Journal of Clinical Oncology, Vol 19, Issue 4
(February), 2001: 1147-1151
© 2001 American Society for Clinical Oncology
Perspectives on Comorbidity and Cancer in Older Patients: Approaches to Expand the Knowledge Base
By Rosemary Yancik,
Patricia A. Ganz,
Claudette G. Varricchio,
Barbara Conley
From the Geriatrics Program, National Institute on Aging; Divisions of Cancer Prevention and Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD; and Division of Cancer Prevention and Control Research, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA.
Address reprint requests to Rosemary Yancik, PhD, National Institute on Aging, Geriatrics Program, Suite 3E327, 7201 Wisconsin Ave, Bethesda, MD 20892-9205; email: yancikr{at}exmur.nia.nih.gov
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ABSTRACT
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Abstract : Not only do persons 65 years and older bear a disproportionate burden of cancer, advancing age is associated with increased vulnerability to other age-related health problems. Newly diagnosed older cancer patients who have lived into later years of life may have concurrent ailments (eg, diabetes, chronic obstructive pulmonary disease, heart disease, arthritis, and/or hypertension) that could affect treatment choice, prognosis, and survival. The clinician must often make cancer treatment decisions in the context of an older individual’s pre-existing health problems (ie, comorbidity). Ways to produce reliable information on comorbidity that can be effectively used in evaluation of older cancer patients are urgently needed. What is the nature and severity of the older patient’s comorbid health problems? How do other age-related conditions influence treatment decisions and the cancer course? How do already compromised older patients tolerate the stress of cancer and its treatment? How are concomitant comorbid conditions managed?
At present, no established, valid way to assess comorbidity in older cancer patients exists. Such technology, with a solid conceptual and scientific base, promises a high positive clinical yield to assure quality cancer care for older patients if reliable and valid instruments can be integrated into oncology practice. Much preliminary scientific work must be performed. A synthesis of viewpoints on what to include in comorbidity assessment of older cancer patients and development approaches were expressed in a multidisciplinary working group convened by the National Institute on Aging and the National Cancer Institute. We share the key issues raised regarding complexities of comorbidity assessment and suggestions for scientific inquiry.
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INTRODUCTION
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ADVANCING AGE is associated not only with an increased vulnerability to cancer but also with other age-related chronic health problems (eg, heart disease, hypertension, diabetes, arthritis, and chronic obstructive pulmonary disease). Thus, a diagnosis of cancer in an older person is likely to be made in the context of that individual’s pre-existing health problems (ie, comorbidity), which introduces very important issues in clinical decision making and treatment for the oncologist. Evaluation of the comorbidity in an older person newly diagnosed with cancer and assessment of the severity of the various pre-existing conditions and their overall and individual impact on the cancer course are crucial to providing quality cancer care to older individuals. Appropriate and careful comorbidity assessment could improve the diagnostic acumen of clinicians in management of older patients and enhance patient outcomes such as cure, quality of survival, prevention of recurrence, limitation of deterioration and/or complications, and relief of current distress. More than likely, there would be some combination of these beneficial factors for older cancer patients.
Yet there is a major gap in the knowledge base required to ensure quality cancer care in older patients. What is the nature and severity of their comorbid health problems? How do the age-related conditions influence cancer treatment decisions, the clinical course of cancer, and patient recovery? How do already compromised older patients tolerate the stress of cancer and its treatment? How are the serious comorbid conditions managed in the presence of cancer? These are several fundamental questions. Further, how can the comorbidity of cancer patients be characterized and studied? How can reliable information on comorbidity be developed?
This paper presents a synthesis of various points of view on comorbidity assessment of older cancer patients. The information stems from discussions of a multidisciplinary working group convened by the National Institute on Aging (NIA) and the National Cancer Institute (NCI). The intention is to share these perspectives with clinicians to advance the groundwork for scientific inquiry on comorbidity assessment of older cancer patients. Studies are urgently needed not only to describe more accurately the concomitant comorbidity burden of older cancer patients encountered in patient care practice and clinical trials research settings but also to devise optimum therapy for older patients who have these age-associated health problems. The frame of reference and essential issues considered in the working group regarding comorbidity assessment and the pathways to advance research in this area are highlighted.
