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Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
Correspondence: Richard T. Penson, M.R.C.P., M.D., Instructor in Medicine, Hematology-Oncology, Cox 548, 100 Blossom Street, Boston, Massachusetts 02114-2617, USA. Telephone: 617-726-5867; Fax: 617-724-6898; e-mail: rpenson{at}partners.org
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LEARNING OBJECTIVES
Top
Learning Objectives
Abstract
Case Presentation
Dialogue
Discussion
Conclusion
References
After completing this course, the reader will be able to:
| ABSTRACT |
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Ageism is a pervasive problem throughout society. It is rooted in language, attitudes, beliefs, behaviors, and policies. Aging profoundly influences physiology, challenging the medical community to accommodate but not discriminate. The elderly are at an increased risk of disease and disability. Sixty percent of cancer occurs in people aged 65 and older, and the population is aging. The treatment of cancer in the elderly is complicated by comorbidities and other physiological factors, particularly renal, bone marrow, and metabolic reserve. Caregivers have to treat patients in a manner that optimizes treatment and avoids anticipated harm. However, the caregiver is often faced with situations where they must balance their personal beliefs, professional values, and knowledge of medicine with their patients preferences and needs. Discussion in the Rounds focused on age bias, drug toxicity, life prolongation, and symptom relief, with the role of the caregiver, and the relationship to the patient, being pivotal.
Key Words. Oncology • Support • Psychosocial • Communication • Chemotherapy • Connection • Elderly • Age
| CASE PRESENTATION |
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At age 70, Mrs. L was diagnosed with head and neck cancer. She successfully underwent surgery and radiation, which she tolerated well. More than a decade later, she was diagnosed with bladder cancer. She received radiation and again did well on therapy. The treatment approach to the small cell lung carcinoma was complicated by her weakened condition, and it was initially unclear how aggressively to treat the cancer.
| Caregivers often assume that life-prolonging therapy is more important to younger patients, whereas symptom relief is more important to elderly patients.
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The small cell lung carcinoma was limited to the chest, with no evidence of metastasis. The standard therapy for this type of lung cancer involves an intensive combination of radiation and chemotherapy. She wanted to be treated aggressively. She received two cycles of full-dose carboplatin and etoposide chemotherapy, which she tolerated well. During the third cycle, the dose was reduced, and she began radiation therapy just as she was released from the rehabilitation hospital. Once at home, Mrs. L found it difficult to get to the hospital for daily radiation therapy, and received only 7 of the 25 scheduled fractions. Although Mrs. L had periodic visiting nurse support, she appeared unwell, disheveled, and in need of basic daily living care by the end of radiation therapy.
Four weeks later, Mrs. L returned to the hospital for a follow-up computerized tomography (CT) scan of her chest. She had gained weight, was walking with a cane, and looked remarkably vibrant and healthy. Her cough, chest pain, and shortness of breath had all disappeared. The CT scan revealed a complete response to the radiation and chemotherapy treatments, and there was essentially no sign of remaining disease. She was encouraged to finish radiation therapy, but declined because she was finally feeling strong and healthy. She felt that she couldnt go through any more therapy without being hospitalized, which she adamantly did not want to do. The therapy had been extremely hard on her and all she wanted to do was to enjoy her life and feel good again.
| DIALOGUE |
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Physician: I have to agree with the oncologists initial impression of Mrs. L. I knew that Mrs. L was undergoing postsurgical rehabilitation for her hip and wrist at Spaulding Rehabilitation Hospital and that she was coming to Massachusetts General Hospital for treatment of her lung cancer. However, once I saw this frail elderly woman rolling into the hospital in a wheelchair with a brace on her left arm, I thought, "How can we do this? How is she going to tolerate this therapy?" I am always willing to try different therapeutic regimens with my patients, but I had qualms about trying any therapy with her. Mrs. L, on the other hand, had no reservations whatsoever about trying therapy.
