Abstract

BACKGROUND
The National Cancer Data Base (NCDB) represents a national electronic registry system
now capturing nearly 60% of incident cancers in the U. S. In combination with other
Commission on Cancer programs, the NCDB offers a working example of voluntary,
accurate, cost-effective "outcomes management" on a both a local and national scale. In
addition, it is of particular value in capturing clinical information concerning rare
cancers, such as those of the thyroid.
METHODS
For the accession years 1985-1995, NCDB captured demographic, patterns-of-care,
stage, treatment, and outcome information for a convenience sample of 53,856 thyroid
carcinoma cases (1% of total NCDB cases). This article focuses on overall 10-year
relative survival and American Joint Committee on Cancer (AJCC) (3rd/4th edition)
stage-stratified 5-year relative survival for each histologic type of thyroid carcinoma.
Care patterns also are discussed.
RESULTS
The 10-year overall relative survival rates for U. S. patients with papillary, follicular,
Hrthle cell, medullary, and undifferentiated/anaplastic carcinoma was 93%, 85%, 76%,
75%, and 14%, respectively. For papillary and follicular neoplasms, current AJCC
staging failed to discriminate between patients with Stage I and II disease at 5 years.
Total thyroidectomy lymph node sampling/dissection represented the dominant
method of surgical treatment rendered to patients with papillary and follicular
neoplasms. Approximately 38% of such patients receive adjuvant iodine-131
ablation/therapy. At 5 years, variation in surgical treatment (i.e., lobectomy vs. more
extensive surgery) failed to translate into compelling differences in survival for any
subgroup with papillary or follicular carcinoma, but longer follow-up is required to
evaluate this. NCDB data appeared to validate the AMES prognostic system, as applied
to papillary cases. Younger age appeared to influence prognosis favorably for all
thyroid neoplasms, including medullary and undifferentiated/anaplastic carcinoma.
NCDB data also revealed that unusual patients diagnosed with
undifferentiated/anaplastic carcinoma before age of 45 years have better survival.
CONCLUSIONS
The NCDB system permits analysis of care patterns and survival for large numbers of
contemporaneous U. S. patients with relatively rare neoplasms, such as thyroid
carcinoma. In this context, it represents an unsurpassed clinical tool for analyzing care,
evaluating prognostic models, generating new hypotheses, and overcoming the volume-
related drawbacks inherent in the study of such neoplasms. [See editorial on pages
2434-6, this issue.] Cancer 1998;83:2638-2648. 1998 American Cancer Society.
The National Cancer Data Base (NCDB), a joint
project of the Commission On Cancer (COC) of the
American College of Surgeons (ACoS) and the
American Cancer Society (ACS), assesses both patient
care and treatment outcomes at an institutional,
regional, and national level.
Annually, each institution voluntarily submitting data
receives a detailed report comparing institutional and
national results. Institutions use this information to
benchmark and evaluate trends in both cancer care and
outcomes. The NCDB, when viewed in combination
with other COC programs operating at both the local
and national level, represents a working example of a
national "outcomes management system." It offers a
fine example of how voluntary, collaborative,
professional efforts can reduce the morbidity and
mortality of cancer through application of an
"outcomes management" approach.1
The NCDB began operations in 1989. Through
multiple calls for data, cases from 1985 through 1995
have been accessioned and are available for analysis.
For the 1995 accession year, the NCDB captured 60%
of cancer cases treated in the U.S. By current estimates,
a new linkage between the NCDB and the COC's
Cancer Program Approval System will increase
accessions to nearly 80% of 1998 cancer cases in the U.
S. Benefiting from the high degree of professional
volunteerism that has typified COC-ACoS-ACS
collaborations, the national NCDB office runs on an
annual direct-cost budget of only $800,000. The
popularity, utility, and cost-effectiveness of this system
offers an unsurpassed example of how professional
volunteerism, standardization, computing technology,
and careful planning can combine to create a valuable
tool for benchmarking and improving health care.
With increasing case accrual, the NCDB also has
emerged as a superb tool for obtaining
contemporaneous data concerning patterns of care and
outcomes for rare neoplasms such as thyroid
carcinoma. In the U.S. in 1994, newly diagnosed
thyroid carcinoma was reported in approximately
13,000 people. The same year, approximately 1000
people died of this disease.2Although its incidence
appears to be increasing, thyroid carcinoma, accounting
for only 1% of all reportable malignancies, remains
rare both in the U.S. and worldwide.3, 4 This fact,
combined with the indolence of this disease and its
generally favorable prognosis, serves to undermine the
comparative study of different treatments by
prospective randomized clinical trials. Current
treatment recommendations generally are based on
retrospective studies derived from analyses of patients
treated in the distant past and collected over several
decades.5-12 Recognizing that risk models derived
