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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: [email protected].
2001 by American Society of Clinical Oncology.
0732-183X/01/1904-1147
1147Journal of Clinical Oncology,Vol 19, No 4 (February 15), 2001: pp 1147-1151Downloaded from jco.ascopubs.org on September 27, 2014. For personal use only. No other uses without permission.
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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-
1148 YANCIK ET AL
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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.
1149COMORBIDITY ASSESSMENT OF OLDER CANCER PATIENTS
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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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