3
The Medical and Psychological Concerns of Cancer Survivors After Treatment

The medical and psychological effects of cancer and its treatment have been recognized for many years, but it is only recently that survivorship is coming to be recognized as a distinct phase of the cancer trajectory. Findings from research studies that have tracked the health and well-being of individuals long after cancer treatment has ended have identified risks that both the survivors and their health care providers should recognize. Advances in knowledge of how to manage conditions that arise in the post-treatment period have led to the development of some guidelines for health care providers to follow. The survivorship period provides many opportunities to improve the health and quality of life of cancer survivors. This chapter begins with a general overview of the potential medical and psychological consequences of cancer and its treatment. Brief descriptions are then provided on the late effects associated with four cancer types (breast, prostate, colorectal, and Hodgkin’s disease) as well as information on the need for services to ameliorate them. Lifestyle issues of interest to cancer survivors are reviewed—smoking cessation, physical activity, nutrition and diet, healthy weight, and the use of complementary and alternative medicine. The chapter concludes with a review of the committee’s findings and recommendations.

OVERVIEW

The meaning of health and life itself can be altered following a diagnosis of cancer (Herold and Roetzheim, 1992; Muzzin et al., 1994; Vachon, 2001). Cancer survivors report ongoing struggles to achieve a balance in



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From Cancer Patient to Cancer Survivor: Lost in Transition 3 The Medical and Psychological Concerns of Cancer Survivors After Treatment The medical and psychological effects of cancer and its treatment have been recognized for many years, but it is only recently that survivorship is coming to be recognized as a distinct phase of the cancer trajectory. Findings from research studies that have tracked the health and well-being of individuals long after cancer treatment has ended have identified risks that both the survivors and their health care providers should recognize. Advances in knowledge of how to manage conditions that arise in the post-treatment period have led to the development of some guidelines for health care providers to follow. The survivorship period provides many opportunities to improve the health and quality of life of cancer survivors. This chapter begins with a general overview of the potential medical and psychological consequences of cancer and its treatment. Brief descriptions are then provided on the late effects associated with four cancer types (breast, prostate, colorectal, and Hodgkin’s disease) as well as information on the need for services to ameliorate them. Lifestyle issues of interest to cancer survivors are reviewed—smoking cessation, physical activity, nutrition and diet, healthy weight, and the use of complementary and alternative medicine. The chapter concludes with a review of the committee’s findings and recommendations. OVERVIEW The meaning of health and life itself can be altered following a diagnosis of cancer (Herold and Roetzheim, 1992; Muzzin et al., 1994; Vachon, 2001). Cancer survivors report ongoing struggles to achieve a balance in

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From Cancer Patient to Cancer Survivor: Lost in Transition their lives and a sense of wholeness and life purpose after a life-altering experience (Ferrell, 2004). Individuals may reappraise their lives following a diagnosis of cancer and search for a sense of control and meaning. Survivors of cancer, although free of the cancer for which they were treated, may be immobilized by fears of recurrence and have difficulties making life decisions, for example, proceeding with vocational plans or marriage. Existential and spiritual issues may also arise related to concerns about death and dying, having a new orientation to time and future, and changed values and goals. The survivorship experience is dynamic, changing over time, with particular moments of stress being transitions, such as the transition from treatment to long-term follow-up. Cancer survivors face these psychosocial concerns and worries about the physical effects of their treatment across the continuum of cancer care (Ganz, 2000). Cancer’s effects are not isolated to an individual. Instead, it has an impact on the entire family, and the needs of children, spouses, partners, and other loved ones all need to be considered. Family members routinely provide personal care and emotional support for the duration of the cancer experience. Financial concerns may also arise because family income, insurance status, and employment can all be profoundly affected by cancer (see Chapter 6). Caregivers and family members often require, but do not receive, the respite, health care, psychosocial, and financial assistance they need in meeting the many needs of cancer survivors in their lives. Quality of life (QOL) is a term used widely to describe an individual’s assessment of his or her own general well-being. There is no one agreed-on conceptual model or definition for health-related QOL, and investigators continue to work on developing ways to measure outcomes that matter to patients (Ganz, 2002a; Zebrack et al., 2003). Central to the concept of QOL, however, is the importance of capturing the perspective of the patient across multiple “domains” or areas of well-being. Standardized, self-administered questionnaires are generally used to assess symptoms and functioning in physical, psychological, social, and spiritual domains (Mandelblatt and Eisenberg, 1995; Cella, 1995; Dow et al., 1996; Montazeri et al., 1996; Ferrell et al., 1997a,b, 1998; Ferrans, 2005).1 An example of a conceptual model of QOL is shown in Figure 3-1. This chapter reviews what is known about these various dimensions of quality of life for cancer survivors. The recognition of these health effects of 1   Some QOL instruments are generic in nature and are used in general population studies (e.g., Medical Outcomes Study Short Form 36 or SF-36), while others have been developed specifically for use among cancer patients or survivors (e.g., Cancer Rehabilitation Evaluation System or CARES).