from retrospective analysis of one population,
particularly if relatively homogeneous (e.g., all treated
at one institution, from one geographic region, from
one organization, treated in distant past, etc.), may not
predict outcomes for a different population, the value
of data derived from a relatively contemporaneous
national source such as the NCDB13cannot be
underestimated.
This report summarizes NCDB findings concerning
thyroid carcinoma in the U.S., focusing on the period
between 1985-1995.
METHODS
This article on thyroid carcinoma continues the
tradition of analyzing data voluntarily submitted to the
NCDB to determine national patterns of patient care
and to assess outcomes. Using standardized definitions
and uniform data formats, the NCDB annually collects
data for all forms of cancer from hospitals throughout
the U.S., the majority of which have COC-approved
cancer programs. The methods of the NCDB have been
described previously.14
This analysis, based on seven annual calls for data
issued since 1989, draws on experience with patients
diagnosed between 1985-1995. The NCDB's "calls for
data" routinely were transmitted to approximately 2100
hospitals (1340 participating in COC Approval
Programs and 760 others), as well as to all known
central and state registries and all known software
vendors and suppliers.
The NCDB cohort represents data from U.S.
institutions located in all 50 states, Puerto Rico, and the
District of Columbia. Each hospital receives an annual
report comparing its own data with that of the entire
NCDB cohort to facilitate assessment of its own care
patterns and outcomes.
NCDB cancer registry data are coded according to the
schema published in the Data Acquisition Manual,15 the 3rd and
4th editions of the American Joint Committee for
Cancer (AJCC) Manual for Staging of Cancer,16, 17 and the
second edition of the International Classification of Disease for
Oncology (ICD-O-2).18 Formats for data reporting and
electronic transmission to the NCDB are uniform. Data
is transmitted to the NCDB by diskette or data tapes.
To preserve confidentiality, individual patient
identifiers such as social security numbers, names, etc.
are collected by individual participating registries, but
are neither transmitted to nor collected by the NCDB.
Hospital cancer committees or their equivalent
supervise the quality of institutional case finding,
abstracting, internal reviews of abstracts by registry
staff, and hospital-based computer data edits. On
submission to the NCDB, all data were checked
electronically for valid codes and for logic between
data items. Record linkage to detect duplicates was
performed using gender, three-digit site code, birth
date, and zip code. Cases judged to be duplicates were
removed from the analytic file.
To minimize the number of patients with unknown
stage in this study, a combination AJCC stage was
used. Each patient was assigned the AJCC pathologic
stage, if available. If a particular T, N, or M
classification was not confirmed pathologically, then
the patient was assigned the appropriate AJCC clinical
stage, and the "combined stage" was reported. Of the
53,856 patients in this study, 17,299 did not have an
assigned pathologic stage. Of these, 5418 did have an
assigned clinical stage, leaving 11,881 patients (22.1%)
without a known stage. The majority of AJCC unstaged
patients were submitted by central registries, which, in
the U. S., often do not explicitly collect AJCC stage
information.
This analysis covers primary tumors of the thyroid
gland (ICD-O-2 site C73.9) coded as one of the five
major histologies: papillary (8050/3, 8340/3, and
8260/3), follicular (8330/3, 8332/3, and 8331/3),
medullary (8510/3 and 8511/3), Hrthle cell (8290/3),
and undifferentiated/anaplastic (8020/3 and 8021/3,
respectively).
Relative survival analyses were conducted in the usual
fashion, and adjusted using expected survival rates for
the U.S. population in 1980. 16 Both descriptive and
survival analyses for this article were performed using
SPSS software.19
Due to the methodology of the data collection, this
article is comprised of descriptive statistics to identify
current patterns of care and outcomes. Inferential
statistics regarding the multiple comparisons contained
herein are not warranted due to the lack of a priori
hypotheses and the very large sample size, representing
a substantial proportion of the population under study.
These facts contravene the assumptions of inferential
statistics and could confound results. We advocate a
straightforward interpretation of these data and do not
offer statistical comparisons. We do consider these data
suitable for benchmarking, for describing care patterns,
for assessing national community-based outcomes, and
for generating new hypotheses.
RESULTS
Table 1 summarizes accrual and histology by era
(1985-1990 and 1991-1995). Over the 10-year period
between 1985-1995, the NCDB captured data on a total
of 53,856 cases: 42,686 papillary carcinomas, 6764
follicular carcinomas, 1585 Hrthle cell carcinomas,
1928 medullary carcinomas, and 893
undifferentiated/anaplastic carcinomas. Over the 10-
year period, submissions to the NCDB increased
considerably, but proportional representation of each
histology varied only slightly.
Table 1. Percentage of Thyroid Carcinoma Cases by Diagnosis Year and Histologic Subgroup

