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Version of Record online: 3 DEC 2008
Copyright © 2008 American Cancer Society
Supplement: Cancer and Aging: Challenges and Opportunities across the Cancer Control Continuum
Volume 113, Issue Supplement 12, pages 3505–3511, 15 December 2008
How to Cite
Given, B. and Given, C. W. (2008), Older adults and cancer treatment. Cancer, 113: 3505–3511. doi: 10.1002/cncr.23939
Sponsored by the National Cancer Institute's Office of Cancer Survivorship.
Presented at the Society of Behavioral Medicine preconference entitled, “Cancer and Aging: Challenges and Opportunities across the Cancer Control Continuum,” Washington, DC, March 21, 2007.
- Issue online: 3 DEC 2008
- Version of Record online: 3 DEC 2008
- Manuscript Accepted: 13 MAY 2008
- Manuscript Revised: 24 APR 2008
- Manuscript Received: 7 NOV 2007
- Family Home Care for Cancer—A Community-Based Model
- National Cancer Institute. Grant Number: R01 CA079280
- Automated Telephone Monitoring for Symptom Management
- National Cancer Institute. Grant Number: R01 CA030724
- cancer treatment;
- older adults;
- behavioral research;
- physical function;
- side effects
Approximately 60% of cancer incidence occurs in adults aged ≥65 years, yet older patients often are not accorded access to treatment trials. Therefore, providers remain uninformed about clinical and behavioral responses of older patients with cancer to cancer treatment. The objectives of this article were to provide a broad overview of some of the dimensions of cancer treatment in the elderly and to raise issues for behavioral research. The literature was reviewed in general for cancer treatment and specifically to address areas such as comorbidity, function, adverse events, palliation, side effects, social and psychological factors, cognition, and provider behavior. The authors address the importance of behavioral research and discuss issues for behavioral researchers in the context of cancer treatment. Few studies were identified that were specific to behavioral research. The results indicated that chronological age alone is an inadequate indicator to determine responses among older patients to cancer treatment. When they are selected carefully, older patients can benefit from treatment or palliation. More research is needed to define clinical and behavioral criteria for the inclusion of older patients in treatment trials. Cancer 2008;113:(12 suppl) 3505–11. © 2008 American Cancer Society.
Individuals aged 65 years can expect to live another 15 years and remain functionally independent. Individuals ages 75 to 84 years have an average longevity of 10 years, whereas individuals aged 85 years have an average longevity of 6 years.1 Approximately 60% of cancer incidence and 70% of cancer mortality occur among adults aged ≥65 years. Currently, 6 million cancer survivors aged >65 years have undergone cancer treatment. Historically, to exclude patients who had multiple comorbid conditions, few randomized chemotherapy trials enrolled patients older than aged 65 years.2, 3 Although age alone is no longer an exclusion criteria, little evidence exists describing how psychosocial and behavioral factors influence decisions regarding whether to treat, the course of treatment, or the outcomes of care for older adults with cancer. Older cancer patients are physiologically, psychologically, socially, economically, and culturally heterogeneous. Consequently, there is a complexity in the care of older cancer patients that deserves to be addressed through research on this growing segment of the population.2 Balducci and Beghe,4 Muss et al,5 Extermann,6 Repetto,7 and Rodin and Mohide,8 have emphasized the critical importance of applying the principles of geriatric oncology in the management of older adults with cancer. Decisions regarding the treatment and management of cancer need to consider how comorbid conditions, functional status, and cognitive status are related to tolerance and benefit from treatment among this population as scientists begin to unravel the science of cancer and aging.9, 10
The objective of this report was is to summarize the psychosocial literature on the treatment and care of older adults with cancer. It is important to emphasize that the focus of this article is not on chronological age but on the importance of the interplay among the biologic, psychological, and social factors of aging among older cancer patients. We recognize that selecting appropriate treatment protocols for older individuals with cancer can be challenging and involve a review of therapies and how they may interact with comorbid conditions, organ deterioration, or geriatric syndromes and how they may affect physical and cognitive status. The interplay of these clinical factors may be complicated by the availability of family support to maintain the patient at home and to provide transportation necessary for access to care. We examine how psychosocial research, broadly defined, can inform treatment approaches to older patients with cancer. We argue that, before selecting a treatment plan for the older patient, a more comprehensive screening and evaluation should be undertaken. To this end, we have summarized the dimensions to be evaluated and the state of the science related to these assessments.
SCREENING AND EARLY DETECTION FOR THE OLDER CANCER PATIENT
Cancer screening guidelines for older adults are not clear. General frameworks for making decisions regarding screening exist11; however, for breast cancer, they appear to be left to the discretion of providers or patients.12 For prostate cancer, the rates of screening among the elderly with limited life expectancy may be too high.13, 14 After a cancer diagnosis, elderly patients should be evaluated carefully regarding how comorbidity, physical function, and psychosocial health may influence treatment plans.
