Margot A. Gosney
Geriatric Oncology
Cancer is a major cause of death and morbidity in older adults. In England and Wales, more than 331,000 people were diagnosed with cancer in 2011, and there were over 162,000 cancer deaths in 2012; of these, 52% were 75 years of age or older.1 Female death rates from lung cancer have increased, whereas female mortality for breast and bowel cancer are the lowest they have been in 40 years. Unlike women, male mortality rates for lung cancer have fallen to their lowest levels in 40 years, and this has also been seen in bowel cancer. Men are 36% more likely than women to die from cancer, and mortality rates in the United Kingdom have decreased by more 24% since the mid-1980s. Improvements in treatment, early diagnosis, and public awareness are the main reasons for this progress. In the United Kingdom, it has been estimated that cancer costs over £15 billion/year; this figure includes £17.6 billion in economic costs, £5.6 billion for health, and £21.6 billion for unpaid care.2 In 2011, it was announced that an excess of 14,000 cancer deaths/year is seen in the U.K. population aged 70 years and older.3,4
The full impact of cancer in older people is unclear if poor histologic verification occurs. Although this was a common occurrence 20 years ago, now only 6% men and 7% of women die of an unknown primary.1 In the United States and in Europe, specialized groups have been formed to focus attention on geriatric oncology, such as the International Society for Geriatric Oncology (SIOG; http://siog.org) and European Society of Medical Oncology (ESMO; http://www.esmo.org).
Cancer and Aging
Older adults are more likely to develop cancer, and differences in tumor growth and spread occur as a result of aging. The relationship between cancer and aging is complex, and various factors, including changes in host tumor defenses and exposure to carcinogens, have roles to play in the autology of tumors.5 Current theories of cancer causation in older adults include decreased ability to repair DNA, oncogene activation or amplification, tumor suppressor gene loss, decreased immune surveillance, prolonged duration of carcinogenic exposure, and increased susceptibility of aged cells to carcinogens.
There is debate as to whether carcinogenesis and aging are related phenomena. Many state that such a relationship exists,6,7 with some postulating that cancer develops as a consequence of normal aging processes, although others favor common causative factors for cancer and aging.8 There is a relationship between chromosomal alterations and malignancy.9 Several inherited disorders featuring chromosomal breakage and an increased frequency of malignant disease show abnormalities of DNA repair or recombination,10 and many genetically determined syndromes have an accelerated progression of biologic aging and high frequency of malignant disease.
The increased incidence of cancer with age can be interpreted by the two major theories of aging. The first, the damage, or error, theory holds that over time, there is an accumulation of damage to vital areas of cellular or organ function, which culminates in the manifestations of the aging process. Mutations may occur in certain key genes or in many individual genes on a random basis. The multistep model of carcinogenesis fits with this theory because successive cancer-causing mutations accumulate during the aging process. The alternative, or program, theory considers aging as a later stage of a program that proceeds throughout embryogenesis to growth development and maturation. During aging, certain genes become expressed, and others are shut down.
The response of the body to a cancer is not a unique mechanism. There has been much interest in circulating concentrations of insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) and their association with an increased risk of common cancers. Although these associations are modest, and vary among sites, further clarification is required,11–13
There is conflicting opinion regarding the growth and spread of cancer in older patients. Although some evidence shows death to be earlier in older subjects, coexisting diseases have obvious effects on morbidity and mortality. Some experimental work has demonstrated slower tumor growth, fewer metastases, and longer survival in older rodents, and others have shown decreased tumor growth associated with impaired T cell function.14 Cultures from melanoma cell lines have demonstrated that T cells from young but not old donors stimulate the growth of tumor cells, and T cells from young but not old mice produce angiogenic factors, resulting in a richer vascular supply that may be responsible for increased growth and metastases.
