Inclusion of Comorbidity in a Staging System for Head and Neck Cancer

Inclusion of Comorbidity in a Staging System for Head and Neck Cancer

ABSTRACT: The widespread use of the TNM staging system has helped standardize the classification of cancers. Despite its excellence in describing a tumor's size and extent of anatomic spread, the TNM system does not account for the clinical biology of the cancer. Clinical factors, such as symptom severity, performance status, and comorbidity, which are important for classification, prognostication, and evaluation of treatment effectiveness, remain excluded from this system. In several studies of cancer prognosis, the presence of severe comorbidity was found to dramatically influence survival statistics and the evaluation of treatment effectiveness. A statistical technique known as conjunctive consolidation was used to incorporate comorbidity into the TNM staging system and maintain the four category system. Utilizing this technique, comorbidity was added to the TNM system for laryngeal cancer to create a composite staging system. Quantitative evaluation of the new system showed that the addition of comorbidity provides improved prognostic precision over TNM stage alone. [ONCOLOGY 9(9):831-848, 1995]


The tumor, node, metastasis (TNM) system of cancer classification
was originally described by Denoix and Schwartz [1] in 1948 and,
in 1953, was incorporated by the International Union Against Cancer
(Union International Contre le Cancer, UICC) and the International
Congress of Radiology into a formal classification system for
cancer [2]. The TNM system was adopted in the US in 1959, when
the American College of Surgeons, American College of Radiology,
College of American Pathologists, American College of Physicians,
American Cancer Society, and National Cancer Institute cosponsored
the formation of the American Joint Committee for Cancer Staging
and End Results Reporting [3]. Its stated purpose was "to
develop systems for the clinical classification of cancer which
would be of value to practicing American physicians" [4].

During the past 30 years, the AJCC has worked to develop TNM definitions
and stage classifications for all disease sites and subsites,
revise definitions and classifications based on the results of
clinical studies, and educate physicians and other health-care
professionals about the TNM classification system. In 1988, the
AJCC reached agreement with the UICC for a common TNM and stage
classification system, thereby resolving many minor differences
that had previously prevented the creation of a single tumor classification

TNM-A Morphologic Staging System

The TNM system classifies a cancer's spread from primary to distant
sites. In the general TNM approach, the six T categories-T0, Tis,
T1, T2, T3, and T4-refer to the extent of the primary tumor; the
four N categories-N0, N1, N2, and N3-denote the degree of involvement
of regional nodes; and the two M categories-M0 and M1-designate
the absence or presence of distant metastasis.

For each patient, the individual T, N, and M category ratings
are combined in tandem to form expressions such as T2, N1, M0
or T3, N2, M1. Because six categories of T, four categories of
N, and two categories of M create 48 possible ratings for the
TNM expressions, stage groupings (I, II, III, and IV) were created
by combining categories to ease statistical analyses. The TNM
system is thus an exclusively morphologic classification, offering
a reasonably precise description of the anatomic extent
of tumor at a specific time.

Clinical Biology of Cancer

The form of the tumor can be expressed in gross anatomic terms
(TNM index), microscopic terms (eg, cell type, degree of differentiation),
and biomolecular terms (eg, tumor markers, ploidy). The function
of the tumor can be described by clinical effects that create
severity of illness within the patient. The tumor's functional
effects are manifested by the type, duration, and severity of
cancer symptoms (eg, weight loss, fatigue) [5-10] and by the performance
or functional status of the host [11,12].

Another important aspect of clinical biology is the comorbidity,
or the "setting" in which the cancer occurs. Although
unrelated to the cancer itself, the patient's concomitant disease(s)
can affect the clinical course of cancer, choice of treatment,
and prognosis [13-17].