Comorbid Conditions and Geriatric Assessments as Screening Tools to Guide Treatment
Ongoing treatment for comorbid conditions, such as diabetes, pulmonary disease, and heart disease, may result in drug interactions when chemotherapy is introduced. Chronic diseases, such as renal or liver disease, may alter the pharmacokinetics and pharmacodynamics of chemotherapeutic agents. These changes as well as alterations in drug absorption, distribution, metabolism, and excretion may result in greater toxicities among older cancer patients.15, 16
Consequently, older adults are less likely to receive optimal doses of chemotherapy compared with younger patients because of toxicities and complications.17, 18 However, treatment trials seldom adjust for comorbid conditions or organ decrements when considering treatment modalities.3, 16, 19–21 Careful assessment of comorbid conditions6, 22 and organ function and how these factors may lead to subsequent suboptimal treatment dosages among older patients warrant further research. Under some circumstances with comorbidity and altered organ function, it is essential to consider palliation and supportive care as the best course of management for the older patient rather than suboptimal levels of curative treatment.
Geriatric oncologists propose using the Comprehensive Geriatric Assessment (CGA) to determine which older cancer patients can benefit from treatment and which patients may benefit more from palliative care as the preferred treatment approach.1, 6, 22 This multidimensional assessment includes an evaluation of physical functioning, including activities of daily living (ADLs) and instrumental activities of daily living (IADLs), comorbid conditions, cognitive performance, psychological and nutritional status, social support, a review of current medications. and the presence of geriatric syndromes.1, 8, 19, 20, 23 The CGA identifies reversible or mutable conditions, predicts treatment toxicity, and determines the amount of family support available and pairs it with what will be needed to implement the therapeutic plan. Unfortunately, few formal tests have been conducted of the CGA with treatment protocols, and research is needed to determine the predictive capacity of the CGA for guiding and monitoring treatment decisions among older cancer patients. An associated concept, frailty, also may inform the manner in which the CGA is assessed24; and the correlations between comorbidity and geriatric syndromes are beginning to be evaluated.25
Functional Status and Its Impact on Older Cancer Patients
Loss of physical function with resultant disability occurs with age. Over 60% of individuals ages 65 to 74 years have some disability, 65% of individuals ages 75 to 79 years report disability, and >76% of individuals aged ≥80 years report some disabling conditions.26 Consequently, patients with no or few ADL or IADL limitations may be able to tolerate full doses of treatment but should have frequent monitoring to identify potential adverse events.6, 27–29 However, Maione and colleagues documented that global quality of life, performance status, and IADL were prognostic factors for the survival of elderly patients.30
Among older cancer patients, losses in physical function and disability are associated with losses of functional reserve, which, in the presence of chemotherapy, increase the likelihood that these patients will experience toxic side effects.10, 16, 26 However, studies are needed to define the tolerance and response to treatment among older patients with various levels of disability and to conduct subanalyses describing how treatments impact patients' functional reserves and their ability to recover their levels of functioning after the end of treatment.31 Finally, the interplay between function, dose delays, reductions, and drug stoppages needs to be assessed carefully. Such information can help to estimate life expectancy and treatment tolerance and can establish a common classification of physical function to be used to plan care for older adults.
Screening for Psychological and Social Factors That Influence Treatment
Among older patients, social factors, such as the availability of a spouse to provide home care, widowhood, fixed incomes, and transportation, and living arrangements, such as assisted living, should be considered in developing cancer treatment plans.32 Radiation therapy may be inappropriate for older patients who cannot mobilize transportation or the social, emotional, or psychological support required for daily administrations. Home care also may be compromised.32–34 Blanchard-Fields et al reported that older adults are more focused than younger adults in solving instrumental problems, which means they can identify ways to adapt to their cancer treatment.35 Depression may be associated not only with functional decline for the older adult with health status problems but also with the need for more social support and family care.1, 36, 37
Maintaining physical and social function and managing symptoms through psychosocial interventions may enable older patients to receive and respond to a course of chemotherapy.36–38 Future research should assess the social and psychological states of older cancer patients who are undergoing treatment and should consider supportive interventions to facilitate their adherence to treatment protocols and adjustment and participation in palliative care when curative treatment is not adequate. Patient preferences for treatment are an essential consideration for older adults. Screening and assessment of psychosocial factors are essential when treatment plans are made.