Many older adults have been exposed to carcinogenic agents as a result of their occupation (e.g., working with asbestos, inorganic chemicals such as arsenic or nickel, and plant products such as aflatoxin, polycyclic hydrocarbons, and dyes). The key lifestyle environmental factors in older adults are tobacco consumption and atmospheric pollution. Studies have shown an increased incidence of cancer of the endometrium and breast associated with diet, and other dietary factors such as fiber protect against the development of carcinoma of the bowel.15
The relationship between cancer and aging is clearly complex. Various factors, including exposure to carcinogens and changes in the host defense, have roles to play in the development of tumors.
Prevention
Prevention may be classified into three types.16 Primary prevention aims to prevent the onset of a disease, and secondary prevention aims to halt progression of a disease once it has been established. By identifying the disease early, often while the patient is still asymptomatic, prompt and effective treatment may be given to stop progression of the disease. Tertiary prevention aims to rehabilitate people with an established disease to minimize residual disabilities and complications. The focus of many cancer studies is primary and secondary prevention. Approximately 80% of all cancers are potentially preventable, and many public health strategies have been aimed at behavior modification.
For screening to be applicable, a disease must be common and curable if diagnosed early, and the test involved must be highly sensitive. Screening in the United Kingdom is almost exclusively for tumors of the breast, cervix, and colon. Older adults are less likely than those from younger age groups to participate in screening and cancer detection programs, which may be due to inadequate knowledge about cancer,17,18 lower educational level,19 perceived susceptibility,20 and ethnic background.21 Other factors, such as fear of cancer22 and its treatment, difficulty differentiating between normal physiologic changes and early symptoms or signs of cancer, and fatalism23 have also been implicated. Men participate less than women in screening procedures,24 although the role of ethnicity, marital status, availability of screening test, and physician attitude are all known to have effects on this gender inequality. Older adults who scored higher in a health perception questionnaire that measured current health, prior health, health outlook, health worries and concerns, resistance or susceptibility to illness, and rejection of the sick role were also more likely to have participated in cancer screening programs.25
Older adults involved in health promotion have been found to have significant improvement in their quality of life, and therefore this should be advocated.26 If the screening of older adults is to increase, the involvement of health care providers will be important.27 Many exploratory studies have found that individuals who fail to undergo cancer screening tests have cited a lack of involvement with their health care provider in the previous year; also, in some countries, there are financial implications of taking such screening tests. Agist attitudes must not prevent physicians from recommending screening, nurses must not remove a patient’s autonomy, and screening services must not exclude those most at risk. Educating health care practitioners, instilling confidence in their ability to teach certain self-examination techniques to patients and increasing the education of patients, is essential.
U.S. citizens show high enthusiasm for cancer screening,28 although participation by certain subgroups (e.g., Hispanics) is reduced.24 In the United Kingdom, many older adults have reported that they wish to continue to be actively invited for cancer screening, even though they may not all take up the offer.29
To improve the early detection of cancer, several questions, including the attitudes of older people toward screening and the barriers perceived by the patient, especially for skin, breast, and cervical cancers, need to be asked.30 The comprehensive geriatric assessment (CGA) process can be used to identify suitable candidates for cancer screening in older adults.31 The presence of a comorbid illness may reduce32 or increase33 the participation rate in cancer screening.
Breast Cancer Screening
First-line screening is through teaching breast self-examination. Studies have suggested that nurses do not view teaching breast health as part of their role in patient intervention, particularly in the acute care setting.27 A clinical breast examination does not increase the accuracy of breast screening when combined with mammography.34 Despite there being a number of clear guidelines for breast cancer screening, those most at risk still reject screening.35
The information on mammographic screening presented on various websites is not necessarily balanced. Some provide advice that is not in accord with AMA and General Medical Council guideline recommendations for informed consent. In one study, all the advocacy groups involved were receiving industry funding, apparently without restrictions, and the major harms of screening were mentioned in only a small proportion of websites.36 A number of groups, including older, low-income, and African American women, are less likely to be screened,17,23,37 as well as those with long-term limitations in their activities of daily living due to disability.38–40 Other factors may reduce a patient’s likelihood of attending screening, including male radiographers; younger women were more likely to describe embarrassment than older women, but there was a universal view that male radiographers result in a poor return for future screening appointments.41
The American Cancer Society (ACS) considers that screening decisions should be individualized and, as long as the woman is in reasonably good health and fit enough to be a candidate for treatment, she should continue to be screened with mammography. However, if the individual has a life expectancy of less than 3 to 5 years, severe functional limitations, or multiple or severe comorbidities likely to limit life expectancy, it may be appropriate to consider cessation of screening.35 Data obtained from the Surveillance, Epidemiology, and End Results (SEER) program has shown a life extension of 178 days for those older than 85 years and 617 days for those aged 65 to 69 years42 if screening was extended.
