Cancer in the Elderly
Biology, Prevention, and Treatment
Summary of Key Points
Epidemiology of Aging and Cancer
• The older population continues to expand as a result of reduced mortality and birth rates. Currently 60% of all malignancies occur in persons aged 65 years and older, and this proportion is expected to rise to 70% by the year 2030. Although cancer-related mortality is declining among younger persons, it is increasing among the oldest persons.
• It is of special interest that cancer appears to affect mainly older persons who are otherwise healthy and would have lived longer were it not for the cancer.
Aging and Carcinogenesis
• Carcinogenesis is a time-consuming process, the end-product of which—cancer—is more likely to develop at an advanced age.
• Aging is associated with molecular changes that mimic carcinogenesis; older cells are primed to the effects of environmental carcinogens.
• Aging is associated with environmental phenomena such as immune senescence or proliferative senescence that favor the development of cancer.
Aging and Cancer Biology
• The biology of the tumor cells (e.g., the prevalence of multidrug resistance protein 1 in acute myeloid leukemia increases after age 60 years, causing a worse prognosis).
• The aging of the patient: an age-related increase in circulating concentrations of interleukin-6 (IL-6) may favor the growth of lymphomas, whereas hormonal senescence may inhibit the growth of breast cancer.
Assessment of the Older Person
• Aging involves a progressive shortening of life expectancy and reduction in the functional reserve of multiple organ systems.
• Personal and social resources to cope with stress may become more limited.
• Reduced life expectancy and reduced stress tolerance lessen the benefits and enhance the risks of medical intervention.
• A comprehensive geriatric assessment (CGA) to evaluate the patient’s function, comorbidity, cognition, nutrition, medications, and living resources is a currently available, reliable instrument for predicting life expectancy and the risk of treatment-related complications.
• The CGA may unveil preexisting situations such as undiagnosed disease, poor nutrition, depression, or lack of adequate social support that are remediable and may influence the outcome of treatment.
• A number of laboratory tests, including the circulating levels of IL-6 and d-dimer, along with tests of physical performance, may complement the CGA.
Cancer Prevention
• Older persons may be primary candidates for chemoprevention of cancer, but none of the current chemopreventive agents has demonstrated efficacy definitively.
• Screening asymptomatic patients for cancer of the breast, large bowel, and lung appears reasonable when the life expectancy is 5 years or longer.
Cancer Treatment
• Surgery: Age by itself, until 100 years, does not appear to increase the risk of surgical mortality, although the risk of surgical complications and length of postoperative hospitalization increase with age. Age is a definitive risk factor for mortality related to emergency surgery.
• Radiation therapy: Tolerance for radiation therapy seems to remain high, even for persons aged 80 years and older.
• Cytotoxic chemotherapy: The main pharmacologic changes of age include decreased excretion of drugs and of their active metabolites from the kidneys; decreased volume of distribution of water-soluble drugs, which may in part be accounted for by anemia; increased susceptibility to myelodepression, mucositis, and peripheral and central neuropathy; and cardiomyopathy. The National Cancer Center Network has issued the following guidelines for the management of older patients with cancer:
1. Which of the following factors does not increase the risk of mortality of older patients with cancer?
2. Which laboratory tests may estimate the physiological age of older persons?
3. The incidence of cancer increases with age because:
A Carcinogenesis is a time-consuming process.
B Older tissues are more sensitive to environmental carcinogens than younger ones.
4. Which of the following guidelines is not part of the National Comprehensive Cancer Network guidelines for the management of older persons?
A Maintain hemoglobin at 12 gm/dL
B Use filgrastim or pegfilgrastim in patients aged 65 years or older who are treated with cyclophosphamide, doxorubicin, vincristine, and prednisone
C Perform some form of geriatric assessment in all persons 70 years and older
D Adjust the dose of chemotherapy to the glomerular filtration rate in patients 65 years and older
1. Answer: B. In the model proposed by Lee et al., dependence in IADLs, decreased ability to push and pull heavy objects, and renal insufficiency were associated with increased mortality risk at 4 years. Cardiovascular and respiratory comorbidity also determined increased mortality risk.
2. Answer: A. Several studies have demonstrated that the serum concentration of IL-6 is associated with increased risk of mortality, functional dependence, and geriatric syndromes. The value of one time determination of leucocyte telomere length is uncertain because of inter-individual variability. Although serum insulin and cortisol levels are generally increased with age, they have not been correlated with any adverse outcome.
3. Answer: D. The association of cancer and age is explained by all three mechanisms. Aging tissues undergo preneoplastic molecular changes such as changes in DNA methylation and histone deacetylation. Both chronic inflammation and increased circulating levels of insulin may promote cancer growth and cause carcinogenesis.
4. Answer: A. The guideline related to hemoglobin levels was removed after the report of the potential complications of erythropoietin.