In the past, Mrs. Ls husband had made her refuse chemotherapy for her two previous cancers. It is interesting that she was making her treatment decisions this time. Because she was at Spaulding, I think it was easier for her to finally make an autonomous decision about her care. Her husband was not there to steer her in the direction that he felt was best, and she was competent and confident about her decision to be treated. Any reservations that I had when I first saw her disappeared the moment she said, "Im doing this."
Social Worker: The theme that stands out the most about this case is our inherent age bias. As a society, we think about age as a disease. Age is not a disease.
| There are so many reasons for life- prolonging therapy, but we simply dont take the time to find out about these reasons.
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Physician: I think the first question that should be addressed is, "Do we make assumptions about our elderly patients solely based on age?" Unfortunately, I feel that the answer to this question is "yes." However, these assumptions are not always negative or necessarily discriminatory. There is a significant biological basis to that bias. The kidneys of a healthy 35-year old certainly function differently than the kidneys of a healthy 70-year old. The older we get, the tougher it is to tolerate most treatments. In general, older patients are more likely to have, and not tolerate, complications from treatment as compared to younger patients. They are also less likely to recover from these complications. The fact that a patient is elderly must factor into our assessments, judgments, and decisions about treatment.
Facilitator: The problem is that it isnt easy to escape our biases. No matter how much we want to believe that we see people for who they are, the truth is that age does play a significant role in how we perceive people. We need to be able to determine when age should play a role in our decisions, and when age is tainting our view of the person beneath the wrinkles. When is it appropriate clinical acumen and when is it ageism?
Physician: Another important theme involves the issues of life prolongation and symptom relief. When I first met Mrs. L, I felt that we couldnt put her through an intensive treatment regimen. The most that I was considering was minimal chemotherapy for palliation or hospice care. However, Mrs. L clearly wanted aggressive treatment in order to extend her life.
Oncologist: This case certainly reveals our misconceptions about our elderly patients. We often assume that our elderly patients have lived long, fulfilling lives; therefore, it is not our job to prolong their lives as much as make the rest of their lives more comfortable. That is not to say that we abandon our expectations of ultimately curing the patient, but we are more concerned about an elderly patients immediate health than about the future. We are protective of our elderly patients because they are less resilient to intensive treatment and chronologically much closer to death. We seem to view symptom relief, but not life-prolonging therapy, as essential to the elderly. We may wonder why an 84-year old with a long medical history wants to live longer, but we should not be overly surprised that this person, who happens to be elderly, actually wants to live a longer life.
Facilitator: There are so many reasons for life- prolonging therapy, but we simply dont take the time to find out about these reasons. In Mrs. Ls case, it appears that she was the sole caregiver to her husband, who was not a particularly well man himself. Although they had children, the children did not appear to play a role in their lives. Mrs. L wasnt interested in prolonging her life so that she could run in the next Boston marathon; she simply wanted to be around to care for her husband.
Physician: She also understood that aggressive treatment could be extremely toxic to her system, with the possibility that the toxicities would cause her death. She was definitive about trying the therapy and fully understood the dangers, but felt that it was worth the risk.
Oncologist: It should not be surprising that Mrs. L wanted aggressive, and potentially life-prolonging, therapy. Elderly patients are more willing to take risks than we think. It is important for us to provide our elderly patients with reasonable treatment options and biological-based explanations. However, we also need to understand their thoughts about those treatment options and respect their wishes. We cant always offer them a cure, but in some cases, we can offer them treatment regimens typically reserved for younger, healthier patients. Although these regimens may not seem overly realistic, we need to consider why an elderly person wants to live longer, and treat them accordingly.
Facilitator: This has been an excellent discussion. I think it is important that we have begun this dialogue. We need to become more aware of our intrinsic age bias while exercising, and balancing, sound clinical judgment. We need to continue exploring these issues as we treat our elderly patients.
| DISCUSSION |
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| Cancer is an indiscriminate disease that can affect any human being. One in three people will get cancer in their lifetime.
