers, with an emphasis on current standards of care as recommended in clinical practice guidelines, is given in Chapter 4. This chapter also discusses the screening for and stag- ing of cancer as well as cancer prognosis. Chapters 5 and 6 build on the standards of care in Chapter 4 and apply them to breast cancer and lung cancer, respectively. There are four major subtypes of breast cancer and two major subtypes of lung cancer. Differences in the staging, diagnosis, treat- ment, and prognosis of the several subtypes are described, and the implica- tions for the long-term outcomes for survivors of these cancers are assessed. Treatments for these cancers include surgery, radiation, and systemic treat- ments, and their use for each cancer and subtype is explained. To address SSA’s request that the committee also consider other cancers as appropriate, Chapter 7 highlights new information on the incidence and treatment of several cancers frequently seen in SSA disability claims, including gastro- intestinal cancers (colorectal, pancreatic, and liver and bile duct cancers), hematologic cancers (leukemias, lymphomas [Hodgkin and non-Hodgkin], and myelomas), ovarian cancer, head and neck squamous cell cancers, and melanoma of the skin. The committee included the last cancer because it is a commonly diagnosed cancer in the U.S. population (see Box 1-2) and new advances in treatment have greatly improved its prognosis, which may affect future SSA disability claims. Chapter 8 provides an overview of the many new and emerging therapies that are being tested in clinical trials. The committee distinguishes between new treatments—those already ap- proved by the U.S. Food and Drug Administration for some cancers, and now being explored as potential treatments for other cancers—and emerg- ing treatments, or those that are not yet approved but are in clinical trials to determine their effectiveness and safety. Although the committee focuses on pharmaceutical agents in this chapter, it also considers new approaches for surgery and radiation therapies. The various treatments discussed in chapters 4 through 8 all have some level of deleterious effects on cancer survivors as does cancer itself. The long-term and late-onset adverse effects of cancer and its treatments (impairments) are assessed in Chapter 9. While some treatments may have few lasting effects, others such as radiation, che- motherapy, and targeted therapy agents can have prolonged impacts on a survivor’s functioning which may not resolve for months or years or which may last a lifetime. Cancer-related impairments may affect both physical and mental health, and their prevalence, diagnosis, treatment, and progno- sis are considered in this chapter. Chapter 10 looks at the future of cancer PREPUBLICATION COPY—Uncorrected Proofs

INTRODUCTION 27 survivorship and what can be done by cancer survivors, caretakers, health care professionals, and organizations to ensure that the survivors receive the care necessary for their optimal functioning after their diagnosis. The concept of cancer survivorship is becoming more widely acknowledged, and more people are recognizing that a diagnosis of cancer is no longer a death sentence, even though the effects of cancer and its treatment may be evident for years. Finally, Appendix A presents short biographical sketches of the committee members, and Appendix B contains the agendas for the committee’s public sessions. REFERENCES ACS (American Cancer Society). 2016. Cancer treatment & survivorship facts & figures 2016–2017. Atlanta, GA: American Cancer Society. ACS. 2019. Cancer treatment & survivorship facts & figures 2019–2021. Atlanta, GA: American Cancer Society. Banegas, M.P., G.P. Guy, J.S. de Moor, D.U. Ekwueme, K.S. Virgo, E.E. Kent, S. Nutt, Z. Zheng, R. Rechis, and K.R. Yabroff. 