Life expectancy, comorbidity and quality of life: the treatment equation in the older cancer patients

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1 Critical Reviews in Oncology/Hematology 37 (2001) Life expectancy, comorbidity and quality of life: the treatment equation in the older cancer patients L. Repetto *, D. Comandini, S. Mammoliti Di isione di Oncologia Medica 1, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, Geno a, Italy Accepted 17 July 2000 Contents 1. Introduction Life expectancy and comorbidity Quality of life Choice of instruments Quality of life and the choice of cancer treatment Breast cancer Prostate cancer Colorectal cancer Lung cancer Conclusion Reviewers References Biography Abstract With ageing, function preservation and maintenance of quality of life represent a major goal in an increasing proportion of patients. Life expectancy is a function of age, comorbidity, disability and cancer type and stage. Decision-making involves a delicate balance among all these factors, evaluation of treatment related complications of the overall effects of cancer and cancer treatment on the patients quality of life. Despite several instruments for the assessment of quality of life being validated, none have been calibrated to the special requirements of the older patients. The structured interview administered by a trained clinician represents a standard approach for geriatric research and even for clinical practice because of the frailty of the older population. The combination of this approach with the self-administered questionnaire appears the most effective way to minimise missing data in collecting information for patients unable to complete the form Elsevier Science Ireland Ltd. All rights reserved. Keywords: Life expectancy; Comorbidity; Quality of life; Elderly cancer patient * Corresponding author. Tel.: ; fax: address: repetto@hp380.ist.unige.it (L. Repetto) /01/$ - see front matter 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S (00)

2 Introduction L. Repetto et al. / Critical Re iews in Oncology/Hematology 37 (2001) Life expectancy and comorbidity Cancer in the older population has assumed increasing importance in the past decade. The incidence of most malignancies increases with age: more than 50% of all new diagnoses of cancer and more than 60% of all cancer deaths occur in persons aged 65 and over. We are assisting the decline in deaths related to cardiovascular diseases, conversely cancer related deaths are still increasing and will rapidly become the most common cause of mortality among persons aged 65 and over. Despite the advances in cancer treatment over the past 20 years leading to a reduction in mortality for persons under age 50, cancer mortality for older patients has not decreased [1]. This observation reflects the scarcity of clinical trials specifically designed for the aged, the current perception of the elderly as frail and dependent individuals and the poor comprehension that older patients, their family and their physicians have of clinical research. The result is that the quality of care for elderly cancer patients is poor. In clinical practice we can consider two broad groups of patients. In the first, there are patients year old, generally healthy, and completely independent in daily care for themselves, social relations and pleasurable activities. In the second group, patients are older, with one or more disabling conditions and increasingly dependent on daily care. The first group includes elderly patients requiring specialised care not dissimilar to that given to younger subjects. The second includes patients at high risk of developing life-threatening toxicity after cancer treatment. Despite a growing interest in the clinical management of cancer in the elderly, too many patients in both groups are still receiving inadequate treatment and symptom control. It is clear that with ageing, function preservation and maintenance of quality of life represent a major goal in an increasing proportion of patients. This article focuses on the assessment of life expectancy, comorbidity and quality of life in the older cancer patients. Table 1 Life expectancy a Age (year) Male Female a Average number of years of life remaining: white race. Estimation of remaining life expectancy is of particular interest and requires special consideration in the management of older cancer patients. Most oncologists will agree that cancer diagnosis is likely to decrease life expectancy in the majority of their patients aged 60 years or less. The same