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Cancer in the Elderly: Biology, Prevention, and Treatment


Summary of Key Points

  • Physiologic Changes of Aging

  • Cancer and aging share common biologic and cellular mechanisms such as genomic instability, deregulated energetics, and cellular senescence.

    † Deceased.

  • Older adults have age-related changes in all organ systems that decrease the tolerance to both cancer and its treatments.

  • Geriatric Assessment in Oncology

  • The geriatric assessment is a multidimensional evaluation of an older adult's physical function, cognition, comorbidity, psychological status, social functioning, and nutritional status.

  • The geriatric assessment can be used to identify areas of vulnerability for which targeted interventions can be applied.

  • Clinical Applications of the Geriatric Assessment

  • Information obtained through the geriatric assessment can help the clinician assess the patient's life expectancy and assess the benefits and harms of oncologic interventions.

  • The geriatric assessment can be used to estimate life expectancy and hence assist in weighing the potential benefits and risks of screening and treatment.

  • Predictive models have been developed in order to estimate the risk of severe chemotherapy toxicity in older adults and can be useful for shared decision making.

  • The information obtained from the geriatric assessment can lead to the implementation of oncologic and nononcologic interventions aimed at improving care.

  • What the Future Holds

  • Innovative trial designs and new geriatric-specific outcomes are needed to fully understand the risks and benefits of cancer treatment in older adults.

  • Understanding biologic and cellular aging by measuring biomarkers of aging could be a potentially useful tool to assess the fitness of older adults with cancer.

  • Several models of care in geriatric oncology exist, and oncologists treating older adults with cancer should attempt to implement the one that best fits their environment.

Cancer is a disease of aging. In 2015 there were an estimated 9 million new cancer cases and 5 million cancer deaths among individuals aged 65 and older worldwide. In the United States, the number of older adults will reach 83.7 million by 2050, representing 21% of the total population ( Fig. 60.1 ). This demographic transition will bring about an exponential increase in both the number of newly diagnosed older adults with cancer and older cancer survivors. To face the needs of this growing population of patients with cancer and to improve the way cancer care is delivered, the entire workforce must enhance its geriatric competence. This chapter reviews the aspects of aging that are most relevant for the practice of oncology and their relevance for the prevention and treatment of cancer in older adults.

Figure 60.1
US population aged 65 years and older.

(Data from United States Census Bureau. Projections of the size and composition of the U.S. Population [Paris] . 2015.)

Fundamental Science

Cancer and aging represent two different manifestations of an accumulation of cellular damage and mutations, and several of the cellular processes that constitute the hallmarks of aging are also hallmarks of cancer. Shared mechanisms of both cancer and aging include genomic instability, deregulated cellular energetics, alterations in intercellular communications and cellular senescence. Cellular senescence can be triggered in response to several stressors, such as tissue injury, DNA damage, oncogene activation, and telomere dysfunction. Cellular senescence exerts both anticarcinogenic and procarcinogenic effects because it can lead both to the suppression of transformed precancerous cells and to the promotion of tumor growth via cell-autonomous and nonautonomous pathways. As the replicative capacity of self-renewing stem cells declines with age, senescent cells accumulate and develop a secretory phenotype that can stimulate surrounding cells and promote oncogenesis. Senescent cells have been shown to provoke proliferative changes in neighboring cells and to induce epithelial-mesenchymal transition. Another fundamental link between aging and cancer is DNA damage and the derailment of genome guardian mechanisms. The clearance of damaged cells by cell-intrinsic checkpoints can suppress carcinogenesis but has the potential downside of impairing tissue maintenance and promoting aging. Ultimately, the aging-associated accumulation of damage may lead to tissue dysfunction and to the selection of malignant stem cell clones. The last decades have also provided solid evidence demonstrating the importance of the interaction among cancer, aging, and the immune system. In older adults, the ability to respond and react to cancer is reduced because of dysregulated immunity, or immunosenescence, which is characterized by depressed T-cell function. At the same time, older adults have a blunted adaptive immune response, which leads to a reduction in the capacity to detect and remove mutated cells and an increase in autoantibody production. These changes in the immune system may not be related only to the pathogenesis of cancer, but also to the response to and tolerance of chemotherapy and other treatments.