Colorectal Cancer Screening
Unfortunately, despite well-documented evidence of the benefits of screening for colorectal cancer (CRC), there is a relatively low participation rate, particularly when comparing the screening programs that exist for breast or cervical cancer.43 In 1996, Hardcastle and colleagues published the results of a 10-year U.K. study that collected fecal occult blood from over 152,000 people aged 45 to 72 years. They found that 360 people had died from colorectal cancer in the screened group compared with 420 in the control group, a 15% reduction in cumulative mortality in the screened group.44 At 2002 prices, the cost was £5,290/cancer detected, and the incremental cost per life year gained as a result of the screening was £1,584.45 A similar French study invited participants up to 94 years of age and found that of the 206 adenocarcinomas detected, 47.6% were stage 1 and 23.8% were stage 2.46 There are, however, a variety of time- and priority- related reasons why individuals fail to undergo fecal occult blood testing; these include the following: “did not notice test in mailbox” or “forgot,” as well as more health-related issues such as “severe illness” and “family circumstances.”47 Although much of the evidence was from younger people, a Dutch study screened individuals up to 80 years of age, when colonoscopy capacity was unlimited, and up to 75 years of age, when colonoscopy capacity was decreased. They found that increasing the colonoscopy capacity substantially increased health benefits.48 Worldwide, the age for screening is variable (lower age limit, 50 years, to upper age limit, 74 years). Although improved adherence with fecal occult blood testing is associated with being female, younger, and more educated, recommendation by a physician increases compliance,19 as does the design of instructions.49
The U.K. National Screening Committee (UKNSC) currently offers screening every 2 years to all men and women aged 60 to 74 years. Although individuals older than 74 years can request a kit, they are not sent one automatically. In certain areas of the United Kingdom, starting in December 2016, all men and women 55 years of age will be asked to undergo sigmoidoscopy; this will affect older groups in the future. Controversy exists over the previous upper age limit of 69 years, but the suggestion by Hardcastle and associates44 and Kronborg50 of an upper age limit of 74 years has been accepted. It is expected that for every 100 patients screened, 98% will receive a normal result and be returned to routine screening, and the remaining 2% will be offered a colonoscopy. For every 20 individuals offered colonoscopy, 16 will accept the invitation and, of them, 50% are likely to have nothing abnormal detected, 38% are likely to have one or more polyps detected, and 12% are likely to have colorectal cancer detected.51
The 5-year risk of colorectal cancer after a negative screening colonoscopy is extremely low—1.3% of advanced adenomas detected approximately 5 years after a negative colonoscopy,52 although higher in some series.53 The role of screening colonoscopy in very old patients is a balance between increased prevalence of neoplasia (26.5% in the 75- to 79-year-old group vs. 28.6% in those aged 80 years or older) versus life expectancy in the two different age groups. Screening colonoscopy in those aged 80 years and older results in only 15% of the expected gain in life expectancy seen in younger patients; this should therefore only be performed after careful consideration of potential benefits, risks, and patient preferences.54
Although colonoscopy is relatively safe in older adults, the process is not without morbidity and, in rare cases, mortality. Increasing age increases the risks of poor bowel preparation and failed procedures. However, older patients can prove to be more tolerant than younger patients during the procedure and can undergo colonoscopy without sedation because the individual’s pain threshold is not exceeded. With an entire bowel-cleansing preparation, there can be a 71.5% completion rate in older people.55 Older adults who have not had a previous colonoscopy have higher baseline anxiety scores, but informational videos can reduce anxiety, as can more education about the purpose of the procedure, procedural details, and knowledge of potential complications.56 Local data from several countries have demonstrated that colonoscopy in the very old can be safe and worthwhile.57 The U.K. flexible sigmoidoscopy screening trial investigators found that a one-time flexible sigmoidoscopy was an acceptable, feasible, and safe screening regimen. This relatively simple procedure was carried out on almost 50 people/week, with two or three colonoscopy referrals being generated per center. The control group was not screened, and therefore comparisons could not be undertaken.58 The limitations of bowel preparation and depth of insertion of the sigmoidoscope clearly affects the yield.59