Assessment of the cognitive status of older cancer patients is important in developing a cancer treatment plan. Older patients with mild cognitive deficits may experience greater declines with treatment and may recover cognitive performance more slowly. Older patients with deficits in hearing and vision, memory loss, or cognitive deficits will have difficulty participating in treatment regimens and especially in newer regimens, which that may involve oral agents. Oral agents require patients to follow complex dosing, recognize signs of toxicity, and seek help in response to early complications so that doses can be adjusted and outcomes, such as hospitalizations, can be avoided.15, 39
Treatment and older cancer patients
Older cancer patients face both clinical and broader institutional barriers to appropriate treatment and are less likely to have their cancer staged,3, 10 and they may receive less aggressive treatment (ie, subtherapeutic dosing). Older breast cancer patients are less likely to receive auxiliary lymph node dissection, adjuvant radiation therapy, chemotherapy, or hormone therapy.3, 17, 40 Furthermore, older patients may not be referred to comprehensive cancer centers or offered participation in clinical trials. Assessments like those described above can form the basis for determining eligibility for trials and can open communication regarding the interest of older patients in trial participation and referral to larger centers for second opinions or treatment plans.27, 41
Older patients, when they are selected carefully, appear to tolerate and respond well to cancer treatments.42 Although evidence is limited, older patients derive benefit from adjuvant therapies provided they have a life expectancy >5 years.3
Older patients who have undergone pulmonary resection (up to age 80 years) and treatment for colorectal cancer, breast cancer, prostate cancer, or non-Hodgkin lymphoma all have tolerated and shown positive responses to their treatments.19, 22, 27, 40, 43–45 Radiation therapy with short treatment time and reduced tissue toxicity appears to be beneficial for selected patients.46 Older patients with good health status may tolerate molecular-targeted therapies either alone or in combination with chemotherapy.41, 47
The treatment and management decisions for older cancer patients should be guided by treatments for comorbid conditions, organ function, frailty, and cognitive status. The International Society of Geriatric Oncology16, 19, 48 and the National Comprehensive Cancer Network23 have concluded that older patients with good health status can benefit from treatment, although some may require reduced dosing because of intolerance.28, 49, 50 Thus, chronological age alone should not be viewed as a barrier to treatment.
The interactions among functional status, frailty, and cancer treatment deserve further investigation. For example, how are indicators of frailty, such as anorexia, weight loss, fatigue, inactivity, sarcopenia, osteopenia, and deconditioning, exacerbated by treatments like chemotherapy or radiation10; and, specifically, which protocols are more toxic and have sustained deleterious effects? Such information is needed so that older cancer patients can make informed choices regarding their treatment options. It is important to determine the level of frailty or dysfunction that should be used to consider the exclusion of older patients from treatment. Future research should focus on the development of evidence to determine how treatments exacerbate these conditions, which, in turn, may extend recovery time15 or lower the quality of life to the point at which the consequences of treatment outweigh the benefits. The point at which palliation should be added to care also should be defined. Side effects, such as pain, fatigue, nausea, insomnia, and neutropenia, have been managed less aggressively and appropriately in the older adult.15 Supportive care medications should be prescribed and consideration should be given to reduced dosage or ‘light’ treatment.22, 49 Frail older patients and those with ≥3 more dependencies in ADLs, severe comorbidities, or the presence of other geriatric syndromes may not be offered therapeutic treatment, but they may be offered supportive symptom management and palliation.4, 10
For those older cancer patients who are not suited for therapeutic approaches because of health status, palliative care should be added to their care. It is essential to guide patients and families to palliative care in which they are assisted with decisions, support and communication are facilitated between providers and patients, and families are encouraged so that goals of care can be reassessed. The levels of evidence to inform such choices currently are not available. Below, we focus on areas to be considered when treatment plans are being developed.
Adverse Effects and Side Effects Management
The pattern, severity, and management response of older adults to the toxic and adverse effects of treatment have not been well documented.51 Few psychosocial interventions for symptom management have been described. It is important to determine whether age differentiates among patients according to their responses to symptom management interventions. A test of the moderating effects of neutropenia on the impact of a cognitive behavioral intervention to reduce symptom severity indicated that, when age was included as a variable along with neutropenia in the model, older patients who were exposed to the experimental intervention reported greater symptom severity. No age effect was observed when neutropenia was not included in the model. Identifying how age influences symptom severity endpoints and the moderating effects of consequences, such as neutropenia, is essential.52
In a trial of a psychosocial intervention, patients aged ≤45 years and those aged ≥75 years responded differently to cognitive behavioral interventions to manage cancer treatment side effects delivered by nurses compared with interventions that were delivered either by an automated voice response system or by social workers. Although no differences were observed among patients ages 46 to 75 years, the youngest group (aged <46 years) reported significant reductions in symptom severity using the automated voice response system or the social workers, whereas patients aged >75 years reported greater reductions in symptom severity when the intervention was delivered by nurses.53 These differences point to the importance of understanding how or whether age influences patients' responses to behavioral interventions for side effects because of cancer treatment.
