Position PaperEORTC elderly task force position paper: Approach to the older cancer patient
Introduction
As a result of an increasing life expectancy, the incidence of cancer cases diagnosed in the older population is rising. Indeed, cancer incidence is 11-fold higher in persons over the age of 65 than in younger ones.1 Approximately 60% of all cancers and 70% of cancer mortality occur in people older than 65 years.1 Despite this rapid increase in cancer incidence and cancer-related mortality with age, our knowledge about ageing and cancer and about optimal treatment for older cancer patients is still far from adequate.
The purpose of this paper is to focus on the influence of age on cancer presentation and cancer management in elderly cancer patients and to provide suggestions on clinical trial development and methodology in this population.
Section snippets
Definition of ‘old’
The cut-off point at which an adult is considered ‘old’ has not been well defined. Ageing is a highly individualised process and all the changes involved in this process cannot be predicted solely on the basis of chronological age. Thus, it is clear that there is an emerging need for developing tools to better evaluate a patient’s ‘functional age’ rather than chronological age.
An important question is why we have to define the term ‘older’. In the oncology field where anti-cancer treatments are
Biological markers of ageing
A possible approach is to try to assess homeostatic reserve through biochemical markers.6 Inflammation markers are considered as a predictive tool for frailty and mortality in the elderly.7 Some studies found that the ‘frailty’ phenotype in aged individuals is associated with pathologic laboratory markers, such as interleukin-6 (IL-6).8 However, IL-6 may be elevated in several inflammatory conditions and is non-specific. In addition, other studies have demonstrated that with increasing patient
Under-representation of older patients in cancer clinical trials
Despite the high frequency of cancer in the elderly population, elderly patients are frequently under-represented in clinical trials evaluating new cancer treatments.16, 17, 18 Indeed, statistically significant under-representation of the elderly was noted in registration trials for all cancer treatments except for breast cancer hormonal therapies, and this under-representation was more pronounced for patients 70 years or older.19 A Southwest Oncology Group (SWOG) analysis reported that the
Is cancer prognosis different in the older
The physical history and prognosis of some neoplasms may change with patient’s age. Acute myeloid leukaemia23 and non-Hodgkin’s lymphoma24 are associated with poor prognosis in elderly patients. In the case of breast cancer advancing age is associated with more favourable tumour biology (the prevalence of well-differentiated, hormone-receptor positive, HER-2 negative tumours is higher in the older).25, 26 On the other hand the incidence of positive lymph nodes is higher in older breast cancer
How to effectively select elderly cancer patients suitable for treatment; the role of geriatric assessment
In routine clinical practice, the major issue of the older population is heterogeneity. Some older patients will tolerate chemotherapy as well as their younger counterparts, while others will experience severe toxicity, requiring treatment reduction, treatment delay or permanent discontinuation. Thus, a major issue confronted by oncologists treating older cancer patients is how to effectively select patients suitable for standard or attenuated therapy. This is mainly relevant for treatments
Cytotoxic chemotherapy and toxicity in older cancer patients
Ageing is associated with several physiologic changes in organ function that could alter drug pharmacokinetics and have an impact on cytotoxic chemotherapy tolerability and toxicity.53 Renal function, as indicated by the glomerular filtration rate, is reduced with age.54 The decline in renal function affects the excretion of drugs whose main route of elimination is the kidney, such as platinum derivatives and methotrexate. Serum creatinine alone is insufficient as a method of renal function
Comorbidities
Multiple comorbid diseases are common in elderly cancer patients. A thorough assessment of comorbidities in cancer patients is required because it will determine the patients’ life expectancy (i.e. more immediate medical problem could end the patient’s life before the cancer itself becomes life-threatening). The overall burden of comorbidity has a negative impact on patient’s survival78, 79 and on the patient’s ability to tolerate treatment or may be a contraindication for cancer treatment
Geriatric syndromes
Additional important issues regarding the treatment of elderly cancer patients are the presence of geriatric syndromes (dementia, delirium, depression, falls, neglect and abuse, spontaneous bone fractures and failure to thrive), the level of social support provided and the nutritional status of the elderly patient. Presence of dementia has been reported as a negative prognostic factor for survival85, 86 and absence of adequate social support has been reported as a predictor of mortality in the
Outcome measures for clinical trials
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Overall Survival (OS): The ‘gold standard’ of outcome measurement in cancer clinical trials is overall survival. However, this may not be the most appropriate outcome for elderly patients treated for cancer, especially for cancers with an indolent course89 or in cases of patients with significant comorbidities which have been associated with decreased life expectancy and negative impact on cancer treatment outcome.90, 91 As older patients are likely to die from other causes than cancer,92 the
EORTC elderly task force suggestions/considerations for cancer clinical trials in older patients
Heterogeneity in elderly patients is a major issue in clinical research. In past clinical trials, data collected on elderly patients were quite sparse as age above 70 years old was often an exclusion criterion. Therefore extrapolation of results of many clinical trials to the older population is questionable.
Suggestions to improve the organisation of the clinical and research activity of geriatric oncology
The indications and suggestions of this EORTC Task Force could be better implemented and applied if a specific activity for neoplasia in the elderly could be organised in the main hospitals and oncological institutions.
Specific activities for cancer in the elderly worldwide (mainly in USA and Europe) are currently carried out in some medical oncology departments of general hospitals but also in some cancer institutes, as well as, but to a minor extent, in geriatric departments.110
A document to
Conclusion
As world population ages, cancer in the older individuals becomes a significant health problem because the incidence of most cancer types increases with age. Despite this high incidence, there is a lack of elderly-specific clinical trials. These trials are necessary in order to develop evidence-based clinical recommendations for this specific population.
A number of important questions regarding elderly cancer patients remain to be answered and should be the areas of future research.
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Development
Conflict of interest statement
None declared.
Acknowledgement
This research project and publication was supported by Fonds Cancer (FOCA) from Belgium.
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