Computed tomography (CT) colonography takes approximately 10 to 15 minutes, and the accuracy is similar to that of conventional colonoscopy.60 It is, however, more expensive,61 and is influenced by the experience of those reporting the scan.62 It is good for identifying polyps that may be missed on colonoscopy,63 may identify extracolonic abnormalities,64 and requires minimal preparation, which may be of particular benefit for older adults.65
Investigating the older frail patient with lower bowel symptoms is difficult. It may result in up to 25% of flexible sigmoidoscopies being unsatisfactory due to poor bowel preparation.
Prostate Cancer Screening
There has been much controversy about the benefits of prostate cancer screening. The American Cancer Society and American Urological Association recommend annual prostate-specific antigen (PSA) screening for average-risk men aged 50 years and older if they have more than a 10-year life expectancy.66 However, there is not yet evidence of overall mortality benefit from PSA screening.67
Lung Cancer Screening
The use of a baseline radiograph for lung cancer detection was investigated in the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. This study, of almost 155,000 participants, included individuals up to the age of 74 years. In the initial screening, approximately 9% of radiographs were suspicious for lung cancer, and these rates were highest for older age groups and for smokers.68 The U.S. National Lung Cancer Screening trial found that cancer mortality was reduced by 20%. In an Italian study of older patients (mean age, 58 years), some of whom were up to the age of 84 years, there was little evidence of benefit for the routine use of screening.69 Other lung screening trials have adopted low-dose CT (LDCT) and included individuals up to the age of 74 years who had a smoking history or were current smokers.69,70
Cancer Incidence
De Rijke and colleagues have used high-quality data from the Netherlands and reported that total cancer incidence rates in men and women were highest in the 85- to 94-year-old age group.71 In middle-aged groups, there was a stable rate of the most common tumors, but increasing rates in the oldest age groups. Although it was speculated that this might be due to an increase as a result of a decrease in mortality from other diseases, they also suggested that it might be related to an artifactual increase resulting from increased cancer detection rates in those in the very old group. With increasing interest in older patients with malignant disease, the latter rather than the former seems more likely.
Although age-specific rates and age-adjusted rates can be calculated for major cancers using incidence data at different cancer registries, there is a disconnect between cancer mortality in Europe and the US. However, trends are favorable although not consistent across all age groups.72,73
Assessment
The CGA is widely used internationally, and the results are used to modify treatment based on the extent of frailty.74–79 A 2015 Cochrane systematic review of a mixed population of patients has reported that although there were limitations within the meta-analysis, there was evidence that patients who had undergone a CGA were more likely to be alive and in their own home following admission to hospital.80
CGA is essential in the management of older patients with cancer. There are, however, different views on whether a complete CGA is required. Overcash and colleagues, in 2005 and 2006, reported that a 15-item abbreviated CGA could be used to identify older adults presenting with cancer who would benefit from the entire CGA process.81,82 They identified that four domains—functional status, instrumental activities of daily living, depression (using the geriatric depression scale), and cognition (using the Mini Mental State Examination [MMSE])—should be scored separately. Any score suggestive of deficits in these areas should be a marker for an in-depth assessment. In a pilot study, a mini geriatric assessment (MGA) administered by a gastroenterologist was used during decision making by a multidisciplinary cancer team. They found that the concordance between the MGA and CGA was good for the assessment of cognitive function, psychological status, and functional status but less accurate for nutritional status and comorbidity.