consideration may not be true in older people. Life expectancy is a function of age, comorbidity, disability and cancer type and stage. Decision-making involves a delicate balance among all these factors, evaluation of treatment related complications and of the overall effects of cancer and cancer treatment on the patients quality of life. Table 1 summarises life expectancy according to age class. Current life expectancies by age class are longer in comparison with the clinician s general perception, however chronological age alone is a poor indicator of survival and should not be considered as a variable on which to base the treatment option. The prevalence of chronic comorbid conditions increases with age [2,3]. Comorbidity represents one of the most visible factors of difference between younger and older individuals, and may interfere with diagnosis and treatment of cancer. The severity of comorbidity predicts poor survival, may affect clinical presentation and mask symptoms of cancer. Also the presence of functional disability affects cancer treatment [4] and survival, and it has been reported that dependency in activity of daily living (ADL) or instrumental activity of daily living (IADL) are correlated with the risk of death [5,6]. Understanding of life expectancy in elderly cancer patients is still an evolving process; there are ongoing trials which prospectively evaluate the prognostic role of age related variables in cancer patients; the results will help the practising oncologist in the decision process. The concepts of life expectancy, disease-free life expectancy and life expectancy without functional limitation should be separated. The clinical definition and the prognostic role of these variables remain to be established. It is interesting to underline that women live about 6 years longer than men but also suffer more comorbidity and disability [7,8]. The most frequent comorbid conditions observed in a series of 363 elderly cancer patients entered in the G.I.O.Ger study are reported in Table 2. These conditions are similar to these reported by other authors. It is often difficult to distinguish comorbidity and disability from cancer and cancer treatment related effects. Few studies have been published on the importance of independent evaluations of all these variables in the older cancer patients and warrant confirmation [9 11]. In planning cancer treatment, we should consider and distinguish the effects of cancer and those of

3 L. Repetto et al. / Critical Re iews in Oncology/Hematology 37 (2001) Table 2 Distribution of the six most prevalent comorbid conditions among 363 cancer patients Tumour sites Total Males Females N % N % N % Arthrosis-arthritis Hypertension Digestive diseases Cardiac diseases Vascular diseases Genitourinary diseases Table 3 The multidimensional aspects of the quality of life construct general health conditions on life expectancy. Although age may have some effects on the natural history of cancer, the large majority of patients with metastatic cancer of the lung, colorectal, urinary bladder, pancreas, stomach and kidneys will die because of cancer progression regardless of age. For these patients comorbidity and disability do not appear to substantially affect survival [9]. In patients with metastatic breast cancer and indolent disease, the presence of severe comorbidity and disability may affect survival more than cancer itself [8]. Table 4 Dimensions of quality of life assessment To describe the impact of cancer and its treatment on patients To compare the treatment outcomes To identify benefits or toxicities of treatments To inform future trials on planning through modification of aspects which detract from quality of life More controversial are the issues about the role of adjuvant chemotherapy in older patients with breast or colorectal cancer [12]. It is not our aim to discuss the clinical options for these patients, however in the decision making process assessment of comorbidity, disability, mental status, family and social support represent important tools and should be routinely evaluated [13]. 3. Quality of life Measuring the quality of life has become increasingly important in the last two decades due to prolonged life expectancy in the general population and the high prevalence of invalidating or disabling diseases including arthritis, heart disease, cancer and HIV. There are an increasing number of clinical trials of anticancer drugs that include an assessment of quality of life [14]. Table 3 enlists some aspects of quality of life assessment.

