Cancer

Although cancer occurs in persons of every age, it is fundamentally a disease of aging. Sixty percent of new cancer cases and two thirds of cancer deaths occur in persons > 65 years (see Figure 72-1). The incidence of common cancers (eg, breast, colorectal, prostate, lung) increases with age. However, incidence of many cancers levels off after age 80, suggesting the possibility of intrinsic resistance to the development of cancer in late life or some selection bias.

The age-related increase in cancer incidence predicts that as the U.S. population ages, cancer incidence will continue to increase. There are several theoretical reasons why cancer incidence increases in the elderly (see Table 72-1): age-related alterations in the immune system (decreased immune surveillance); accumulation of random genetic mutations leading to oncogene activation or amplification or decreased tumor-suppressor gene activity; lifetime carcinogen exposure (especially for colorectal and lung cancers); hormonal alterations or exposure; and long latency periods. There may be increased susceptibility to carcinogens, possibly caused by decreased DNA repair. Multiple genetic changes are necessary for the development of cancer, most clearly exemplified by the stepwise genetic changes shown by many colon polyps progressing to cancer. The exponential rise in many cancers with age fits with an increased susceptibility to the late stages of carcinogenesis by environmental exposures. Lifetime exposure to estrogen may lead to breast or uterine cancer; exposure to testosterone, to prostate cancer. The decline in cellular immunity may lead to certain types of cancer that are highly immunogenic (eg, lymphomas, melanoma).

Controversy continues over whether cancer is less aggressive in the elderly. Growth and metastasis of several types of cancer (breast, colon, lung, prostate) appear to be slower in the elderly. Yet, death occurs with smaller tumor burdens. Reasons for the difference in mortality appear to be complex: Diagnosis is often made later, treatment tends to be less aggressive, and competing causes of death are more likely; all of these factors result in shorter survival in older patients.

Risk Factors and Prevention

The part of cancer prevention we know the most about is the avoidance of toxins that induce or promote cancer. Induction refers to the earliest genetic change induced by a carcinogen. Promotion refers to cell growth induction that fixes and then further alters the genetic abnormality. Carcinogens may alter normal growth-promoting genes (proto-oncogenes), which are permanently turned on. They may also damage growth-suppression genes (tumor suppressors) such that they become permanently turned off. Both may be necessary to create a cancer. Since prolonged exposure is one of the necessary ingredients to both induction and promotion, prevention of cancer in the elderly must begin before people become old. The best evidence strongly recommends avoiding smoking, overuse of alcohol, and exposure to known toxic chemicals. Maintaining a low-fat, high-fiber diet may be helpful.

Hormonal exposure is implicated in the development of breast, prostate, and uterine cancers. Studies have been inconsistent as to whether exogenous estrogen exposure increases breast cancer risk, but the relative risk is probably in the range of 1.3. Early menarche, late menopause, and late or no pregnancies are confirmed risk factors. Estrogenic stimulation of the endometrium, when allowed to go unchecked, increases the risk of uterine cancer 2- to 2.5-fold.

Drugs may also reduce the risk of some cancers. Tamoxifen has recently been approved for breast cancer prevention. Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) appear to reduce the risk of colon cancer. Retinoids may be helpful in reducing the risk of new primary squamous cell cancers in persons with previous such cancers related to tobacco use. The role of antioxidants in preventing cancers remains unclear. Inhibiting the conversion of testosterone to 5--dihydroxytestosterone may prevent prostate cancer.

Screening

Because cancer is more common in the elderly than in younger populations, screening is more likely to detect cancer in older populations. Cancers for which screening has proved beneficial in reducing mortality include breast, cervical, and colon cancer. It is unclear whether immune surveillance of early cancers is effective. Most cancers are poorly immunogenic and are unlikely to raise an immune response with low tumor volumes. With prostate-specific antigen (PSA) testing, prostate cancer is detected at an earlier stage, but most studies have not shown that screening with PSA reduces mortality. Screening for ovarian cancer, even in high-risk women, has proved disappointing.

Most published recommendations for cancer screening focus on populations younger than considered here. Thus, the main concern regarding the elderly is when to discontinue routine screening. No studies show benefit of screening past age 75 for any cancers. Despite the lack of data, recommendations on cancer screening in the elderly have been published (see Table 72-2).

Treatment

Research that focuses on cancer in younger populations may not be applicable to the elderly, the segment of the population at highest risk for cancer, leaving us with a paucity of knowledge on how best to manage cancer in the age group that experiences it most.