The Vulnerable Elders Survey-13 (VES-13) is an instrument to identify vulnerable older people in the community.83 It has been used to predict functional decline and survival in different cancer types.84 In older patients with cancer, the VES is highly predictive of impaired functional status and is a preliminary means of assessing older adults before undertaking a full CGA.85 Higher VES-13 scores are linked with an increased probability of not completing radiotherapy for a variety of different tumor types.86 The VES-13 has performed almost as well as a conventional CGA in detecting geriatric impairments in populations of older men with prostate cancer receiving androgen ablation87 and, in other patients with several different tumor types, VES-13 is a useful predictor for survival.
Postal screening questionnaires (surveys) have been used in geriatric medicine since the 1980s,88 and there has been interest in postal questionnaires and computer-based, self-administered questionnaires for older patients with cancer.89–91 Although this screening identifies some potential issues, patients probably benefit from broader, more in-depth clinical assessment, and the high support needs of patients were often identified only in follow-up telephone calls.
For patients with cancer admitted for surgery, there is some evidence for embedding a CGA geriatric assessment service.92 However, only one third of geriatricians responding to a British Geriatrics Society survey identified that their hospital provided some geriatric medicine input to older general surgical patients. Only 20% delivered care postoperatively; barriers to input were work force issues, lack of interspecialty collaboration, and funding.93
Comorbidity is particularly prevalent in older patients with cancer. However, cancer may be more likely to be diagnosed in healthier older patients due to primary care professionals being more reluctant to refer patients with cancer and poor general health.94 Older adults with cancer experience a high number of concurrent symptoms (3 to 18), and there is a growing body of literature that describes specific symptom clusters in such patients. Unfortunately many symptoms may be attributed to the cancer and the so-called giants of geriatric medicine, such as urinary and fecal incontinence, fatigue, and frailty.95 In 1987, Charleson and associates developed a method of classifying prognostic comorbidity using longitudinal studies. This index has been widely implemented into daily practice.96 Predictably, increasing age and comorbidity are prognostic factors,97 but comorbidity and functional status are independent prognostic factors in older cancer patients.98 In the year following diagnosis, functional status in patients with all tumors, especially lung and colon, and with the exception of prostate, decline. The decrease in functional status is independent of cancer diagnosis but comorbidities, as well as age, smoking, and obesity, are clear predictors.99,100 Age is associated with increasing comorbidity in older cancer patients,101 and age-matched patients without cancer have fewer comorbidities.102 Many comorbidity indexes use retrospective financial data,103 but it is important that comorbidity be assessed prospectively, especially if it is being used during treatment decisions in multidisciplinary cancer team meetings.104 Comorbidity indices may predict short-term outcomes,104 patients who can undergo curative treatment, and overall survival rates.105
Although there are clear roles for a GGA in most cancer types, it is unclear from the many reports as to which intervention occurred following the assessment. It may, therefore, be the intervention that affects outcomes rather than the underlying issues that are identified through the CGA process. However, a CGA is strongly predictive of hospital readmission in older adults with cancer,106 survival,107,108 and treatment-related toxicity.109–111 The CGA may be used to tailor therapy to optimize patients prior to surgical management112–115 and help make a final therapeutic decision.116
In breast cancer patients, a CGA has been used to measure comorbidity retrospectively using Medicare claims.117 CGA used prospectively has identified an average of six initial problems, with a further three problems identified during follow-up.118 The most important questions that the CGA might be able to answer include the following119:
• Which older women should be screened for breast cancer?
• What is the best first-line treatment?
• Which older women require adjuvant radiotherapy?
• Which older women should receive adjuvant chemotherapy, if indicated by tumor?
• Which chemotherapy is appropriate for older women using a palliative approach?
