Introduction: cancer in the elderly

Article Outline

• Acknowledgements
• Copyright

As I give thought to the matter, I find four causes for the apparent misery of old age: first, it withdraws us from active accomplishments; second, it renders the body less powerful; third, it deprives us of almost all forms of enjoyment; fourth, it stands not far from death.… Cicero, On Old Age

WHEN Marcus Tullius Cicero was writing in the first century BC, technology had not yet had an impact on the natural history of disease. Otherwise, he would have added a fifth source of misery of old age that is with us now-having life-extending treatment withheld on the basis of age. Ageism, or bias against old people, is a part of the culture of the 21st century. Any form of bias is inherently reprehensible; however, ageism that limits the use of medical technology to extend lives, undermines the implied contract between a physician and his/her patient, namely that the physician will always act in the best interests of the patient. That contract is not a license for a paternalistic (“the doctor knows best”) kind of management. It implies that the physician will share his knowledge with the patient and that together they will formulate a treatment strategy based on the patient being well-informed of the potential risks and benefits of alternative approaches. Sadly, in nearly every instance where it has been examined, very large numbers of older patients who might benefit from treatment are not offered treatment, and the fraction of such patients increases with increasing age. Much age bias is based on misinformation. Few physicians know the median life expectancy of older patients. A person in average health surviving to age 75 years can now expect to live on average another 11 years, a healthy 85-year-old has a 6-year median life expectancy. These numbers exceed the average survival durations of most untreated cancers. Still, older people remain at risk of having their lives shortened by cancer and, conversely, stand to have their lives extended by successful treatment.

In general, survival after a cancer diagnosis declines as age increases. There are several reasons for this. Failure to treat older patients is but one. Underuse of screening, less aggressive diagnostic evaluation, and less aggressive surgery are others. Another is the introduction of ad hoc anticipatory dose reductions and schedule alterations of regimens with established efficacy, often based on spurious rationale. One of us once had a 72-year-old man referred to us with stage II diffuse large cell lymphoma after having relapsed “on a modified CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen.” When additional inquiries were made of the nature of the therapy that was actually delivered to this patient, the following facts emerged. The prednisone had been withheld because the patient had type II diabetes controlled with diet alone, because the physician was afraid the diabetes would be difficult to control. The doxorubicin had been withheld because the patient had ankle edema (from peripheral venous disease, as it turned out) but the physician was afraid the doxorubicin would damage the heart and cause heart failure (which the patient did not have). The vincristine was also withheld because the physician was afraid that it would accelerate the development of diabetic peripheral neuropathy. As a result, this patient with a potentially curable malignancy had received only single-agent cyclophosphamide, a decidedly inferior treatment, while the patient and his family believed he had received a modified CHOP regimen that just had not been effective. It is impossible to estimate how many older patients are permitted to die from their cancer because it is more acceptable to die from a malignancy than to risk toxicity.

Also contributing to inferior survival in older patients with cancer is the different natural history of some cancers in the elderly. Although not nearly enough is known about differences in cancers of a particular histologic type as a function of age, clinical observations help us make some predictions in this regard. Unquestionably, acute myeloid leukemia is genetically distinct, biologically more aggressive, and relatively refractory to treatment in older people compared with younger people. By contrast, breast cancer appears to be a more indolent disease in the elderly. Colon cancer appears to have a similar natural history in older and younger patients. However, for many types of cancer, neither clinical nor genetic data have been generated to adequately assess age-related differences.

Finally, some older patients die with cancer but not because of cancer. Comorbid illness increases with age, and the presence of other life-threatening illnesses can further compromise the ability of a patient to endure the stresses of cancer and its treatment. Here, too, we lack sufficient information to devise a way forward. Moreover, we frequently do an inadequate job of assessing physiologic reserve in older people. We all have had the experience of managing an older patient with cancer who appeared in otherwise good health, but in whom treatment precipitated a calamitous multisystem decompensation. Such patients had borderline physiologic reserve that was barely maintaining homeostasis and the addition of cancer therapy was just enough to disrupt homeostasis altogether. On the other hand, some older patients in poorer health surprise us all by tolerating treatment well. At the moment, no reliable tools are available that predict how a particular patient will fare.