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From Cancer Patient to Cancer Survivor: Lost in Transition FIGURE 3-1 Quality of life: conceptual model. SOURCE: City of Hope Beckman Research Institute (2004). Reprinted with permission from Betty R. Ferrell, PhD, FAAN; and Marcia Grant, DNSc, FAAN, City of Hope National Medical Center. cancer and its treatment, sometimes referred to as “the price of survival,” follows investments in cancer survivorship research directed to better understand the long-term consequences of cancer (Ganz, 2002b). Because most of the research conducted to assess QOL of cancer issues among survivors involves individuals with certain types of cancer (or certain treatments), descriptions of the cancer survivorship experience are provided by selected cancer site. What follows are brief reviews of the quality of life literature for individuals with a history of cancer of the breast, prostate, and colon and rectum, and Hodgkin’s disease. The terms “late effects” and “long-term effects” can be used to distinguish health effects according to their onset (Box 3-1). However, in this report, the general term “late effects” is used to describe the consequences of cancer and its treatment, regardless of their date of onset. There is limited information on the prevalence of late effects, but there is a general recognition that they have become more common, largely as a result of the more frequent use of complex cancer interventions,

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From Cancer Patient to Cancer Survivor: Lost in Transition BOX 3-1 Defining Late- and Long-Term Effects of Cancer Treatment Late effects refer specifically to unrecognized toxicities that are absent or subclinical at the end of therapy and become manifest later with the unmasking of hitherto unseen injury because of any of the following factors: developmental processes, the failure of compensatory mechanisms with the passage of time, or organ senescence. Long-term effects refer to any side effects or complications of treatment for which a cancer patient must compensate; also know as persistent effects, they begin during treatment and continue beyond the end of treatment. Late effects, in contrast, appear months to years after the completion of treatment. SOURCE: Aziz and Rowland (2003). often combinations of surgery, chemotherapy, radiation, and hormone treatments. Of particular concern for cancer survivors are psychological effects. There may be cancer-specific concerns, such as fear of recurrence, to more generalized symptoms of worry, fear of the future, fear of death, trouble sleeping, fatigue, and trouble concentrating (Box 3-2). The pervasive uncertainty associated with cancer survival has been labeled the “Damocles syndrome” (Smith and Lesko, 1988; Quigley, 1989; Herold and Roetzheim, 1992). In Greek mythology, Damocles was invited to the king’s banquet for dinner. Once there, he found himself seated beneath a sword suspended over his head by a single horsehair. Damocles was happy to be at the king’s feast, but any movement he made while reaching for food or drink might knock the sword loose and spell a quick death. For cancer survivors, fears of recurrence can result in persistent anxiety and difficulties in planning for the future (Lee-Jones et al., 1997). Individuals with cancer may also experience a mental disorder as a result of cancer or treatment, or they may experience an exacerbation of a prior psychiatric disorder (e.g., recurrent depression). Major depression and depressive symptoms occur frequently in cancer patients (Massie, 2004). According to a recent review of the literature, prevalence rates varied from 10 to 25 percent for major depressive disorders, a rate at least four times higher than in the general population (AHRQ, 2002). The timing and method of the assessment, concurrent treatment, medical morbidity, pain, gender, and age of subjects contributed to the wide range of estimates. The higher rates are usually seen in patients with more advanced illness and uncontrolled pain or other physical symptoms. The term “psychosocial distress” has been coined to reflect a broader