Treatment goals must be individualized based not only on treatability of the cancer, but also on comorbid conditions, functional status (one of the best predictors of response and tolerance (see Table 81-3 and Table 81-4), social situation (which may preclude treatments involving travel or expense), and willingness of the patient to tolerate side effects of treatment. Surgery, chemotherapy, radiation therapy, and hormonal therapy are the mainstays of treatment. However, symptomatic and supportive therapy with analgesics, antidepressants, anxiolytics, and antiemetics, as well as support groups and individual and family counseling, must be integrated into treatment programs. Access to support services and to trained health care practitioners varies depending on the patient's geographic location, financial resources, mobility, and support of family and friends. Referral to major cancer centers may prolong survival but may not be the most humane course of action for debilitated and relatively immobile patients.

Age per se is not usually the deciding factor as to whether aggressive treatment is warranted: that decision must assess the likelihood that the cancer will respond to treatment, the extent of spread, comorbid conditions that could limit therapy, and the patient's wishes. Chemotherapy or radiation therapy should be strongly considered in clinical situations in which cure, prolonged survival, or definable palliation can be achieved with these modalities.

Chemotherapy: A variety of older chemotherapeutic drugs remain effective and useful. In addition, newer antineoplastics are becoming more commonly used in the treatment of cancer in the elderly (see Table 72-3). Chemotherapy may be less well tolerated by elderly patients because of kinetic and dynamic changes that occur with age, decreased organ reserve, and poorer wound healing. Comorbid conditions such as diabetic neuropathies, renal insufficiency, heart failure, and decubitus ulcers may contraindicate specific treatments. However, nausea and vomiting from chemotherapy tend to be less intense in the elderly.

Age-related decreases in liver size, blood flow, and metabolic reserve and use of drugs that inhibit cytochromes may inhibit drug metabolism. The neurotoxicity of drugs such as vincristine, cisplatin, and paclitaxel is especially troublesome in the elderly, and severe neuropathies or constipation may result. Hematopoietic toxicity of most drugs and of radiation therapy is increased to some degree. Gastrointestinal toxicities of 5-fluorouracil and doxorubicin may be increased, and frail patients are less able to tolerate short episodes of diarrhea or decreased oral intake from mucositis. Reduced cardiac reserve makes it more difficult for the elderly to tolerate anthracyclines, and decreased renal reserve decreases tolerance to platinum drugs and methotrexate, requiring adjustments in dose or choice of drug. With curable malignancies, great care must be taken not to reduce doses without documented need.

Advancements in hematologic manipulation have made the use of chemotherapy safer in the elderly. For example, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) diminish duration of chemotherapy-induced neutropenia. Erythropoietin is often effective in treating chemotherapy-induced anemia and is well tolerated. Oprelvekin, a nonspecific growth factor for megakaryocytes, has been approved for preventing and treating severe thrombocytopenia associated with chemotherapy. However, oprelvekin prevents, at most, 30% of needed platelet transfusions and often causes significant adverse effects (edema, dyspnea, tachycardia). It should be used with caution in patients at risk of heart failure or with central nervous system tumors. Pamidronate is effective treatment of tumor-induced hypercalcemia. Other bisphosphonates may be as effective.

Antiserotonin antiemetics (ondansetron, granisetron, dolasetron) are more effective than older drugs and have few side effects. Dolasetron may cause a prolonged QT interval and therefore must be used with caution in patients at risk of ventricular arrhythmias. Expense is a major deterrent to the use of the antiserotonin antiemetics, and they lose effectiveness 48 to 72 hours after chemotherapy. Phenothiazines, benzodiazepines, and dexamethasone are more effective for delayed nausea.

Amifostine is a chemoprotectant that is beneficial in treating neurotoxicity and nephrotoxicity caused by cisplatin. Dexrazoxane is a cardioprotectant used with anthracyclines. The clinical usefulness of amifostine and dexrazoxane has not been fully defined.

Radiation therapy: This modality has become more tolerable and safer with newer technologies and improved techniques, such as high-energy linear accelerators, better control of target areas, three-dimensional CT planning, and improved dosimetry. Patients who have conditions such as arthritis, kyphoscoliosis, parkinsonism, or dementia may require special positioning or immobilization. The elderly appear to be at increased risk of radiation lung damage, coronary artery injury, esophagitis, and enteritis, necessitating precise planning and dosimetry. Mucositis, esophagitis, or enteritis may lead to more rapid dehydration in the elderly. Despite these problems, some seemingly frail elderly patients can tolerate radiation therapy.