4 150 L. Repetto et al. / Critical Re iews in Oncology/Hematology 37 (2001) Table 5 Examples of HRQL instruments used with cancer patients. Generic health status measures Sickness impact profile (SIP) RAND health insurance experiment measures Medical outcomes study (MOS) instruments Nottingham health profile Psychosocial adjustment to illness scale (PAIS) Dartmouth COOP charts Generic cancer-specific instruments Quality of life index (Spitzer) Quality of life index (Padilla and Grant) Functional living index-cancer (FLIC) European organisation for research and treatment of cancer quality of life questionnaire (EORTC-QLC) Cancer rehabilitation evaluation system (CARES) Functional assessment of cancer therapy (FACT) Cancer site-specific instruments Breast cancer chemotherapy questionnaire Linear analogue self-assessment (LASA) for breast cancer Performance parameter (Head & Neck) Site-specific modules for the FACT and the EORTC-QLQ Symptom-oriented scales Rotterdam symptom checklist Symptom distress scale (McCorkle) Memorial pain assessment card Morrow assessment of nausea and emesis (MANE) scale Although numerous publications are now available on quality of life related issues, assessment of the elderly cancer patient remains a controversial area because of uncertainty on methods of measuring, the value of quality of life analysis in the clinical management, and directions for research and application [15,16]. Table 4 reports possible endpoints of quality of life studies. Several studies have demonstrated the prognostic value of quality of life [17 20]. Assessing patient-rated quality of life could help the physician to determine whether to prescribe aggressive therapy or palliative care. There is mounting evidence that physicians regularly ignore the advanced directives or expressed wishes of patients regarding end-of-life support. O Leary et al. [21] reported no correlation when they asked patients and their relatives to evaluate patients health status. Regular evaluation of the patient quality of life over time can capture functional deterioration, which physicians poorly assess. Making a decision to treat cancer should not have worse consequences for the patient than the disease itself, at any age: the balance between care versus cure is increasingly difficult as a factor of ageing. Although there is an intuitive understanding of the meaning of the phrase quality of life, we lack a standardised definition. In oncology, the 50-year-old Karnofsky Performance Status (KPS) scale is the most widely accepted and employed measure because it is easy and brief to be administered and clearly correlates with mortality. However KPS is limited by being clinician rather than patient-rated and is focused on physical functioning rather than overall measures of quality of life [22,23]. The concept of quality of life is almost impossible to define and is related to each individual s culture, religion and personal experience. Two general definitions have been proposed: 1. Quality of life is the subjective evaluation of life as a whole [24]. 2. Quality of life refers to a patient s appraisal of and satisfaction with their current level of functioning compared to what they perceive to be possible or ideal [25]. It is clear that none of these definitions indicate how one should measure quality of life. Measurement strategies based on general satisfaction with housing, employment, income, social well being, etc., are impossible to operationalise and manage in clinical practice, moreover such comprehensive assessments are money and time consuming. A few measures, focused on dimensions of quality of life directly affected by health and/or diseases and strictly applicable to a defined group, are more useful in clinical practice. Attention to the patient s needs should be stressed and there is a growing consensus on emphasising the subjectivity of the measurement. In clinical practice quality of life means maintenance of function and symptom control. The concept of what is a good life is highly individualised. Everybody would agree that cognition and no pain are essential to quality of life, but when managing severe pain in terminally ill patients some would rather prefer to maintain cognition while other would not. Age may influence a patient s perception of quality of life. Loss of independence has a different meaning at different ages: for young patients it means almost invariably a severe trauma; older patients cope better with functional impairment. 4. Choice of instruments Numerous instruments have been validated to measure health-related quality of life (Table 5). The Spitzer scale is a global evaluation of quality of life with separate components that investigate the physical and emotional aspects [26]. This scale was largely used during the 1980s for its simplicity but is now almost completely abandoned because of the growing consensus that quality of life should be rated by the patient rather than by a physician or a nurse. Today quality of life assessment should be considered a multidimensional analysis that includes evaluation of physical and psychological functioning, disease related and treatment related symptoms, and social functioning. Although quality of life should be assessed by the patient, the structured interview administered by a