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From Cancer Patient to Cancer Survivor: Lost in Transition BOX 3-2 Psychosocial Concerns of Cancer Survivors Negative Fear of recurrence, concerns about future and death Depression, sadness Inability to make plans Adjustment to physical compromise, health worries, sense of loss for what might have been (e.g., loss of fertility) Uncertainty and heightened sense of vulnerability Alterations in social support Fears regarding accomplishment of adult developmental tasks Existential and spiritual issues Psychosocial reorientation Sexuality, fertility, and intimate relationships Parenting Employment and insurance problems Relationship with the treatment team Positive Feelings of gratitude and good fortune Sense of self-esteem and mastery SOURCE: Ganz (2002c). set of concerns (NCCN, 1999). As conceived, distress is a “multi-factorial unpleasant emotional experience of a psychological (cognitive, behavioral, emotional), social, and/or spiritual nature that may interfere with the ability to cope effectively with cancer, its physical symptoms, and its treatment. Distress extends along a continuum, ranging from common normal feelings of vulnerability, sadness, and fears to problems that can become disabling, such as depression, anxiety, panic, social isolation, and existential and spiritual crisis” (NCCN, 1999). Distress may be experienced as a reaction to the disease and its treatment and also as a result of the consequences of the disease on employment, health insurance, and social functioning, including family relationships (McEvoy and McCorkle, 1990; Kornblith, 1998) (see Chapter 6 for a discussion of employment and insurance issues). Brief screening tools can be used to identify individuals with symptoms of distress so that clinical assessment by the primary oncology team and referral to psychosocial providers can take place (Trask, 2004). The Distress Thermometer, for example, is a visual analogue scale that the National Comprehensive Cancer Network (NCCN) guidelines suggest for the screening of psychosocial distress (NCCN, 1999). Many survivors function at high levels and do not report excess depres-

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From Cancer Patient to Cancer Survivor: Lost in Transition sive symptoms. Importantly, not all of the psychological effects are negative. Cancer survivors are often grateful to be alive and have an enhanced appreciation of life. Their self-esteem and sense of mastery may also be enhanced. Social late effects may be negative (alienation and isolation) or positive (affinity and altruism). Socioeconomic concerns may arise following treatment, particularly financial concerns related to costs of care, access to health insurance, and the ability to return to work or school (see Chapter 6). Recent evidence suggests that there are income-related disparities in the QOL of cancer survivors that cannot be explained by the effect of health on earnings. High-income patients are not only more likely to survive cancer, but they enjoy better QOL as survivors (Short and Mallonee, in press). Aside from psychosocial distress, there are two main categories of late effects. First, cancer survivors are at increased risk for cancer, either a recurrence of the cancer for which they were initially treated, or the independent development of a second cancer (either of the same type or a different type from the original cancer).2 The increased risk of developing a second cancer may be due to cancer treatment (e.g., chemotherapy-induced leukemia and bladder cancer), genetic or other susceptibility, or some interaction between treatment and an inherent susceptibility. In addition to concerns about the risk of cancer following treatment, cancer survivors are at increased risk for a wide range of treatment-related problems notable for their variability and unpredictability. Their variability can be traced, in part, to the complexity of cancer itself (e.g., the type of tumor and stage of disease), the wide array of therapies that can be employed, the intensity of treatment (e.g., doses of chemotherapy or radiation, the extent of surgery needed), and the age and underlying health status of the individual at the time of treatment. A number of tissues and body systems can potentially be impaired as a consequence of cancer and its treatment, as illustrated in Tables 3-1 and 3-2. Some of the late effects associated with certain chemotherapeutic agents, for example, can result in significant changes in physical functioning, leading to effects such as post-treatment fatigue or sexual or urinary problems. Clinicians, in designing initial treatment plans, consider the potential for late effects and attempt to be as conservative as guidelines warrant to maximize treatment effectiveness while minimizing late effects. Late effects will likely be reduced in the future with the advent of therapies that are tailored to the characteristics of an individual and their cancer. In addition, advances in methods to assess individuals risk for late effects (e.g., their DNA repair mechanisms related to radiation-induced DNA damage) and to personalize treatments will improve the outlook for cancer survivors. 2   A National Cancer Institute (NCI) monograph on the risks of second cancers is forthcoming by early 2006.