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In the next 25 years, the elderly population (
65 years of age) is expected to increase to 20% of the total population of the U.S., up from 13% in 2000 [3, 4]. As the elderly population increases, the incidence of cancer in the elderly is also expected to increase [5]. Aging is a complex and highly individualized process, reflecting chronologic, as well as physiologic, age [6, 7]. Chronologic age, by itself, does not accurately mirror the aging process. True aging reflects physiologic changes in the body that affect function and form. Although aging is common to everyone, aging affects individuals differently and at different paces.
Physiological Foundation of Aging
Aging is a highly individualized, multidimensional process that is associated with changes in the genetics, biochemistry, physiology, and anatomy of the body. As the body ages, deterioration occurs in functional, emotional, socioeconomic, and cognitive areas [810]. Functional status is a benchmark of overall health and independence [11, 12]. Aging directly correlates with declining functional status and increased functional dependency. Aging is also associated with the increased likelihood of developing concurrent diseases, called comorbidities [1316], and diseases which are typically linked to aging, known as "geriatric syndromes" [1721]. Comorbidities complicate the overall health of the elderly and significantly increase with advancing age [22]. On average, people aged 65 and older report three different, concurrent diseases [23, 24]. The most common comorbid diseases are depression, arthritis, and cardiovascular disease. Both functional dependence and comorbidity are associated with a shorter life expectancy [15, 2527].
Cancer: Acute Aging
Many molecular mechanisms emphasize the association between aging and cancer [28]. The carcinogenic process involves genetic and epigenetic abnormalities to cells resulting in altered cell functions. The age-related incidence of malignancy reflects the complexity of the carcinogenic steps that are required in their development [28]. Cancers are thought to arise through a stepwise accumulation of mutations that favor uncontrolled cell growth, prevent apoptosis, recruit a blood supply, avoid the immune system, and spread or metastasize [29, 30].
Cancer is thought to be inherent to long-lived organisms, since they need to use continuous cell growth for the development and maintenance of tissues and organs. Proliferating cells are more prone to DNA damage and the acquisition of genetic instability than quiescent cells. This can result in the occurrence of mutations that promote uncontrolled cell proliferation. In order to achieve immortalization, such cells need to circumvent two failsafe mechanisms, replicative senescence (cell aging) and cellular crisis, that are controlled by telomere shortening and the p53 and Rb tumor-suppressor pathways. Telomeres are nucleoprotein structures that cap chromosome ends and play an important role in preventing chromosomal erosion. In most normal cells, telomeres shorten with each cell division [31]. Ultimately, this "mitotic clock" leads to cell senescence when telomere length reaches a certain size [32]. Activation of the p53 and Rb tumor-suppressor pathways plays an important role in cell senescence and, subsequently, the elimination of cells with eroded, unstable chromosomes. Unstable chromosomes are prone to chromosomal degradation, rearrangements, aberrant fusion, and genetic instability, which are perpetuated by the loss of the p53 and Rb tumor-suppressor genes. Additionally, cancers can circumvent telomere shortening and senescence by constitutively activating telomerase, a specialized reverse transcriptase enzyme that maintains and extends the telomeric ends [33]. Most human cells have low telomerase activities and, thus, limited replication potentials.
Recent research in mice points to another connection between cancer and aging. Mice engineered to upregulate activity of the p53 tumor-suppressor gene have a lower incidence of cancer development [34, 35]. However, this comes at the price of premature aging and death. Thus, it appears that the same mechanisms that protect us from cancer also contribute to aging. Tissue microenvironment also plays an important role in the manifestation of cancer physiology [36]. Autopsies of individuals who died from trauma often reveal microscopic cancerous lesions. However, the incidence of cancer among individuals of the same age is significantly lower, suggesting that the majority of people carry microscopic lesions that do not manifest themselves as clinically recognizable cancer [37]. Folkman and Kalluri attribute this phenomenon to the bodys intrinsic capacity to prevent growth of microscopic tumors through the control of angiogenesis and the activation of immune defenses [38]. It is possible that age-associated decline in overall health creates a microenvironment that fails to suppress cancer growth.
| Ageism is rooted in language, attitudes, beliefs, behaviors, and policies.
