Due to the aging of the population cancer in the older person is an increasingly common problem(1). The questions include:
- Why does the incidence of cancer increase with age?
- Are neoplasms in older individuals different from those that develop in the younger ones?
- Is there a role for primary and secondary cancer prevention in older individuals?
- How should one manage cancer in the presence of reduced life-expectancy and decreased tolerance of stress?
Cancer incidence and age
At least three reasons account for the increased incidence of cancer with age: duration of carcinogenesis, increased susceptibility of aging tissues to environmental carcinogens, and changes in the bodily environment that favor cancer development and growth(1).
A number of experimental studies indicate that older tissues are in a condition of advanced carcinogenesis that makes them more susceptible to environmental carcinogens(2). Epidemiological studies indicate that this may be the case in humans as well.
Age is a risk factor for the development of acute leukemia from doxorubicin(3). In a longitudinal study the development of cancer was three fold more common in individuals who had the shortest telomere length (which is inversely proportional to physiologic age)(4).
Age is associated with chronic inflammation that may increase the formation of tissue carcinogens and inhibit the function of natural killer cells, that also decreases with age(5).
Endocrine senescence may have opposite effects of tumor growth. Decreased production of sexual hormone may slow the growth of some endocrine dependent cancers such as breast and prostate cancer. At the meantime insulin resistance is associated with increased circulating levels of insulin which acts as a powerful tumor growth factor(6).
Cancer biology and aging
To study potential changes in cancer biology one needs to examine both the cancer itself and the tumor-host interactions.
In the case of acute myelogenous leukemia the prevalence of adverse prognostic factors increases with age(7). These include both unfavorable cytogenetics and genomic changes and increased prevalence of multidrug resistance.
Recent studies showed that the prevalence of the so called ABC lymphomas, that represent a more chemotherapy resistant subtype of large cell lymphoma, also increases with age(7).
In the case of breast cancer, the prevalence of well differentiated hormone receptor rich tumors increases with the patient’s age.
Very little is known at present of changes in tumor host interactions Experimental studies suggest that the growth rate of highly immunogenic tumors is increased and that of low immunogenic tumors is decreased with the animal age, but it is not clear how these experimental models relate to the clinical situations(7).
Not surprisingly, the prognosis of acute myeloid leukemia and of large cell B cell lymphoma worsens with age.
More surprisingly, the risk of breast and prostate cancer related mortality also increases with the patients’ age after age of 65(8-9). It is not clear to which extent these results are due to biological changes or to inadequate management.
In any case, two conclusions are clear: the biology of some tumors at least changes with the patient’s age, and most cancers are lethal for the older person. A patient’s age is not an excuse for complacency in cancer treatment.
Primary and secondary prevention
of cancer in older individuals
Primary cancer prevention includes removal of environmental carcinogens and chemoprevention. Older individuals appear as ideal candidates for primary prevention, given the increases susceptibility of aging tissues to environmental carcinogens. In other words, it is never too late to quit smoking and to adopt a healthy diet.
Chemoprevention of cancer at present has limited clinical use, and includes chemoprevention of breast cancer with selective estrogen receptors modulators or aromatase inhibitors, chemoprevention of prostate cancer with 5-a hydroxylase inhibitors, chemoprevention of cancer of the head and neck with retinoic acid, and chemoprevention of cancer of the large bowel with aspirin in low doses(7).
Except for low doses of aspirin that are commonly used also for prevention of coronary artery disease, it is difficult to estimate the benefits/risks ratio for all other forms of chemoprevention in the older person.
Secondary cancer prevention includes early diagnosis in asymptomatic patients.
Early diagnosis of breast, colorectal, and non small cell lung cancer may reduce the cancer related mortality in the general population(7).
The benefits of screening asymptomatic individuals aged 80 and older for cancer is controversial(10). This intervention should be limited to those with a life expectancy of five and more years.
For all other individuals the risks of screening that include false positive results and over-diagnosis may overtake the limited benefits.
Treatment of cancer in the older aged
person
As already mentioned, cancer is lethal for elderly individuals.
The risks of all forms of cancer treatment, including surgery, radiation therapy, and systemic therapy increase with age, but age itself should never be considered a contraindication to life-saving interventions. Instead treatment related decisions should be based on the following parameters:
- aggressiveness and stage of cancer;
- effectiveness of treatment;
- life expectancy of the patient;
- patient’s tolerance of treatment.
Clearly, the determination of physiologic age, that is of individual life expectancy and functional reserve, is essential to deliver safe and effective cancer treatment(7).
Currently, the assessment of physiologic age is based on a comprehensive geriatric assessment (CGA). The CGA involves function, as ability to perform basic activities of daily living (ADL) and instrumental activities of daily living (IADL), presence of geriatric syndromes and polymorbidity, Polypharmacy, mental, emotional and socio-economic status(7).
In addition to providing an estimate of physiologic age, the CGA allows the practitioner to unearth situations that may compromise the treatment, such as absence of an adequate caregiver, and risk of malnutrition(7,11).
Some laboratory tests, including the “inflammatory index” and the length of the leukocyte telomeres, have been proposed as complementary of the CGA, but have not been validated yet.
In addition, the safety of the treatment may be improved with appropriate measures(11).
It is well known that older individuals are more susceptible to chemotherapy-induced myelotoxicity and mucositis, and both complications are preventable with pharmacological intervention.
Likewise, age is a risk factor for osteoporosis from estrogen or androgen deprivation, and this complication may be fully preventable with proper ingestion of calcium and vitamin D and with the use of bisphosphonates.
Despite these precautions it is important to remember that age is also a risk factor for late complications of cancer chemotherapy, that include fatigue, neuropathy, cardiac failure, acute leukemia, and possibly memory disorders.
The prevention of these complications is an area of active research.
Conclusions.
The incidence and prevalence of cancer increases with age and older age is a risk factor for cancer death.
Cancer screening may be effective in selective elderly, that is those with a life expectancy of 5 years and longer.
All forms of cancer treatment may be beneficial to older individuals irrespective of chronologic age. The treatment-related decisions should be based on cancer aggressiveness and stage, effectiveness of treatment and the patient’s physiologic age.