Physiologic Changes of Aging

Cancer and its treatment can have negative effects on the fitness of individuals and cause deconditioning and functional decline. This is of particular concern in older patients who have preexisting age-related changes in the cardiorespiratory and musculoskeletal systems. Older adults also have lower maximal heart rates, reduced contractility, and decreased stroke volume, all of which lead to a decreased cardiac functional reserve in demanding situations. In the respiratory system, decreased lung volume, impaired mucociliary clearance, and a proinflammatory microenvironment also are present, which increase the risk of chronic damage and infection. Sarcopenia, an age-related condition characterized by loss of skeletal muscle mass and function, can also alter the ability to tolerate treatment and hamper recovery from stressful events such as surgery or chemotherapy. Changes in intestinal motility and in mucosal protective mechanisms may lead to variable absorption of oral chemotherapy and to a higher risk of mucositis. Aging is associated with a decline in hepatic volume and hepatic blood flow, which in turn leads to a decrease in the capacity to metabolize and excrete drugs. In addition, renal function and renal reserve decrease with age, mainly owing to vascular changes leading to a loss of cortical area. This loss of renal function has a significant impact on the pharmacokinetics of cytotoxic drugs, and it should be taken into account in prescribing chemotherapy in older adults. Serum creatinine is a poor marker of renal function in older adults because of a simultaneous decrease in muscle mass, and usual glomerular filtration rate calculation methods may not be as precise in this patient population. Nevertheless, in every patient creatinine clearance should be calculated with the abbreviated Modification of Diet in Renal Disease (MDRD) or Cockcroft-Gault equation, because abnormalities in results of these formulas have been shown to correlate with a higher risk of chemotherapy toxicity.

Geriatric Assessment in Oncology

In general, older adults with cancer are assessed with the same tools that are used in younger patients. Presently, oncologists assess functional status by assigning a Karnofsky Performance Status (KPS) score or Eastern Cooperative Oncology Group (ECOG) Performance Status. These generic scales are used in all adult cancer patients, regardless of age, to estimate functional status. This information is used to determine a treatment course, assess eligibility for clinical trials, and predict treatment toxicity and survival. In contrast, the geriatric assessment is a multidimensional diagnostic evaluation aimed at providing a comprehensive overview of an older patient's functional status, cognition, psychological status, social functioning, and nutritional status ( Table 60.1 ). Each of the domains included in the geriatric assessment is an independent predictor of morbidity and/or mortality in the geriatric population. This comprehensive evaluation provides valuable information not provided by KPS or ECOG performance scores and enables identification of important areas of vulnerability in patients with normal performance status ; however, this assessment is not commonly taught in oncology training or used in oncology practice.

Table 60.1
Geriatric Assessment Tools and Measures
Domains Tools and Measures
Functional status Activities of Daily Living
Instrumental Activities of Daily Living
Number of falls
Timed Up and Go (TUG)
Comorbidity Cumulative Illness Rating Scale–Geriatrics
Charlson Comorbidity Index
Polypharmacy Total Number of Medications
Beers Criteria
STOPP criteria
Nutritional status Body mass index
Unintentional weight loss in last 6 months (%)
Mini Nutritional Assessment (MNA)
Cognitive function Blessed Orientation-Memory-Concentration
Mini Mental State Examination (MMSE)
Mini-Cog
Psychological status Mental Health Inventory–17 (MHI-17)
Geriatric Depression Scale (GDS)
Personal Health Questionnaire (PHQ–2 and PHQ-9 )
Generalized Anxiety Disorder–7
Social support Medical Outcomes Study questionnaire
Zarit Caregiver Burden Interview

Functional Status

Functional status refers to the ability to perform tasks needed to function independently at home and in the community. These are usually divided into activities of daily living (ADLs), including bathing, dressing, toileting, maintaining continence, transferring, and feeding ; and instrumental activities of daily living (IADLs), including housekeeping, cooking, managing finances, transportation, using the telephone, and self-administering medications. The need for assistance with at least one ADL or IADL is found in up to 50% of older adults with cancer; and 25% of patients with a KPS score of 80% to 100% are impaired in at least one IADL. ADL and IADL deficits are also related to increased risk of chemotherapy toxicity and worse cancer-specific survival.

Gait speed is a simple performance-based functional measure shown to predict survival in community-dwelling older adults and in older adults with cancer. Abnormalities in the Timed Up and Go (TUG) test (which is performed by asking the patient to rise from a chair, walk 3 meters, turn around, walk back to the chair, and sit down again), in the Short Physical Performance Battery, and in gait speed predict worse survival, treatment-related complications, and functional decline in older adults with cancer.

The presence of falls is an indicator of poor functional status. Falls in older adults with cancer are common, and a history of falls is correlated with a higher risk of chemotherapy toxicity. Asking older adults about a history of falls and assessing risk factors for falling is important because interventions, such as physical therapy, may lead to improved fall prevention.

Comorbidity

Comorbidity is defined as a medical condition that coexists with an index condition. Comorbidities are highly prevalent among older adults with cancer, with 25% having four or more concurrent conditions. An increased burden of comorbidity is associated with poorer overall survival (OS) in several types of cancer. Comorbidity has a significant impact on the tolerance to cancer treatments, and patients with comorbidities are less likely to be referred to a medical oncologist or to receive chemotherapy. Comorbidities have been shown to have a negative impact on prognosis and treatment outcome in patients with cancer. Furthermore, comorbid conditions may require treatment with multiple medications, predisposing the patient to the risks of polypharmacy and drug interactions (see later). Currently, there is no gold standard for the measurement of comorbidity in patients with cancer. The number and severity of comorbidities can be assessed with indices used to determine the risk of mortality associated with comorbidity in older patients, such as the Charlson Comorbidity Index (CCI) or the Cumulative Illness Rating Scale (CIRS).

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