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From Cancer Patient to Cancer Survivor: Lost in Transition TABLE 3-1 Examples of Possible Late Effects of Radiation Therapy, Chemotherapy, and Hormonal Therapy Among Survivors of Adult Cancers Organ System/Tissue Radiation Therapy Late Effects Chemotherapy/Hormonal Therapy Late Effects Agent Responsible All tissues Second cancers Second cancers Steroids, alkylating agents, nitrosureas, topoisomerase inhibitors, anthracyclines Bone and soft tissue Atrophy, deformity, fibrosis, bone death Bone death and destruction, risk of fractures Steroids Cardiovascular Scarring or inflammation of the heart, coronary artery disease; scarring of heart sac (pericardium) Inflammation of the heart, congestive heart failure Anthracylines, high-dose cyclophosphamide, cisplatin, herceptin, taxanes Dental/oral health Dental caries, dry mouth — — Endocrine-pituitary Various hormone deficiencies Diabetes Steroids Endocrine-thyroid Low thyroid function, thyroid nodules — — Endocrine-gonadal Men: Sterility, testosterone deficiency Women: Sterility, premature menopause Men: Sterility, testosterone deficiency Women: Sterility, premature nitrosureas Alkylating agents, Procarbazine hydrochloride, menopause Gastrointestinal Malabsorption, intestinal stricture Motility disorders Vinca drugs Genitourinary Bladder scarring, small bladder capacity Hemorrhagic cystitis (symptoms include urinary frequency, urgency, bleeding, and pain) Cyclophosphamide, ifosfamide, transplant therapy

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From Cancer Patient to Cancer Survivor: Lost in Transition Hematologic Low blood counts, myelodysplastic syndrome and acute leukemia Myelodysplastic syndrome and acute leukemia Alkylating agents, nitrosureas, topoisomerase inhibitors, purine analogs, any high-dose therapy with autologous transplantation Hepatic Abnormal liver function, liver failure Abnormal liver function, cirrhosis, liver failure Methotrexate, carmustine (BCNU) Immune system Impaired immune function, immune suppression Impaired immune function, immune suppression Steroids, anti-thymocyte globulin (ATG), methotrexate, rituximab, alemtuzumab, purine analogs, and any high-dose therapy with autologous transplantation Lymphatic Lymphedema — — Nervous system Problems with thinking, learning, memory; structural changes in the brain; bleeding into the brain Problems with thinking, learning, memory; structural changes in the brain; paralysis; seizure Methotrexate, multiagent chemotherapy, bortezomib     Numbness and tingling, hearing loss Cisplatin     Numbness and tingling Vinca alkaloids, taxanes. oxaliplatin Ophthalmologic Cataracts, dry eyes, visual impairment Cataracts Steroids Pulmonary Lung scarring, decreased lung function Lung scarring, inflammation Bleomycin sulfate, carmustine (BCNU), methotrexate     Potentiation of radiation therapy effects (gemcitabine) Actinomycin D/doxorubicin (Adriamycin) Renal Hypertension, impaired kidney function Impaired kidney function, delayed-onset renal failure Cisplatin, methotrexate, nitrosoureas

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From Cancer Patient to Cancer Survivor: Lost in Transition TABLE 3-2 Examples of Possible Late Effects of Surgery Among Survivors of Adult Cancers Procedure Late Effect Any procedure Pain, cosmetic, psychosocial, impaired wound healing Surgery involving neurologic structures (brain, spinal cord) Impairment of cognitive function, motor sensory function, vision, swallowing, language, bowel and bladder control Head and neck surgery Difficulties with communication, swallowing, and breathing; cosmetic; damage to muscles affecting movement Removal of lymph nodes Lymphedema, retrograde ejaculation in testicular cancer Abdominal surgery Risk of intestinal obstruction, hernia, altered bowel function Pelvic surgery Sexual dysfunction, incontinence, hernia, risk of intestinal obstruction Removal of spleen Impaired immune function, increased risk of sepsis, hernia Amputation; limb-sparing procedures Functional changes; cosmetic deformity; psychosocial impact; accelerated arthritis in other joints; post-surgical, phantom, and/or neuropathic pain Lung resection Difficulty breathing, fatigue, generalized weakness Prostatectomy Urinary incontinence, sexual dysfunction, poor body image Oophorectomy Premature menopause and infertility Orchiectomy Infertility, testosterone deficiency Ostomy Bowel obstruction, constipation, nausea, vomiting, loss of appetite, fatigue, poor body image Second cancers are perhaps the most frequent life-threatening late effect, but other disabling conditions may occur. Some of these are identified early in follow-up and resolve without consequence (e.g., treatment-related fatigue). Other late effects may persist, become chronic problems, and influence the progression of other diseases associated with aging (e.g., radiation-induced changes in the lung called “radiation pneumonitis,” renal failure). Some late effects may only become evident years after treatment (e.g., congestive heart failure, graft versus host disease, neurological syndromes). Certain late effects are easy to identify because they are visible or have direct effects on function. Examples include major paralysis from brain or spine neoplasms, communication and swallowing problems from head and neck cancers, and limb loss or deformity due to osteosarcoma or another