This issue of Seminars in Oncology was organized to provide the reader with a snapshot of what we know now, and what we need to know to develop an effective approach to treating older patients with cancer. Drs Rosemary Yancik and Lynn Ries first outline the magnitude of cancer in the elderly. The median survival of a person born on January 1, 2001 was about 79 years, 30 years longer than the median survival of a person born on January 1, 1901. So we are living longer. Second, the population is increasing at a rapid rate, perhaps not reaching Malthusian proportions just yet (except in some small pockets of the world); an increasing percentage of the population will be age 65 or older as we move further into the 21st century. So there are more of us living longer as well. Finally, cancer incidence increases dramatically with age, and more older patients with cancer will be in need of treatment. This trend is not just a feature of the United States population, but is occurring in all affluent countries worldwide. The demographics are clear; we cannot ignore the age imperative.

Next Drs Neelima Denduluri and William Ershler describe insights in aging biology that shed light on carcinogenesis and cancer progression in the elderly. The interactions are complex and not intuitively obvious. The aging of the immune system that may on the one hand make a person more susceptible to cancer by reducing immune surveillance, may actually lead to reduced tumor growth and less frequent metastases. Drs Arati Rao, Pearl Seo, and Harvey Jay Cohen then describe methods that may be more successful at assessing physiologic reserve than the Karnofsky performance score. Geriatricians have developed a more accurate measurement of physical reserve capacity and homeostasis using techniques encompassed in a “comprehensive geriatric assessment.” These tools measure medical, functional, affective, social, spiritual, and environmental domains of the older cancer patient and may be useful when applied prospectively to optimize choice of therapy, define the likelihood of treatment success, and predict the effects of treatment on quality of life.

The next two articles evaluate the effects of age on the common therapeutic interventions in cancer patients. Dr Stuart Lichtman describes what is currently known about the influence of the aging process on cancer drug metabolism and pharmacology, as well as the considerable amount of information not yet known. However, application of what is known to make appropriate dose adjustments based on renal and hepatic end organ function is essential to ensure the optimal safety of treatment. Dr Margaret Kemeny then reviews the influence of aging on the assessment of surgical risk and the effects of surgical therapy for the common solid tumors that affect older patients.

The next section contains a series of articles on cancers of particular organ systems in the elderly. Drs Marshall Lichtman and Jacob Rowe review myeloid malignancies; Drs Eric Westin and Dan Longo review lymphoid malignancies; Drs Peter Enzinger and Robert Mayer review gastrointestinal cancers; Drs Aqeel Gillani and Steven Grunberg review head and neck and lung cancers; Drs Gretchen Kimmick and Hyman Muss review breast cancer; and Drs Derek Raghavan and Eila Skinner review genitourinary tract cancer. This section concludes with an article by Drs Andrea Luciani and Lodovico Balducci on an important and understudied area of particular relevance in older patients, multiple primary cancers. It is likely that as-yet-undescribed multiple cancer syndromes are present in the elderly population. Moreover, it has been estimated that as many as 15% of older patients cured of one cancer by surgery alone develop a second malignancy in another organ. Thus, these second cancers cannot be attributed to effects of treatment. Patients with multiple cancers rarely are eligible for current clinical trials, and little systematic study of patients with multiple cancers has been performed.

The final section contains two important articles on matters that are often neglected. Ursula Matulonis has put together an excellent treatise on palliative care, including treatment of pain and depression and end-of-life management issues including advance directives and hospice care. Margot Birke, Esq, a lawyer specializing in elder law, an emerging specialty of law practice, reviews major legal issues facing older patients, their families, and their health care providers, including the assessment of capacity to provide informed consent, advance directives, surrogate decision-making, and rights and privileges associated with government programs such as Medicare, Medicaid, and Social Security.

The editors hope that this issue of Seminars in Oncology will be useful to both the clinician and the laboratory scientist and others interested in the major issues affecting older Americans in general, but especially those with cancer.

Back to Article Outline

Acknowledgements 

The editors are indebted to Linda B. Norton for diligently applying her considerable editorial and management talents to the production of this issue. Without her, this issue would not have adhered to the production schedule and would not have reached its current quality.