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P e r s p e c t i v e s o n C o m o r b i d i t y a n d C a n c e r i n O l d e r P a t i e n t s :A p p r o a c h e s t o E x p a n d t h e K n o w l e d g e B a s e

By Rosemary Yancik, Patricia A. Ganz, Claudette G. Varricchio, and Barbara Conley

Abstract: Not only do persons 65 years and olderbear a disproportionate burden of cancer, advancingage is associated with increased vulnerability to otherage-related health problems. Newly diagnosed oldercancer patients who have lived into later years of lifemay have concurrent ailments (eg, diabetes, chronicobstructive pulmonary disease, heart disease, arthritis,and/or hypertension) that could affect treatmentchoice, prognosis, and survival. The clinician must oftenmake cancer treatment decisions in the context of anolder individuals pre-existing health problems (ie, co-morbidity). Ways to produce reliable information oncomorbidity that can be effectively used in evaluationof older cancer patients are urgently needed. What is

the nature and severity of the older patients comorbidhealth problems? How do other age-related conditionsinfluence treatment decisions and the cancer course?How do already compromised older patients tolerate

the stress of cancer and its treatment? How are concom-itant comorbid conditions managed?

At present, no established, valid way to assess co-morbidity in older cancer patients exists. Such technol-ogy, with a solid conceptual and scientific base, prom-ises a high positive clinical yield to assure quality cancercare for older patients if reliable and valid instrumentscan be integrated into oncology practice. Much prelim-inary scientific work must be performed. A synthesis of

viewpoints on what to include in comorbidity assess-ment of older cancer patients and development ap-proaches were expressed in a multidisciplinary work-ing group convened by the National Institute on Agingand the National Cancer Institute. We share the key

issues raised regarding complexities of comorbidityassessment and suggestions for scientific inquiry.J Clin Oncol 19:1147-1151. 2001 by American

Society of Clinical Oncology.

A DVANCING AGE is associated not only with anincreased vulnerability to cancer but also with otherage-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 individuals

pre-existing health problems (ie, comorbidity), which intro-

duces very important issues in clinical decision making andtreatment 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 as-

sessment could improve the diagnostic acumen of clinicians

in management of older patients and enhance patient out-

comes 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 oldercancer 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 recov-

ery? 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 inten-

tion is to share these perspectives with clinicians to advance

the groundwork for scientific inquiry on comorbidity assess-

ment of older cancer patients. Studies are urgently needed

not only to describe more accurately the concomitant

comorbidity burden of older cancer patients encountered in

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, Uni-versity of California, Los Angeles, CA.

Submitted July 7, 2000; accepted October 3, 2000.

The multidisciplinary working group, which convened on July 29-30,

1999, was comprised of individuals with expertise in oncology, geri-

atric medicine, other specialties and health professions, epidemiology,

and social science. A list of participants is provided in the Appendix.

Address reprint requests to Rosemary Yancik, PhD, National Insti-

tute on Aging, Geriatrics Program, Suite 3E327, 7201 Wisconsin Ave,

Bethesda, MD 20892-9205; email: yancikr@exmur.nia.nih.gov.

2001 by American Society of Clinical Oncology.

0732-183X/01/1904-1147

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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 refer-

ence and essential issues considered in the working group

regarding comorbidity assessment and the pathways to

advance research in this area are highlighted.

CANCER BURDEN OF OLDER PATIENTS

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 aneed for integration of aging and cancer research in detec-

tion, 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

Inaddition 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 func-

tional 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 assess-

ment 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. Tre-

mendous 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 interac-

tions that might occur with the cancer and its treatment. In

addition, illness clustering and cumulative effects of the

diseases, fluctuating health problems, and wavering nutri-

tional 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 malig-nancy and the management of the preexistent diseases may

be substantially increased. Accurate assessment of an older

patients 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 im-

proved individualized care.

Information on comorbidity in older cancer patients has

been obtained in different ways. Approaches involve col-

lecting data from personal interviews, first-hand review ofcancer patients medical records, reviews of death certifi-

cates, 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 sur-

veillance. 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 assis-

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tance in comorbidity assessment. The measures are diverse

in content, have different outcome goals, and limited prog-

nostic 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 concen-

tration 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 de-

ficiencies, 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 pe-

ripheral 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 andare 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 ap-

proaches 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 co-

morbidity 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 col-

lection and study operations need to be adapted to the

nonresearch and research settings using well-trained re-

search associates.

Specific tumors may require special comorbidity research

questions because of their anatomic location, biologic be-

havior, 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 utiliza-tion). Comorbid conditions that influence physical function-

ing 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.

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There are several pervasive issues. Comorbidity assess-

ment 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 appro-

priate 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

patients 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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1151COMORBIDITY ASSESSMENT OF OLDER CANCER PATIENTS

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