Although the CGA is associated with improved outcome in older patients, the data so far have suggested that further work, including a randomized controlled trial, may be necessary to answer many of these questions. It must be used to support and improve therapy decisions rather than simply to prevent older women from receiving definitive treatment. Patients with more comorbidity identified by CGA at diagnosis were significantly less likely to have had surgical treatment 6 weeks later, but this may be appropriate.120
The primary care process should ensure that frailty and/or comorbidity are reliable detected in older patients.121 Systematic reviews have identified the high prevalence of frailty in older adults with cancer and its effect on outcomes.122,123 Therefore, quantitative and qualitative outcome measures cannot be considered without appropriate adjustment for frailty.124–127 Some frailty tools identify frailty more accurately, so only well-validated tools should be selected.128 Identification of frailty may help predict a higher risk of hospitalization or primary care usage, although this has yet to be proven definitively.129
Diagnosis and Stage of Disease
Diagnosis
For many patients, early diagnosis is the key to improved survival. There is evidence that the stage of disease varies in older adults at presentation. For those with breast cancer, it has been found to be an earlier stage when screening is used. The proportion of cancer cases diagnosed and confirmed by mammography in older women appears to be increasing.130 However, many older patients delay seeking medical advice, which may result in cancer being diagnosed at a more advanced stage.
There is controversy as to whether the patient’s age alone influences the method and thoroughness of a diagnostic investigation. Significantly more older patients with colorectal cancer present as emergency cases with advanced disease when compared with younger patients. These emergency cases are often not referred to surgical units, which may be partly explained by an atypical presentation, general frailty, or the patient being unsuitable for surgery. Geriatricians are experienced in assessing preexisting disability and concurrent disease and understanding functional status, level of dependency, and psychological adjustment. This enables joint decisions to be made with regard to further therapy before rehabilitation and, it is hoped, recovery of the older patient with cancer.131
With improved screening and diagnostic tests, older patients should present with an earlier stage of cancer. The knowledge of and ability to treat comorbidity should ensure that older patients are just as likely to be investigated as their younger counterparts. This should be particularly encouraged in patients with tumors for whom low-risk elective surgery can be undertaken and has been found to have similar morbidity and mortality in all age groups.132
Stage of Disease
Cancer staging is an important component of management, and histology and clinical stage of the cancer are independent predictors of survival.133 There is a clear relationship between age and stage at diagnosis and between age at diagnosis and treatment received by the patient with cancer, although this difference is diminishing.134
Treatment
Older patients should now be receiving therapy comparable to that of their younger counterparts, although historically this may not always have been the case. In the 1980s and 1990s, older adults with cancer were less likely to receive definitive treatment than younger patients. Currently, there are few patients who, following assessment of comorbidity, should not be considered for active curative treatment. There is, however, an issue regarding the inclusion of older adults in clinical trials. U.S. data comparing 1996 to 1998 with 2000 to 2002 showed an increase in the total number of trial participants, with only 1.3% of 65- to-74-year-old patients and 0.5% of patients older than 75 years being represented. With increasing age, study participation becomes reduced.135 There has been an underrepresentation of women and black and ethnic minority groups in clinical trials; the underrepresentation of patients older than 65 years was documented even in 1999.136 At this time, many trials explicitly excluded older adults but, even in studies in which recruitment of older individuals was attempted, there was still underrepresentation in regard to breast cancer treatment and, to a lesser extent, for other tumor types.136 White patients in suburban areas, and those who were uninsured, had better, although not representative, recruitment in older age groups.137 These findings are not exclusive to the United States or United Kingdom.138,139 The reasons given by newly diagnosed patients were “feeling too anxious” (40%), “not interested” (25%), “no time” (12.5%), “too sick” (5%), or “too healthy” (5%) to be included in clinical trials.140
Some have argued that older patients are more likely to suffer from toxicity with chemotherapy, although newer drugs have reduced toxicity and allow good palliation for most cancers.141 Younger patients often report more nausea, fatigue, and vomiting than their older counterparts and therefore these side effects should not overtly restrict the recruitment of older adults.142 Other reasons given for the nontreatment of older adults with cancer have included advanced disease at presentation. Although there is some evidence that patients older than 55 years have more advanced disease at presentation, this is not a universal finding.134,143,144
Some physicians responsible for older patients with cancer believe that they are less likely to want treatment than their younger counterparts.144a This was not the finding of Yellen and colleagues, who used structured scenarios to assess patients’ willingness to accept toxic chemotherapy to enhance survival. They reported that older patients were as willing to choose chemotherapy as younger patients, although the former required a greater survival advantage before they would choose a toxic regimen over a less toxic alternative.