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Healthy cellular and organism functions reflect a tension between cell proliferation and cell senescence. Investigation of the paradox that cellular aging is also the trigger for the common cancer is likely to contribute significantly to our understanding of tumor biology. Cell aging and senescence may be the inherent defense mechanisms that prevent uncontrolled cell proliferation. When senescence fails, cancer prevails.
Ageism
Ageism is defined as "prejudice toward, stereotyping of, and/or discrimination against any person or persons directly and solely as a function of their having attained a chronological age which the social group defines as old" [39].
Ageist views are prevalent throughout history and throughout society. However, unlike other types of discrimination, ageism is more consistently expressed in a subtle manner. Rather than hearing slurs directed at the elderly on the street, ageist language is often present in friendly, everyday conversation. The use of language, such as "not looking our age" or having a "senior moment," perpetuates unbecoming and often inaccurate views of aging. Ageism is rooted in language, attitudes, beliefs, behaviors, and policies.
The ageism that permeates society also pervades clinical medicine. Despite frequent contact with the elderly, clinicians are often influenced by ageist views and deep-seated biases. As a result, the elderly are often undertreated [4042], or treated differently, for many common diseases without consideration for their physiologic, rather than their chronologic, age.
Age Bias
There is an inherent age bias throughout society. It involves the concepts of stereotyping, prejudice, and discrimination against the elderly population. Age bias ranges from individual disrespect to formal, institutionalized policies that discriminate against the elderly population. The elderly are often judged based on perceptions, preconceived notions, and deep-seated beliefs. Although the elderly population is an extremely heterogeneous group, there is an anonymous distance in portraying them uniformly. The dominant image in society depicts the elderly person as dependent, frail, and a burden on community resources [43], as well as sickly, unkempt, and incompetent. Regrettably, television portrayals of the elderly often reinforce these stereotypes of decline and incompetence [44, 45]. The process of aging, particularly in U.S. society, relegates the elderly person to a lower status within the social structure. Essentially, aging implies hierarchical decline. This is moderated in other cultures, where investigators report more positive views of aging and respect for the elderly [46, 47].
Age bias also exists in the clinical setting. Therefore, clinicians must balance their personal beliefs, professional values, and knowledge of medicine with their patients preferences and needs. The issues of undertreatment and overtreatment constantly challenge clinicians who treat cancer in the elderly. Undertreatment can compromise potentially curative therapy, while overtreatment risks unacceptable toxicity.
The elderly are more likely than younger patients to be treated with substandard therapy for cancer, which is only partially explained by the higher prevalence of comorbidities in the elderly population [48]. Physicians tend to undertreat elderly patients because of the perceived minimal benefit of chemotherapy or the risk of toxicity from standard chemotherapeutic regimens [48]. In a study of 1,449 patients with colorectal cancer, Ayanian et al. surveyed physicians and reviewed office records in order to assess the use of adjuvant chemotherapy and radiation therapy. It was found that the use of chemotherapy varied greatly by patient age. Chemotherapy was administered to 88% of the patients who were younger than age 55, while only 11% of the patients aged 85 or older received chemotherapy. Rates were similarly discrepant for the use of radiation therapy. Other factors that affected the use of adjuvant therapy included race, marital status, hospital volume, and individual hospital [40].
Similarly, a breast cancer study examined the recommendation for the use of adjuvant chemotherapy among chemotherapy-eligible patients aged 50 or older. The results demonstrated that increasing age was strongly associated with a lower likelihood of receiving a recommendation for chemotherapy treatment. In total, 74% of the 208 chemotherapy-eligible patients were recommended for chemotherapy. Chemotherapy was recommended to 92% of the women aged 5059, 77% of the women aged 6069, and 23% of the women aged 7079. The odds of receiving a favorable recommendation for chemotherapy decreased by 22% per year [49].