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CANCER BURDEN OF OLDER PATIENTS
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The 65+ age group truly bears a disproportionate burden of cancer in the United States population. Sixty percent of all incident tumors and 70% of all cancer mortality occur in 12.8% of the United States population age segment of 65 years and older.1,2 The unequal burden of cancer in older Americans is even more apparent when specific tumor sites are considered, for two thirds to three quarters of the major tumors common to men and women (cancers of the lung and bronchus, colon, rectum, stomach, urinary bladder, and pancreas) occur in this age group. Men 65 years and older bear the brunt of prostate cancer incidence (75%) and prostate cancer mortality (92%).1 Approximately one half of the incident breast cancer cases (47%) and breast cancer deaths (58%) affect women 65 years and older. The highest incidence and mortality rates occur with advancing age and peak in the 65+ age group.1
The demographic changes occurring in the United States and the national concern for the well being of the older segment of the population are gradually being reflected in clinical practice. By 2030, one in five persons will be 65 years and older.2 Cancer clinicians are seeing more and more older patients. There is increasing recognition of a need for integration of aging and cancer research in detection, diagnosis, treatment, and prognosis studies.
COMORBIDITY BURDEN
Newly-diagnosed older cancer patients who have lived into the later years of life are likely to have concurrent ailments, such as diabetes, chronic obstructive pulmonary disease, heart disease, arthritis, and/or hypertension. These are some of the more common health problems associated with advancing age that may affect treatment choice, patient prognosis, and survival.3-5 Four out of five older individuals 65 years and older have one or more chronic condition.6 In addition to the concurrent presence of chronic conditions, older individuals may have such geriatric syndromes as frailty, urinary incontinence, malnutrition, depression, and balance disorders. Although investigators have begun to address the coexistence of comorbidity and cancer in the elderly, research is in the preliminary phases of conceptual and measurement development.7-13 Limitations in functional status, such as self-reliance in eating, washing, toileting, dressing, mobility, and transportation, that are associated with the aging continuum in later years of the life span introduce an additional order of comorbidity assessment complexity as do other age-related declines in physical and physiologic functioning, cognitive impairment, and other incapacities. Levels of severity of comorbidity quite likely include additive and multiplicative relationships. Reexamination of comorbidity severity with this potential in mind may be the basis for generating indices that initiate measures of physical performance and disability.
Therapeutic risks are related to problems and conditions beyond the tumor site and disease stage. The impact of treatment (ie, surgery, radiation, and chemotherapy) versus probability of cure and survival must be ascertained. Tremendous variations exist in the clinical course of different tumors. These affect the choice of treatment modalities that, in turn, affect the interactions that occur among these factors and comorbidities in the aged host. The presence of multiple pathology in a cancer patient requires monitoring of the other health problems and attention to the various interactions that might occur with the cancer and its treatment. In addition, illness clustering and cumulative effects of the diseases, fluctuating health problems, and wavering nutritional status must be taken into account.
COMORBIDITY ASSESSMENT
Assessment of comorbidity in newly diagnosed older cancer patients is of concern to oncologists and other medical personnel. If an older person, already burdened with one or more age-related ailments, is diagnosed with cancer, the level of complexity for treatment of the malignancy and the management of the preexistent diseases may be substantially increased. Accurate assessment of an older patient’s comorbidity burden (ie, non-neoplastic diseases, and physical and physiologic problems), in addition to the customary classification of tumor characteristics (ie, tumor-node-metastasis staging and anatomic spread), provides valuable information that can be incorporated into cancer prognosis and treatment recommendations leading to improved individualized care.
Information on comorbidity in older cancer patients has been obtained in different ways. Approaches involve collecting data from personal interviews, first-hand review of cancer patients’ medical records, reviews of death certificates, use of administrative medical record databases (eg, discharge data), summary indices derived from the presence of selected conditions assigned severity scores, and, less frequently, the physical functioning of patients under surveillance. The indices approach the relationship between and among conditions in diverse ways. Conjoint effects of the comorbid conditions are usually not determined. The several comorbidity indices that exist offer varying assistance in comorbidity assessment. The measures are diverse in content, have different outcome goals, and limited prognostic perspectives.