Pain control: Pain control is especially important in the care of elderly cancer patients. Although pain control is often considered part of end-of-life care, persons with cancer may have chronic pain or intermittently painful complications of cancer during any stage of their disease and it may continue over the course of many years. The goal is to achieve an acceptable level of pain control with tolerable adverse effects. Comfort must be emphasized and the patient reassured that pain will be aggressively managed. Treating the source of pain is important. Radiation therapy to painful bony or other lesions should be considered. Chemotherapy may be of palliative benefit.

Opioids are used to treat severe pain not relieved by NSAIDs. Addiction should not be an issue for prescribers, and patients should be reassured that fear of addiction should not affect their use of the drug. Timed-release morphine and oxycodone as well as transdermal fentanyl relieve baseline pain. Fast-acting drugs, such as hydrocodone, oxycodone, morphine, hydromorphone, and transmucosal fentanyl lollipops, relieve intermittent or breakthrough pain. Fentanyl clearance is decreased in the elderly. Methadone, meperidine, pentazocine, and propoxyphene should not be used in the elderly. Stimulant laxatives are essential for an elderly patient receiving opioid therapy.

Elderly patients may become somnolent while being treated with opioids. Methylphenidate, taken periodically at a dose of 5 to 10 mg, is often useful, especially for those patients desiring more social interaction when taking opioids.

Pain not relieved by opioids requires adjunctive treatment. Antidepressants, anticonvulsants, or antiarrhythmics may be used for neuropathic pain. Epidural or intrathecal opioids or clonidine infusion may be extremely effective without causing side effects. Nerve blocks may be helpful for intra-abdominal or dermatomal distribution pain.

Pamidronate given intravenously monthly is effective at reducing bone pain in metastatic breast cancer, multiple myeloma, and probably prostate cancer. Radioactive strontium or samarium localizes in blastic bone metastases and reduces bone pain, but results have been less promising than first expected.

Nursing Issues

Oncology nursing is now a specialization of nursing. Oncology nurses educate and counsel patients and their families as well as administer chemotherapy, interpret and manage treatment-related side effects, coordinate community and medical services, and provide palliative care. Triage and initial management of problems in elderly cancer patients are often handled by nursing personnel with the use of standard protocols. The nurse must be able to recognize the altered presentations of illness and side effects in the elderly as well as pharmacologic differences in the use of commonly prescribed drugs. Examples of enhanced side effects of drugs used in the elderly include increased risk of disorientation, light-headedness or falls from the use of antiemetics or opioids, and increased risk of dehydration from drugs that cause vomiting and diarrhea in elderly patients with decreased thirst response. The oncology nurse is a key provider in assessing and managing pain because of the prolonged contact with patients in a variety of settings. The oncology nurse is also on the front lines of managing nutritional support and other symptoms.

Social Issues

Many social issues arise in the care of elderly cancer patients. These issues often become complex and require the expertise of a social worker or an interdisciplinary team. Services may have to be coordinated to help with home care, travel, meal preparation, and drug adherence. Counseling may be warranted to help patients and their families cope with the seriousness of the illness. Efforts to overcome these difficulties frequently require alterations in treatment plans and interdisciplinary approaches.

Finances may pose problems as well. Oral chemotherapy drugs are covered 80% by Medicare if there is also an approved IV form of the drug. Other drugs taken orally, including pain medications (especially timed-release formulations), can be very expensive and are not covered by Medicare. Most pharmaceutical companies have indigent patient programs.

End-of-Life Issues

It must not be forgotten that cancer is often fatal. Sometimes treatment becomes futile, exposing an elderly patient to suffering that outweighs any potential benefit. Even at the time of initial diagnosis, treatment is not always warranted. An honest discussion of what is likely to be gained and what the side effects of treatment are likely to be is the best course of action. Most patients understand when it is time to make a transition to more palliative goals of care (palliative care is defined by the World Health Organization as the active total care of patients whose disease is not responsive to treatment). This understanding can be fostered by direct and forthright discussions regarding prognosis and benefits and risks of therapy and is enhanced by a trusting physician-patient relationship.

Involvement of hospice services early in the course of palliative care can be helpful. The financial benefits alone of switching to the Medicare hospice benefit may be substantial. Hospice personnel have expertise in preparing patients and families spiritually, financially, and legally for the end of life.

Most patients wish to remain at home. Every effort should be made to accommodate this wish, but attention needs to be paid to caregiver burden. Short stays in a hospital or nursing home, which are covered by Medicare, may be necessary for respite to caregivers. Interventions and clinic visits should be kept to the minimum necessary for palliation. Although Medicare reimburses physicians for time spent on hospice issues, the reimbursement is rarely adequate and does not compensate for the amount of documentation required.