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From Cancer Patient to Cancer Survivor: Lost in Transition type of sarcoma. Many affected individuals, in addition to their medical surveillance needs, require expensive equipment, such as wheelchairs or prostheses, to maintain functional independence and quality of life. Such equipment requires maintenance and often replacement over the lifespan. Other effects, however, can be subtle and apparent only to the trained observer (e.g., change in posture secondary to osteoporosis) or are not directly observable and identified only through diagnostic tests (e.g., for hypothyroidism, infertility). It is sometimes difficult to distinguish among cancer-related changes, age-related changes, and those caused by comorbid conditions (see Chapter 2 for a description of the survivor population by age and comorbidity). Cancer can be considered a chronic disease, in part because of the serious consequences and persistent nature of some of cancer’s late effects. The limited empirical evidence on the late effects of adult cancer treatment is primarily confined to small case series that are not population-based. There are relatively few longitudinal cohort studies available to understand the link between specific treatment regimens and late physical and psychological effects, making it difficult to describe the natural history of late effects for patients and their health care providers. Unfortunately, absent data from longitudinal studies, the degree of risk of late effects to individual patients cannot be predicted. To illustrate the range of late effects and the diversity of the cancer survivor population, one could consider the individual who had an early-stage melanoma successfully removed, leaving an inconspicuous scar, to have had cancer with minimum late effects and impact on life. Such a person would have concerns regarding subsequent risk of cancer, but likely would not suffer serious long-term health effects of treatment. At the other extreme might be an individual with a hematological cancer undergoing intensive chemotherapy followed by a bone marrow transplant. Such a person would face substantial long-term health problems associated with treatment. This variation in survivorship experience is more fully described in the next section, where late effects and interventions to ameliorate them are more fully described for four cancer types: cancer of the breast, prostate, and colon and rectum, and Hodgkin’s disease. These sites were selected because more than half of all cancer survivors have had these types of cancer. In addition, they were selected because investigators have focused research on these cancers and there is an extensive survivorship literature available. Other cancer sites, while not covered at length in this review, also have potential for major, varied, and often lifelong disabling effects. For example, individuals with brain or spine tumors may develop severe neurologic deficits (Mukand et al., 2001); survivors of head and neck cancer may have impaired eating, communication, and musculoskeletal functions of the neck and shoulder (Hammerlid and Taft, 2001); and individuals with bone

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From Cancer Patient to Cancer Survivor: Lost in Transition cancers may require amputations or limb-sparing procedures that interfere with mobility (Hoffman et al., 2002). SITE-SPECIFIC REVIEW The following brief site-specific summaries of late effects of cancer and its treatment are based on selected reviews and literature to which the reader is referred for more detailed information. Information on interventions that are available to ameliorate these health effects are also described, as are available clinical practice guidelines (CPGs) for the management of late effects. CPGs are “systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances” (IOM, 1990). Female Breast Cancer3 The experience of survivors of breast cancer has been the most extensively researched. Women with a history of breast cancer are the largest group of cancer survivors, representing 22 percent of the survivorship population (see Chapter 2 for a description of breast cancer survivors). The evolving nature of breast cancer treatment has generated a heterogeneous group of breast cancer survivors (Box 3-3). Elderly survivors treated 20 to 30 years ago, for example, had fewer treatment options and likely experienced mastectomy. The issues of concern to those women were often linked to late effects of surgery such as lymphedema and body image. Younger cohorts of women, in contrast, have benefited from a wider range of options, but may be concerned about a broader set of late effects related to their treatment. Quality of Life At the conclusion of primary treatment for breast cancer, women generally report good emotional functioning, but decreased physical function- 3   Much of this section is based on recent comprehensive reviews relating to breast cancer treatment and late effects (Burstein and Winer, 2000; Shapiro and Recht, 2001; Partridge et al., 2001, 2003; Emens and Davidson, 2003; Hurria and Hudis, 2003; Kattlove and Winn, 2003; Harris et al., 2004; Mrozek and Shapiro, 2005). Literature was identified by searching PubMed for articles published in English since 1994 with the MeSH heading “breast neoplasms” and an additional search term, including “survivors” [MeSH], “lymphedema” [MeSH], “menopause” [MeSH], “heart diseases” [MeSH], “weight gain,” “cognitive impairment,” “fatigue,” and “late effects.” Articles relating to childhood cancer survivors were excluded.

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