With respect to candidate comorbidities, the explicit research question plays the principal role in the selection of the comorbid conditions for assessment. Severity of the disease or condition is also a primary determinant of the comorbidities included in research. Therefore, the concentration in comorbidity research is generally placed on the more prevalent comorbid diseases that are life threatening or difficult to control. Examples of these are certain types of heart disease (eg, arrhythmia and congestive heart failure), chronic obstructive pulmonary disease, insulin-dependent diabetes, liver disease, renal disease, and gastrointestinal problems. Other common problems, such as hypertension, arthritis, osteoporosis, lipid problems, thyroid/glandular deficiencies, and visual and hearing impairments, that could affect daily activity are also potential candidate comorbid conditions. Synergism of disease pairs and association of comorbidity and disability warrant explicit attention to special severity criteria. Health problems that arise because of the malignant tumor itself and/or its treatment (eg, anemia) are yet another category.
Gerontologists and geriatricians in the NIA/NCI working group introduced the set of conditions considered distinctly disabling and age relevant, such as balance, upper and lower body strength, gait limitations, cognition, sensory function, psychologic status, wavering decline, disease pairing, and nonrandom clusters of comorbidity. Oncologists and other cancer specialists posed varying conditions that could occur depending on the specific type of tumor diagnosed (eg, pathology caused by the tumor or its treatment such as renal failure, anemia, malnutrition, and adverse secondary effects of treatment such as cardiotoxicity, lymphedema, and peripheral neuropathy).
KEY POINTS
- No particular chronological age carries with it an a priori set of health problem conditions as an appropriate sorting variable. Older cancer patients may manifest multiple health problems that range in number from just a few to many and are present at different levels of severity in various domains. Thus, there is no one-size-fits-all instrument available for comorbidity assessment. No on-the-shelf assessment tool exists. There are coarse versus fine measurement approaches that might be used depending on the research questions. At times, even just three items (for memory registration and recall) could be useful. Also, there are pitfalls in too frequent measurement (eg, in analysis and utility) as one might obtain nonstable, transient behaviors.
- Various comorbid conditions overlap and contribute to patient-based complexity. Certain dimensions of illness-related conditions would be difficult to evaluate with comorbidity assessment tools (eg, deterioration over time). The minimal array of health and medical conditions (ie, diseases, age-related problems, and smoking behavior) that require evaluation before treatment need to be determined depending on the research questions.
- Physical disability in an older cancer patient has certain medical consequences not present in an older cancer patient with no disability. The physically impaired individual is likely to have greater health care needs that may include increased risk for falls and acute illnesses as well as the need for assistance with activities of daily living.
- Feasibility of collecting quality data on older cancer patients in an oncology setting could be problematic. Obtaining the relevant data, monitoring the information for consistency and quality, and organizing it for analyses in a nonresearch setting or in a research setting must be carefully thought through and demonstrated as workable. Data collection and study operations need to be adapted to the nonresearch and research settings using well-trained research associates.
- Specific tumors may require special comorbidity research questions because of their anatomic location, biologic behavior, disease stage, and impact on the patient and his/her pre-existing comorbid conditions.
- The question arises as to whether comorbidity indices should be developed to address specific outcomes (eg, mortality, quality of life, disability, and health care utilization). Comorbid conditions that influence physical functioning may differ from those that influence mortality. Another consideration is that comorbidity might have an impact on future physical functioning rather than that manifested at the current assessment (ie, preclinical disability).
- Clinicians caring for cancer patients must make their treatment decisions from among many possible therapeutic alternatives. Methods established by randomized clinical trials research that incorporate protocol guidelines and systematic reviews to understand the yield of assessment and treatment offer a special opportunity for the focus on comorbidity assessment of older cancer patients.
- Several NCI-sponsored cooperative study groups have established a focus on treatment of older cancer patients with special committees or ad hoc working groups. The challenge is to begin development of a knowledge base through the widely accepted mechanism of clinical trials research in the oncology community. A multidisciplinary study group such as that established by the European Organization for Research and Treatment of Cancer for quality-of-life assessment could be a model approach.