Challenges for Behavioral Researchers
Given the aging of the population and the limited research on interactions between cancer treatments and the response of older patients, research needs to be completed to understand the consequences of new therapeutic regimens. If cognitive status is altered, then this may limit patients' abilities to respond to behavioral interventions that deliver education, counseling, decision making, and communication strategies.39 Similarly, tests of interactions between age, comorbid conditions, physical function, and treatment modalities may help to isolate how age and these conditions affect outcomes. Is it age alone, or does age in the presence of 1 or more of these conditions pose a synergistic effect on responses to treatment? It is important to determine the point at which certain comorbid conditions and compromises in physical function, in the presence of different chemotherapy protocols, produce negative patient reactions. When launching these trials, both behavioral and clinical researchers will need to monitor pretreatment and post-treatment states: not only clinical characteristics, but the impact of these drugs on organ function, symptom experience, physical function, and cognitive performance. We need to have guidelines to determine when palliative care is the best approach for the older patient.15, 54
To participate in treatments, older cancer patients may require the involvement and support of family members. Given the lack of evidence to guide treatment of older adults, providers rely on clinical impressions to make treatment decisions about older cancer patients.1, 16, 27, 28, 43, 55 Behavioral research needs to examine how and when decisions are made, determine who makes treatment related decisions (patients, family, providers)32 and determine the premises upon which these decisions are based. Decisions should be based on the physical or cognitive health of the older patient, patient preferences, the costs of treatment, and the benefits weighed against the toxicities and side effects.
When the patient cannot tolerate treatment, care providers need to ensure that there is an adequate plan of palliative care. Patient decisions to accept palliation rather than active curative treatment also warrant further study.56 A focus on palliative care is needed to ensure the best quality of life as older adults reach the end of their life. Professionals need to assist with decision making and management to establish appropriate palliative care goals and patient preferences for care. Frailty, comorbidities, and psychosocial deficits add to the complexity of palliative care.57 Referral to palliative care is important at appropriate phases of care. Support and resources for patients and their caregivers are required to assure comfort and, finally, a peaceful death.58–60
Geriatric oncology is an emerging field that requires the integration of clinical and psychosocial factors into comprehensive treatment planning. Cognitive and functional performance as well as the emotional affect of the older patient should be assessed and incorporated into treatment plans. It will be important to balance treatment arms according to clinical, functional, and cognitive indicators as these models are examined through trials. A priority research theme will be to explore how, for a site and stage of cancer, a treatment protocol with known efficacy interacts with comorbid conditions, physical function, geriatric syndromes, and cognitive and psychological states to produce treatment outcomes that are acceptable to patients. We need to determine the patients for whom these protocols are and are not acceptable. Under these circumstances, older patients and their families need to be informed of the risks and potential benefits that may be derived from treatment. Patients need to be engaged actively in making treatment decisions. When treatment is not recommended, patients and their families need the best guidance and support to receive maximum benefit from palliation.
Innovative techniques for use with the older patients, such as telephone-based automated voice response systems or web-based approaches, could be considered as a means to monitor more frequently symptoms, temperature, hematologic parameters, physical function, depressive affect, cognition, and, if appropriate, adherence levels to newer oral therapeutic agents. Finally, the burdens that these treatments place on the family, particularly as they relate to employment, insurance coverage and other economic and social dimensions, should be determined.
One important step for future research will be the development of patient-reported measures that are responsive to the needs of the older patient to accompany established clinical parameters. Such measures should precise and sensitive to change in their ability define treatment outcomes also should chart the course, time, and extent of recovery.61, 62 CGA could be used to predict the severity of toxicity and overall survival.63
Evidence from this review suggests that chronological age alone is an inadequate indicator to determine the clinical and behavioral response of older patients to cancer treatment. Each age cohort brings a wide range of comorbid conditions, depressive affects, physical, social, and cognitive limitations and other indicators of frailty and associated indications of organ decrements, or geriatric syndromes. It is important to understand how variations in each of these indicators narrow with successively older patient cohorts. On the basis of this review, we believe that cancer treatment and palliative care among older patients represent areas for close collaboration among behavioral, clinical, and geriatric oncology researchers and the patients themselves.
Cancer and aging are dynamic, multidimensional processes that pose challenges to older patients and require multidisciplinary research teams. Concomitant with that is a need for behavioral research to partner with clinical geriatric oncology to develop the science for the best treatment, palliative care, and quality of life for our growing population of aging cancer patients. There is much work to be completed in the treatment of the older patient with cancer and for palliative care in the final phases of care.
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