2016. For working-age cancer survivors, medical debt and bankruptcy create financial hardships. Health Affairs 35(1):54–61. Beesley, V.L., C. Alemayehu, and P.M. Webb. 2018. A systematic literature review of the preva- lence of and risk factors for supportive care needs among women with gynaecological cancer and their caregivers. Support Care Cancer 26(3):701–710. Bluethmann, S. M., A. B. Mariotto, and J. H. Rowland. 2016. Anticipating the “silver tsu- nami”: Prevalence trajectories and comorbidity burden among older cancer survivors in the United States. Cancer Epidemiol 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 January 15, 2020). CDC. 2020b. An update on cancer deaths in the United States. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Division of Cancer Prevention and Control. Champion, V.L., L.I. Wagner, P.O. Monahan, J. Daggy, L. Smith, A. Cohee, K.W. Ziner, J.E. Haase, K.D. Miller, K. Pradhan, F.W. Unverzagt, D. Cella, B. Ansari, and G.W. Sledge, Jr. 2014. Comparison of younger and older breast cancer survivors and age-matched controls on specific and overall quality of life domains. Cancer 120(15):2237–2246. de Boer, A.G., T. Taskila, A. Ojajarvi, F.J. van Dijk, and J.H. Verbeek. 2009. Cancer survivors and unemployment: A meta-analysis and meta-regression. JAMA 301(7):753–762. Endo, M., G. Muto, Y. Imai, K. Mitsui, K. Nishimura, and K. Hayashi. 2020. Predictors of post-cancer diagnosis resignation among Japanese cancer survivors. Journal of Cancer Survivorship 14(2):106–113. Green, C.R., T. Hart-Johnson, and D.R. Loeffler. 2011. Cancer-related chronic pain. Cancer 117(9):1994–2003. Greidanus, M.A., A.G.E.M. de Boer, A.E. de Rijk, C.M. Tiedtke, B. Dierckx de Casterlé, M.H.W. Frings-Dresen, and S.J. Tamminga. 2018. Perceived employer-related barriers and facilitators for work participation of cancer survivors: A systematic review of em- ployers’ and survivors’ perspectives. Psycho-Oncology 27(3):725–733. Guy, G.P., Jr., K.R. Yabroff, D.U. Ekwueme, A.W. Smith, E.C. Dowling, R. Rechis, S. Nutt, and L.C. Richardson. 2014. Estimating the health and economic burden of cancer among those diagnosed as adolescents and young adults. Health Affairs 33(6):1024–1031. PREPUBLICATION COPY—Uncorrected Proofs

28 DIAGNOSING AND TREATING ADULT CANCERS Horsboel, T.A., C.V. Nielsen, N.T. Andersen, B. Nielsen, and A. de Thurah. 2014. Risk of dis- ability pension for patients diagnosed with haematological malignancies: A register-based cohort study. Acta Oncologica 53(6):724–734. Kiasuwa Mbengi, R., R. Otter, K. Mortelmans, M. Arbyn, H. Van Oyen, C. Bouland, and C. de Brouwer. 2016. Barriers and opportunities for return-to-work of cancer survivors: Time for action—rapid review and expert consultation. Systematic Reviews 5(1):35. Kroenke, K., D. Theobald, J. Wu, J.K. Loza, J.S. Carpenter, and W. Tu. 2010. The association of depression and pain with health-related quality of life, disability, and health care use in cancer patients. Journal of Pain and Symptom Management 40(3):327–341. Lundstedt, D., M. Gustafsson, G. Steineck, P. Malmström, D. Alsadius, A. Sundberg, U. Wilderäng, E. Holmberg, K.-A. Johansson, and P. Karlsson. 2012. Risk factors of devel- oping long-lasting breast pain after breast cancer radiotherapy. International Journal of Radiation Oncology, Biology, Physics 83(1):71–78. Macdonald, L., J. Bruce, N.W. Scott, W.C.S. Smith, and W.A. Chambers. 2005. Long-term follow-up of breast cancer survivors with post-mastectomy pain syndrome. British Jour- nal of Cancer 92(2):225–230. Maringe, C., J. Spicer, M. Morris, A. Purushotham, E. Nolte, R. Sullivan, B. Rachet, and A. Aggarwal. 2020. The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: A national, population-based, modelling study. The Lancet Oncology 21:1023–1034. Miller, K.D., L. Nogueira, A.B. Mariotto, J.H. Rowland, K.R. Yabroff, C.M. Alfano, A. Jemal, J.L. Kramer, and R.L. Siegel. 2019. Cancer treatment and survivorship statistics, 2019. CA: A Cancer Journal for Clinicians 69(5):363–385. NASEM (National Academies of Sciences, Engineering, and Medicine). 