A questionnaire-based study of diagnostic and case-mix factors was carried out on 1,652 lung cancer patients in the United Kingdom in order to examine treatment management and 6-month survival rates. The results showed large age-related differences in the management and survival of patients, largely independent of case-mix factors. Patients were divided into three age groups: under 65 years, 6574 years, and 75 years and older, and surgical resection rates were assessed. It was found that 37% of the patients under 65 years of age underwent surgical resection compared with only 15% of the patients aged 75 years and older. Not surprisingly, the younger patients had significantly superior survival [42].
| The elderly are more likely than younger patients to be treated with substandard therapy for cancer, which is only partially explained by the higher prevalence of comorbidities in the elderly population.
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Age [5052], socioeconomic status [53], and the caregivers personal values have been found to affect the way in which caregivers communicate with, impart information to [54], and treat their patients [5557]. Further evidence suggests that caregivers personal opinions and preferences, as well as their nonprofessional values, influence, if not determine, their professional behavior [58].
Functional Status, Comorbidity, and Toxicity
The treatment of cancer in the elderly population is further complicated by physiological factors, including functional status, physiologic compromise, and limited tolerance of treatment. There is no equation to guide tailoring the optimal therapeutic regimen. The oncologist must weigh the patients prior medical history with his/her current overall health and functional status and the presence or absence of comorbidities. The oncologist is then forced to make judgments about the most suitable treatment plan based on standard chemotherapeutic regimens. Standard chemotherapeutic regimens, however, are primarily based on clinical trials that do not include elderly patients. Caregivers are reluctant to enter elderly cancer patients into clinical trials because of the general lack of knowledge concerning their treatment tolerance and response. It is possible that age bias also affects caregivers attitudes toward the use of elderly patients in clinical trials. In a survey of U.S. oncologists, 51% indicated that they excluded patients solely on the basis of age [59]. Yet, when offered participation in clinical trials, both younger and older patients accepted the opportunity at similar rates. Thus, it appears that the exclusion of elderly patients from clinical trials is predominantly physician, rather than patient, driven [60].
While chronologic age is not considered a contraindication to full-dose chemotherapy, elderly cancer patients with poor functional statuses and comorbid diseases are at a considerably increased risk of ineffective treatment, and potentially fatal toxicity [61]. It is not at all clear which independent risk factors best predict drug toxicity. While there are often limited data, etoposide, for example, has shown a correlation between age and toxicity [62]. Age is an important predictor of metabolic capacity [63], although perhaps not as powerful as major gender differences in metabolism or functional polymorphisms, as is seen with 5-fluorouracil [64]. It has been shown that decreases in p450 activity, protein binding, creatinine clearance, and bone marrow reserves as well as greater fat-to-muscle ratios, are all factors that contribute to drug toxicity in aged patients. Optimizing the use of chemotherapeutic drugs in elderly cancer patients is a challenge [65, 66].
Life Prolongation and Symptom Relief
Just as aging is a highly individualized process [6, 7], the decisions concerning treatment plans and the ultimate goals of chemotherapy are also personal and distinctive. It is clear that the burden of treatment, the likelihood of beneficial treatment outcomes, and the consequences of toxicity are decisive factors in patients preferences for specific therapeutic regimens [6777]. Fried et al. examined the treatment preferences of seriously ill patients who had limited life expectancies due to cancer, congestive heart failure, or chronic obstructive pulmonary disease [78]. A questionnaire was administered to 226 patients aged 60 or older describing low-burden and high-burden treatment approaches and the expected outcomes. The low-burden approach involved minor tests, simple therapies, and a maximum hospital stay of 1 week, while the high-burden approach involved more complex tests and therapies and a minimum hospital stay of 1 month. The expected outcomes consisted of three scenarios: a return to current health; severe functional impairment wherein the patient required assistance with all daily activities; and severe cognitive impairment in which the patient was unaware of his/her surroundings. When the treatment burden was high but the outcome was a return to current health, 88.8% of the patients wanted treatment. However, when the treatment burden was low but the outcome was severe functional impairment or severe cognitive impairment, only 25.6% and 11.2%, respectively, wanted treatment.
| Clinicians must learn how to balance their personal and professional beliefs with the needs and preferences of their patients in order to provide their patients with optimum care.