- NCI-sponsored cancer centers in geographic alignment with NIA-sponsored centers on aging should be encouraged to apply their combined resident clinical, epidemiologic, and social science expertise on behalf of older cancer patients with respect to comorbidity assessment. This partnership could be expanded to involve the Veterans Administration Medical Centers.
- Development of closer ties between oncologists and geriatricians will contribute to progress and collaborative success on comorbidity assessment in older patients with cancer. Fundamental knowledge about the processes of aging and the diseases of the elderly need to be brought into the mainstream practice of oncology.
- The NIA and NCI should consider convening a working conference with invited speakers. One of the products could be a monograph that includes the papers presented with reports on current work underway on comorbidity assessment in older cancer patients.
- A task force approach of seven to 10 persons to make headway in developing collaborative alliances and intergroup studies should be considered.
SUGGESTIONS FOR SCIENTIFIC INQUIRY
Pilot studies to initiate comorbidity assessment of older cancer patients.
Establish communication among clinicians, social scientists, and epidemiologists regarding approaches to assess comorbid conditions and their impact on older persons afflicted with cancer. Pilot data are needed.
Prospective studies documenting prevalence of comorbidity and impact on cancer diagnosis, prognosis, and the efficacy and safety of therapy.
Such studies can be organized as companion studies to treatment trials within the NCI Clinical Trials Cooperative Groups designed as targeted comorbidity studies associated with specific malignancies and treatment protocols or as stand-alone investigations (eg, patient roster approach).
Prospective studies within the NCI-designated cancer centers.
These investigations would take advantage of the established cancer center catchment areas, the strength of consortia, and resident expertise within the various centers with adequate patient activity.
Population-based studies.
Such investigations could be organized as NCI Surveillance, Epidemiology, and End-Results special studies, as ancillary studies to the NCI research networks established for other purposes (eg, family genetics studies), or designed for selected population catchment areas.
Extant data can be used with a minimally extended effort.
Patient evaluation data collected for treatment purposes (eg, the patient work-up) with a minimally extended effort can be used. Longitudinal studies established by the NIA, NCI, and other federal agencies may be explored (eg, the Health Care Financing Administration data and the NIA Baltimore Longitudinal Study).
Comparative methodology studies and demonstration of feasibility of data collection demonstration projects.
Some of this work is already underway. Developments of instrumentation and study logistics are fundamental to comorbidity assessment of older persons with cancer. With the many methodologic challenges inherent in comorbidity assessment indicated in working group discussions by researchers in oncology and geriatric medicine, careful observational studies preliminary to launching large-scale efficacy studies need to be performed.
Efforts to augment conventional data collection activities in cancer care.
Comorbidity assessment should be attached to established data collection efforts, such as performance evaluation with Eastern Cooperative Oncology Group and Karnofsky measures and the tumor-node-metastasis staging system.
Studies focused on varying patient outcome (eg, cure, survival, quality of life, patient and family preferences, and pain relief).
Comorbidity and its overall assessment influences clinical decision making to benefit older patients, depending on patient, family, and physician outcome goals.
Patterns of care studies conducted in the community setting.
Systematic inquiry of physician course of action (ie, treatment and decisions) at the community level.
Methods development.
Brief, concise, nonthreatening (to the physician as well as the patient) assessment tools/inventories that document the prevalence of chronic conditions, ascertain their severity, and obtain basic data on physical and cognitive functioning in older cancer patients need to be designed and implemented.
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DISCUSSION
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The presence of age-related problems in newly diagnosed older cancer patients is bound to have an impact on the course of their cancer treatment. Studies aimed at coordinating the multiple problems in cancer treatment of the elderly and those varied problems intrinsic to old age are urgently needed. Comorbidity assessment is one of many issues that need to be addressed. Such technology, with a solid conceptual and clinical base, promises a high positive clinical yield if reliable and valid instruments can be integrated into oncology practice. However, there is much preliminary work to be done. The strategy should be incremental and systematic with the goal of incorporating the process of comorbidity assessment eventually into the initial history and physical review of the older patient diagnosed with cancer (ie, the patient work-up).