Myths about cancer may affect treatment. If older patients believe that a cancer treatment is worse than the disease itself, or if they have a greater fear of cancer than younger patients,145 they may decline treatment. If adequate information is given to older patients, they are likely to accept treatment in a similar fashion to younger patients146,147 and may experience less emotional distress following the diagnosis of cancer. Bilodeau and Degner have found that older women with breast cancer prefer to assume a passive role in treatment decision making.148 Whereas most younger women thought that the stage of disease, likelihood of cure, and treatment options were the most important aspects of the information they received, older women considered that self-care issues were more important.148,149
The attitudes of physicians with regard to informing older adults about a cancer diagnosis may also influence the treatment that they receive. Although there is a widely held view that older adults do not wish to be informed about a new cancer diagnosis, 80% of respondents aged 65 to 94 years wanted to be informed of a cancer diagnosis, with 70% of respondents also wanting their relatives to be informed when the diagnosis was made.150 This is in contrast to how relatives of cancer patients feel, for whom 6% did not want the diagnosis to be disclosed.151 It must, however, be remembered that collusion with relatives and nondisclosure to patients have a negative effect on those caring for the patient.152
There are three categories of decision making roles about treatment—preferred, actual, and perceived roles. There is often a mismatch between patients’ preferred and actual roles and, although this occurs in patients of all ages, it must be carefully avoided when dealing with older patients about to begin cancer treatment.153 The communication skills required to deliver cancer care have been defined following a number of consensus meetings.154
The need for information and support when viewed through the eyes of patients, relatives, and professionals is often different. Patient education should therefore be tailored to reflect older patients’ information support needs and abilities, rather than using generic materials.155 Patient preferences can be assessed using a patient-driven questionnaire,156 and their satisfaction can be measured through questionnaires administered via paper or the Internet.157 Although why older adults with cancer accept or decline prime treatment varies considerably when systematically studied,158 this is also consistent with other evidence on nonadherence.159 Overall, many older cancer patients prefer to receive less information about their illness and treatment and assume a less active role in making treatment decisions.160 Therefore, communication to patients about cancer must improve.161 At the end of treatment, if decisions to limit treatment are made, many relatives support patients in voicing their preferences, but one third may act against the known or presumed wishes of the patient.162 Therefore, although relatives play some role in end-of-life decision making and treatment decisions, physicians must guard against relatives voicing different decisions than those expressed by the patient.
Surgery
Surgery is considered to be the treatment of choice for most cancers, and patients should not be denied surgery on the basis of chronologic age. Nonetheless, mortality and morbidity rates are often increased in older patients who undergo cancer surgery. Multidisciplinary care and teamwork can, however, minimize mortality and morbidity.163
Advanced age per se is often used by the patient’s family or health care professional to justify not proceeding with surgery. However, this agist attitude has fortunately been declining. Surgery for octogenarians now results in better clinical outcomes for cancer and noncancer patients. Even octogenarians can undergo high-risk cancer surgery, such as pancreatectomy, esophagectomy, and lung cancer resection, for which survival is again associated with preoperative comorbidities.164 A number of guidelines exist for the management of perioperative patients undergoing noncardiac surgery,165 and even older patients should be considered for surgical resection of metastatic cancer.166 The POSSUM score (Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity) was devised from retrospective and prospective data.167 Both APACHE II and POSSUM scores reliably predict perioperative complications and mortality in patients with different types of cancers who undergo surgery.168,169 Preoperative assessment of any older surgical patient is essential, particularly to identify those most at risk of postoperative cognitive dysfunction (POCD).170
Drug Therapy
The normal physiologic changes of aging affect drug absorption, distribution, metabolism, and elimination. Older patients with cancer may receive a wide range of drugs, including chemotherapeutic agents, analgesics, antiemetics, and antibiotics in addition to drug therapy that had been previously prescribed for coexisting medical disorders.