5 L. Repetto et al. / Critical Re iews in Oncology/Hematology 37 (2001) trained clinician represents a standard approach for geriatric research and even for clinical practice because of the frailty of the older population. In particular patients with visual or hearing impairment, and who cannot read or write. The interview is more costly and the type of patient interviewer interaction may bias the results, conversely self-administered questionnaires are not suitable for impaired and frail subjects. The combination of the two approaches, starting with the self-administered questionnaire and reserving the structured interview for patients unable to complete the form, appear the most effective way to minimise missing data in collecting information. The debate between using instruments that are cancer specific or generic measures is still unsolved. The cancer-specific quality of life instruments (FLIC, EORTC, FACT) have high reliability and validity, and are responsive to changes from treatments. In addition, they allow detection of toxicity and concerns related to cancer treatment. These instruments represent the best choice in the comparative evaluation of cancer treatments. Generic instruments have considerable value if one wishes to compare the general impact of differing conditions on health-related quality of life (HRQL). Considering the older cancer patients geriatric assessment tools (mental status, cognitive status, ADL, IADL) represent important additional points. However the same general principles used to define the expected impact of cancer and cancer treatment on quality of life and specific measures likely to reflect these effects should be recommended in the older patients. Assessing frail patients is the most difficult area due to lack of compliance and exclusion from clinical trials. As a consequence there is little research in this group of cancer patients. Despite several instruments for the assessment of quality of life being validated, none has been calibrated to the special requirements of the older patients. 5. Quality of life and the choice of cancer treatment 5.1. Breast cancer Breast cancer is the most common cancer in women and the majority of new diagnoses occur in older women. Despite that breast cancer is diagnosed at a more advanced stage it receives less adequate treatment and survival is poorer in older patients. There is considerable variation in the care of these patients with substantial impact on quality of life. Few patients are actually consulted when decisions are made. Older women with breast cancer appear to better adjust in the first year after surgery in comparison with younger patients [27,28] Prostate cancer Prostate cancer is the leading cancer in men. Major controversies exist on the benefit of PSA and rectal ultrasound screening with respect to mortality and quality of life. Specific quality of life issues that should be addressed in clinical trials are the psychological impact of false positive tests, the uro-genital dysfunction after radical prostatectomy or radiotherapy, and even the psychological impact of a watch and wait policy Colorectal cancer Although colorectal cancer is the second commonest form of cancer, relatively few clinical trials have studied quality of life among these patients. As a common disease affecting the elderly, colorectal cancer has largely been neglected. In the CARES studies colorectal cancer patients fared better than lung cancer but poorer than prostate cancer in many dimensions of quality of life except for specific sexual problems associated with prostate cancer [29] Lung cancer Lung cancer is the most common cancer in men and second in women. Survival is poor and the treatment quite toxic. Therefore maintenance of quality of life assumes a major role in the clinical management of those patients. Ahles et. al. [30] reported that patients with small cell lung cancer receiving both chemotherapy and radiotherapy had increased survival but also increased toxicity and psychological distress. 6. Conclusion There is an increasing interest in the quality of life evaluation in older cancer patients. With ageing quality of life assessment becomes a primary endpoint and should be incorporated in routine clinical practice. Quality of life evaluation is far from standardised. Aged patients require individualised assessments, the combination of a self-administered questionnaire and a structured interview appears the best approach. Several aspects of quality of life evaluation are controversial. When planning new therapies the value of patients subjective assessment should remain central to any consideration about treatment. Physicians and other health care providers must pay more attention to results of quality of life research in managing older cancer patients. Reviewers Dr J. Prendiville, Guy s Hospital, Guy s and St Thomas Cancer Centre, Medical Oncology, St. Thomas Street, London SE1 9RT. UK Dr M. Extermann, H. Lee Moffitt Cancer Centre & Research Institute, 12902, Dr. MAgnolia Str., Tampa, FL 33612, USA

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Quality of Life in patients with limited small-cell carcinoma of the lung receiving chemotherapy with or without radiation therapy for cancer and leukemia group B. Psychother Psychosom 1994;62: Biography Lazzaro Repetto was born in Genoa, Italy in He received an MD from Genoa University in 1982, specialising in Haematology in 1985, and a PhD in Experimental Haematology in 1991, specialising in Oncology. He has been a postdoctoral fellow at Genoa University ( ), Istituto Nazionale per la Ricerca sul Cancro ( ) and Royal Marsden Hospital, London ( ). He was Assistant Professor of the Departments of Medicine, S. Martino Hospital Genoa ( ) and Medical Oncology Istituto Nazionale per la Ricerca sul Cancro ( ), where since 1994 he has been Deputy Head. He is the author of more than 100 publications on the fields of experimental haematology, breast cancer and geriatric oncology. He is also a member of the EORTC Study Group, studying neoplasia in the elderly, the Organising Committee of the International Conference on Geriatric Oncology and is the President of the Italian Group of Geriatric Oncology (G.I.O.Ger)..