Shortcomings of TNM System

Despite its excellence in describing a tumor's size and extent
of anatomic spread, the TNM system does not account for the clinical
biology of the cancer [18-20]. A substantial amount of clinical
research has demonstrated the prognostic shortcomings of the TNM
system (unpublished data, JF Piccirillo, MD, and AR Feinstein,
MD; and references 5, 12, and 21-24), while several editorials
have requested improvements in it (unpublished data, JF Piccirillo,
MD, and AR Feinstein, MD; and references 20, 25, and 26). Nevertheless,
no significant modifications have been made in the TNM
system since its creation. In particular, important patient-based
prognostic factors, such as symptom type and severity, severity
of comorbidity, and functional capacity, are excluded. Despite
unequivocal evidence of the prognostic importance of symptoms,
performance status, and comorbidity, the AJCC system remains relentlessly
confined to morphologic data.

Prognostic Importance of Comorbidity

Many people with cancer also have other nonneoplastic diseases.
These comorbidities may be so severe as to prohibit the use of
preferred antineoplastic therapie and impact on 3- and 5-year
survival statistics. In several studies of cancer prognosis, the
presence of comorbidity was found to dramatically affect survival
and the evaluation of treatment effectiveness [7,16,21,27-30].

Prognostic Comorbidity

Prognostic comorbidity [31] refers to comorbidity severe enough
to impact on survival rates. Examples of prognostic comorbidity
are significant cardiac disease, severe hypertension, far-advanced
tuberculosis, severe liver disease, and recent severe stroke.
Examples of nonprognostic comorbidity include a history of "mild"
hypertension that is well controlled with medication, congestive
heart failure or myocardial infarction of more than 6 months duration,
recurrent asthma attacks without underlying lung disease, and
slight gastrointestinal bleeding not requiring transfusion. As
shown in Table 1, 5-year survival rates in a variety of cancers
are dramatically worse in patients with prognostic comorbidity
than in those without prognostic comorbidity.

Comorbidity vs Tumor Size and Stage

In many cancers, comorbidity is prognostically more important
than tumor size or stage. The cancers for which comorbidity is
particularly important are those which are not rapidly fatal and
which affect people who are middle-aged or older (ie, over age
50 years). These include cancers of the breast, prostate,7 oral
cavity, pharynx and larynx [16,29], bladder, ovary, and uterus
[17], as well as non-Hodgkin's lymphoma. Based on recent incidence
rates, these cancers represent approximately 61% of all cancers
for men and 65% for women.

The importance of comorbidity is clear from these statistics,
and yet the present cancer staging system does not contain this
important information. As several valid comorbidity instruments
now exist, the continued exclusion of standardized comorbidity
information from cancer statistics appears to be a major omission.

Specific Comorbidity Instruments

Comorbidity instruments can be classified into two groups, depending
on the origin of the data: (1) instruments that rely on primary
data and (2) instruments that are based on secondary data.
Primary data are collected from physicians or nurses or through
chart reviews. Secondary data are derived from administrative
and financial databases main- tained by hospitals, insurance companies,
and state and federal governments.

Instruments Derived from Primary Data

Comorbidity measures that rely on primary data include the Kaplan-Feinstein
Index [31], the Charlson Co-Morbidity Index [15], and the Index
of Co-Existent Disease [32].

The Kaplan-Feinstein Comorbidity Index was developed from
a study of the impact of comorbidity on 5-year survival outcomes
for patients with diabetes mellitus. In this index, specific diseases
and conditions are classified as mild, moderate, or severe based
on the severity of organ decompensation. An overall comorbidity
score is assigned according to the highest level of decompensation.

The Charlson Comorbidity Index was created from studies
of 1-year mortality among patients admitted to a medical unit
of a teaching hospital. It is a weighted index that takes into
account the number and seriousness of comorbid diseases. The scoring
system for this instrument assigns weights of 1, 2, 3, and 6 for
each of the comorbid diseases present at initial assessment, and
derives from these a total score that determines the patient's
overall prognostic status.

The Index of Co-Existent Disease (ICED) predicts length
of stay and resource utilization after hospitalization for surgical
procedures. To calculate the overall burden of comorbidity, ICED
assesses the patient's status in two separate components: physiologic
and functional burden.


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