There are several pervasive issues. Comorbidity assessment should involve determination of severity of other diseases and functional impairment of the cancer patient in addition to that of the tumor. Appraisal should be made of both physical and cognitive functioning and limitations of the person afflicted with cancer. The selection of relevant outcomes for prognostic implications may vary as appropriate to the study objectives. One must be mindful that physical changes are not disconnected from the social and psychologic events and changes going on in the older patient’s life. Underscoring these, it is evident that the comorbidity assessment research agenda directed at older patients diagnosed with cancer requires an interdisciplinary team approach.
APPENDIX
Working Group participants included: Kathy S. Albain, MD, Loyola University Medical Center, Maywood, IL; Lodovico Balducci, MD, and Martine Extermann, MD, H. Lee Moffitt Cancer Center, Tampa, FL; Harvey Jay Cohen, MD, Duke University Medical Center, Durham, NC; Barbara Conley, MD, Working Group Co-organizer, Lynn A.G. Ries, MS, and Claudette G. Varricchio, DSN, RN, FAAN, Working Group Co-organizer, National Cancer Institute; Evan Hadley, MD, Stanley Slater, MD, and Rosemary Yancik, PhD, Working Group Co-organizer, National Institute on Aging, Bethesda; Linda P. Fried, MD, MPH, Johns Hopkins Medical Institutions, Baltimore; Margaret N. Wesley, PhD, Information Management Services, Silver Spring, MD; Patricia A. Ganz, MD, Working Group Chairperson, University of California, American Cancer Society Professor, Los Angeles; William Satariano, PhD, University of California, Berkeley, CA; Margaret Kemeny, MD, Stonybrook University Hospital, Stonybrook; Alice B. Kornblith, PhD, Beth Israel Medical Center, New York City; Jerome W. Yates, MD, Roswell Park Cancer Center, Buffalo, NY; Hyman B. Muss, MD, Fletcher Allen Health Care, (Medical Center Hospital of Vermont Campus), Burlington, VT; Jay Piccirillo, MD, Washington University, St Louis, MO; Judith Salerno, MD, Department of Veterans Affairs, Washington, DC; Rebecca Silliman, MD, Boston Medical Center, Boston, MA; Stephanie Studenski, MD, University of Kansas Medical Center, Kansas City, KS; Jan Willem Coebergh, MD, PhD, Integraal Kancercentrum Zuid, Eindhoven, the Netherlands; and Lazzaro Repetto, MD, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
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NOTES
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The multidisciplinary working group, which convened on July 29-30, 1999, was comprised of individuals with expertise in oncology, geriatric medicine, other specialties and health professions, epidemiology, and social science. A list of participants is provided in the Appendix.
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Submitted July 7, 2000;
accepted October 3, 2000.
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Corticosteroids Underemployment in Delayed Chemotherapy-Induced Nausea and Emesis With Poor Adherence to American Society of Clinical Oncology Guidelines: Is This a Reasonable Clinical Choice for the Elderly?
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K. Monson, D. A. Litvak, and R. J. Bold
Surgery in the Aged Population: Surgical Oncology
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K. W.L. Yee, J. L. Pater, L. Pho, B. Zee, and L. L. Siu
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Y.-L. Zheng, C. A. Loffredo, Z. Yu, R. T. Jones, M. J. Krasna, A. J. Alberg, R. Yung, D. Perlmutter, L. Enewold, C. C. Harris, et al.
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Carcinogenesis,
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T. L. Lash, S. S. Thwin, N. J. Horton, E. Guadagnoli, and R. A. Silliman
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M. Hewitt, J. H. Rowland, and R. Yancik
Cancer Survivors in the United States: Age, Health, and Disability
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N. M. Aziz
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L. Sarna, G. Padilla, C. Holmes, D. Tashkin, M. L. Brecht, and L. Evangelista
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R. T. Chlebowski, E. Aiello, and A. McTiernan
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TOP
ABSTRACT
INTRODUCTION