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The majority of the literature suggests that elderly cancer patients do favor symptom relief over life prolongation. In a study by Somogyi-Zalud et al., hospitalized patients aged 80 and older were asked to assess their preferences for life-extending measures or comfort care [79]. Seventy percent of the patients reported that they desired comfort care over life-extending measures. Similarly, in a study of end-of-life treatment preferences among older adults, Resnick and Andrews found that the majority of older adults did not want life-sustaining or life-prolonging treatments [80]. Yellen et al. found that elderly cancer patients were as likely as younger cancer patients to desire aggressive chemotherapy for both curative and palliative purposes, but were less willing to exchange toxicity for life prolongation. [81]. These studies support previous research that indicates that the majority of older adults prefer treatments that facilitate comfort over those that prolong life [82]. Symptom relief is clearly a highly valued treatment outcome for elderly patients [83]. Unfortunately, research continues to report that very old hospitalized patients, who subsequently died while hospitalized, often received life-sustaining treatments regardless of their desire for comfort care [79], despite the widely accepted tenet that "the provision of care at the end of life should honor patients preferences" [78].
Collusion: The Unspoken Agreement
Collusion is a secret agreement or cooperation especially for a deceitful or illegal purpose [84]. In this case, collusion involves the spoken and unspoken interactions between caregiver and patient that enable them to avoid sensitive subjects and promote a false sense of hope for the patient. The caregiver and patient may both be equally tempted to unrealistically deny the issues and overtreat, or fatalistically limit treatment.
The et al. describe a variety of collusive actions that occur at different stages throughout the course of small cell lung cancer [85]. Such actions include the concealment of prognosis, emphasis on treatment to the exclusion of other important issues, use of ambiguous language, and adherence to the "recovery plot." These allow the caregiver to impart hope, while the patient feels empowered that they are actively combating their disease.
Collusion can take on many forms, but its ultimate goal is to avoid addressing painful issues and inevitable outcomes. Caregivers and patients actively participate in collusion, which is mutually beneficial because "the physician does and does not want to pronounce a death sentence, and the patient does and does not want to hear it" [85].
Addressing Ageism in Medicine
Programs that target the relationships between students and the elderly population are increasingly becoming a part of medical education. These new and innovative approaches are intended to bridge the gap and foster understanding between the young and the old. The key component to these approaches involves direct contact between a student and an elderly mentor, with the intention of developing this contact into a meaningful, symbiotic relationship.
The University of Missouri-Kansas City School of Medicine has paired first- and second-year medical students with healthy elderly mentors. The program, which lasts 2 years, involves the students interacting and completing projects with their mentor, as well as keeping personal journals and writing scholarly papers. Thus far, the students have learned important lessons, experienced improved communication, and developed strong bonds with their mentors [86].
Similarly, a community health care project, called the Council of Elders, was developed to provide a voice to the elderly population and learn from the patient as teacher. The group of elders consisted of four women and men ranging in age from 78100 years. They were responsible for listening to medical dilemmas involving the elderly that young clinicians encountered during their primary-care residency training. The elders were asked to discuss the dilemmas and provide their thoughts and opinions about the cases. During the course of the program, many of the young clinicians realized that their perceptions of the elderly were inaccurate, and they became acutely aware of their own stereotypes. Subsequently, this experience positively affected the clinicians practices [87].
| CONCLUSION |
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The treatment of cancer in the elderly population is riddled with stereotypes, prejudice, and discrimination. Clinicians must learn how to balance their personal and professional beliefs with the needs and preferences of their patients in order to provide their patients with optimum care. Clinicians do not want to be responsible for exposing elders to unacceptably toxic treatment, and yet, there is a pervasive limitation of treatment that compromises the care of the elderly. What is clear is that "the elderly should not be denied adequate treatment simply on the basis of age alone" [88].
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