2020a. Selected health conditions and likelihood of improvement with treatment. Washington, DC: The Na- tional Academies Press. NASEM. 2020b. Childhood cancer and functional impacts across the care continuum. Wash- ington, DC: The National Academies Press. NCI (National Cancer Institute). 2016. What is cancer? https://www.cancer.gov/about-cancer/ understanding/what-is-cancer (accessed January 15, 2020). NCI. 2019a. Relative survival rates by year of diagnosis. In SEER cancer statistics re- view, 1975–2016. https://seer.cancer.gov/archive/csr/1975_2016/results_merged/topic_ survival_by_year_dx.pdf (accessed August 31, 2020). NCI. 2019b. SEER cancer statistics review, 1975–2016. https://seer.cancer.gov/archive/ csr/1975_2016 (accessed April 29, 2020). NCI. 2020. About cancer survivorship. https://cancercontrol.cancer.gov/ocs/about/index.html (accessed August 18, 2020). Schou Bredal, I., N.A. Smeby, S. Ottesen, T. Warncke, and E. Schlichting. 2014. Chronic pain in breast cancer survivors: Comparison of psychosocial, surgical, and medical characteristics between survivors with and without pain. Journal of Pain and Symptom Management 48(5):852–862. SEER (Surveillance, Epidemiology, and End Results). n.d. Cancer stat facts: Cancer of any site. https://seer.cancer.gov/statfacts/html/all.html (accessed September 3, 2020). Short, P.F., J.J. Vasey, and K. Tunceli. 2005. Employment pathways in a large cohort of adult cancer survivors. Cancer 103(6):1292–1301. Siegel, R.L., K.D. Miller, and A. Jemal. 2020. Cancer statistics, 2020. CA: A Cancer Journal for Clinicians 70(1):7–30. van der Noordt, M., H. IJzelenberg, M. Droomers, and K.I. Proper. 2014. Health effects of employment: A systematic review of prospective studies. Occupational and Environmen- tal Medicine 71(10):730–736. PREPUBLICATION COPY—Uncorrected Proofs

INTRODUCTION 29 Verbeek, J., E. Spelten, M. Kammeijer, and M. Sprangers. 2003. Return to work of cancer survivors: A prospective cohort study into the quality of rehabilitation by occupational physicians. Occupational and Environmental Medicine 60(5):352–357. Williams-Whitt, K., U. Bültmann, B. Amick, F. Munir, T.H. Tveito, J.R. Anema, B.C. Amick, J.R. Anema, E. Besen, P. Blanck, C.R.L. Boot, U. Bültmann, C.C.H. Chan, G.L. Delclos, K. Ekberg, M.G. Ehrhart, J.-B. Fassier, M. Feuerstein, D. Gimeno, V.L. Kristman, S.J. Linton, C.J. Main, F. Munir, M.K. Nicholas, G. Pransky, W.S. Shaw, M.J. Sullivan, L.E. Tetrick, T.H. Tveito, E. Viikari-Juntura, K. Williams-Whitt, A.E. Young, and the Hopkin- ton Conference Working Group on Workplace Disability. 2016. Workplace interventions to prevent disability from both the scientific and practice perspectives: A comparison of scientific literature, grey literature and stakeholder observations. Journal of Occupational Rehabilitation 26(4):417–433. Yabroff, K.R., W.F. Lawrence, S. Clauser, W.W. Davis, and M.L. Brown. 2004. Burden of ill- ness in cancer survivors: Findings from a population-based national sample. Journal of the National Cancer Institute 96(17):1322–1330. Yabroff, K.R., E.C. Dowling, G.P. Guy, Jr., M.P. Banegas, A. Davidoff, X. Han, K.S. Virgo, T.S. McNeel, N. Chawla, D. Blanch-Hartigan, E.E. Kent, C. Li, J.L. Rodriguez, J.S. de Moor, Z. Zheng, A. Jemal, and D.U. Ekwueme. 2016. Financial hardship associated with cancer in the United States: Findings from a population-based sample of adult cancer survivors. Journal of Clinical Oncology 34(3):259–267. Zagozdzon, P., J. Parszuto, M. Wrotkowska, and D. Dydjow-Bendek. 2014. Effect of un- employment on cardiovascular risk factors and mental health. Occupational Medicine 64(6):436–441. PREPUBLICATION COPY—Uncorrected Proofs

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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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