Some normal changes of aging can affect drug absorption. Oral drugs are modified by gastric motility and emptying time, whereas the absorption of parenterally administered drugs is dependent on local blood flow in muscles and fatty tissue. Drug distribution is affected by the decrease in total body water and albumin and change in the ratio of lean body weight to fat. The reduction in the albumin level results in a greater concentration of unbound, highly lipophilic drugs in the circulation that can exert their effects.
Drug metabolism is affected by decreased liver mass and hepatic blood flow, as well as decreased microsomal enzymatic activity in the liver. Elimination is affected by a reduction in the glomerular filtration rate, decreased renal blood flow, and renal tubular function and is particularly important with cyclophosphamide and methotrexate, which are both excreted renally.
Unfortunately, as with younger patients with cancer, many older adults with cancer may be taking multiple medications, which will increase the risk of adverse drug reactions, drug-drug interactions, and nonadherence. Many clinical trials do little to include typical older patients with frailty. As a result, progress in the understanding of many of the pharmacologic issues when treating older individuals with cancer has yet to be fully addressed.171
Chemotherapy
Older patients are less likely to receive chemotherapy and, if treated, it is more likely to be outside a clinical trial, although this is gradually improving. All drug therapy in older adults is affected by their altered pharmacokinetics and pharmacodynamics, and some chemotherapeutic agents pose special problems.172 Reduction of chemotherapeutic drug dosages may reduce toxicity at the expense of response rates, lower response rates without any effect on toxicity, or result in better tolerance, but provide no survival advantage. Reducing dosages on the basis of age alone is not justified.
A prospective pilot study by Chen and coworkers has found that although older patients undergoing chemotherapy experience some toxicity, they could generally tolerate it with limited impact on their independence, other comorbidities, and quality of life.173 This, however, is in contrast to the views of Repetto,174 who considered that age was such a clear risk factor for chemotherapy-induced neutropenia and its complications, particularly in the treatment of lymphoma or solid tumors, that without the use of colony-stimulating factors better outcomes would not be achieved.
The use of erythropoietin to treat anemia175 may not be without risks.176 Chemotherapy- induced anemia may also be treated with darbepoetin alfa.177 The pharmacology and polypharmacy associated with the older cancer patient has been extensively reviewed by Lichtman and Boparai,178,179 and others have highlighted the risks of concomitant medication and potential drug interactions.180–182 Complications such as renal insufficiency,183 febrile neutropenia,184 and chemotherapy-induced alopecia185 are similar to those seen in the younger population. Anticancer therapy must be targeted using evidence from older and younger individuals186 and, when new drugs are developed, they must be evaluated in older adults, who are now becoming the main recipients of oncology drugs.187 ESMO, in 2013, presented a position paper on the current and future roles of medical oncologists but failed to mention their role in the older cancer patient.188 There is clear evidence of a disparity in race, gender, and age when considering recruitment to clinical trials,135 and evidence has suggested that education may reduce this barrier.189 Although evidence is essential for the treatment of older patients, the ACTION trial attempted to randomize woman older than 70 years to investigate the effects of adjuvant chemotherapy.190 The trial was terminated after 10 months when only four patients had been randomized. Despite widespread support, including input from patient groups, the trial failed to recruit due to the inability to convince older patients to accept randomization.190
It may be appropriate for frail patients to receive chemotherapy dose reductions, so-called older adult–friendly chemotherapy regimens, but higher rates of premature withdrawal and early deaths may still occur compared to nonfrail patients. Patients with frailty may have a shorter survival, but this may be related to frailty rather than to chemotherapy or other treatments; therefore, clinical trials that recruit frail older cancer patients are urgently needed.191
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