1985-1990 1991-1995 Total

Histologic subgroup

Papillary 17,397 77.9 25,289 80.2 42,686

Follicular 3169 14.2 3595 11.4 6764

Hrthle cell 594 2.7 991 3.1 1585

Medullary 829 3.7 1099 3.5 1928

Undifferentiated/anaplastic 354 1.6 539 1.7 893

Total 22,343 100.0 31,513 100.0 53,856

Figure 1 (9K) depicts age distribution for the 53,856

patients by histology.
 Figure 1.
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Age distribution (in percent) of thyroid carcinoma by
histology.
In 1988, with publication of the 3rd edition of the
AJCC Manual for Staging of Cancer, both stage definitions and
stage groupings for this site changed. Definitions and
groupings remained the same through subsequent
changes (i.e., same for 3rd, 4th, and 5th editions).
Table 2 reveals stage distribution for patients staged
according to the 3rd or 4th editions of the AJCC
manual.
Table 2. Percentage of 1990-1994 Thyroid Carcinoma Cases by Combined Stagea and Histologic
Subgroup

Combined Stage Group

III Unknown
I (%) II (%) IV (%) Total (%) No.
(%) (%)
 Combined Stage Group

III Unknown
I (%) II (%) IV (%) Total (%) No.
(%) (%)

a
This table only includes cases that were staged according to the 3rd or 4th editions of the American Joint Committee on Cancer staging manua

Histologic subgroup

Papillary 56.9 14.4 10.3 2.1 16.4 100.0 34,79

Follicular 41.2 26.7 6.9 7.2 17.9 100.0 5271

Hrthle cell 20.8 35.1 9.3 5.7 29.0 100.0 1310

Medullary 16.5 29.6 26.8 11.0 16.0 100.0 1550

Undifferentiated/anaplastic 0.0 0.0 0.0 100.0 0.0 100.0 741

Total 51.5 16.8 10.3 4.8 16.6 100.0

Cases 22,486 7335 4491 2091 7263 43,66

As seen in Table 3, over the 10-year period, surgical

treatment for the majority of patients with thyroid
carcinoma was comprised of near-total or total
thyroidectomy. For papillary, follicular, and Hrthle
cell carcinoma, ipsilateral lobectomy with isthmectomy
was performed in 18.1%, 25.2%, and 24.7% of cases,
 respectively. Lymph node sampling appeared more
popular than formal, comprehensive lymph node
dissection; however, lymph node-directed treatment
was not practiced routinely for any histology.
Table 3. Percentage of Thyroid Carcinoma Cases by Type of Surgery and Histologic Subgroup

Near- Totalbwithout Totalcwith T

None/unknown Lobectomy
totala LND LND L

LND: lymph node dissection; rad: radical; mod: modified.

a
Near-total thyroidectomy.
b
Total thyroidectomy without lymph node dissection.
c
Total thyroidectomy with limited lymph node dissection.
d
Total thyroidectomy with radical or modified lymph node dissection.

Papillary 5.4 18.1 16.9 26.1 14.6 7.

Follicular 7.8 25.2 15.2 30.5 6.8 2.

Hrthle cell 5.9 24.7 16.1 32.7 7.8 2.

Medullary 11.4 8.9 6.8 24.2 17.6 19

Undifferentiated/anaplastic 47.8 13.4 9.0 8.2 5.7 4.

Total 6.6 18.8 16.2 26.5 13.4 6.

Cases 3562 10,103 8705 14,276 7191 36

Table 4 confirms that, for this site, treatment during the

10-year period was comprised overwhelmingly of
surgery or surgery plus radiotherapy (usually iodine-
131 [I-131] rather than external beam). Many patients
received postoperative hormonal replacement or
hormonal suppression therapy with thyroid hormone or
analogue, but the NCDB data set fails to capture this
information specifically. Systemic chemotherapy plays
little role in the current treatment of thyroid carcinoma,
and the percentage of patients receiving "other
treatment" (surgery or radiation plus chemotherapy,
etc.) was low.
Table 4. Percentage of Thyroid Carcinoma Cases by Treatment Combination and Histologic
Subgroup

Surgery +
Surgery Radiation Other None Tota
radiation

Histologic subgroup

Papillary 56.3 38.3 1.6 0.0 3.7 100.0

Follicular 53.6 38.6 3.3 0.1 4.4 100.0

Hrthle cell 61.6 32.5 2.1 0.0 3.8 100.0

Medullary 71.8 16.8 4.1 1.4 5.9 100.0

Undifferentiated/anaplastic 17.4 34.8 33.1 2.5 12.2 100.0

Total 56.0 37.3 2.5 0.1 4.0 100.0

 Surgery +
Surgery Radiation Other None Tota
radiation

Cases 30,186 20,108 1327 74 2161 53,85

Figure 2 (8K) depicts 10-year relative survival rates by

histology. Patients with undifferentiated/anaplastic
carcinoma (only 1.7% of the 53,856 cases) had a
dismal prognosis, with only 14% surviving 10 years.
However, for the vast majority of patients with thyroid
carcinoma, 10-year survival rates appear excellent.

Figure 2.
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Relative survival by histology of thyroid carcinomas
diagnosed between 1985-1990.
Table 5 emphasizes the influence of age on the
prognosis of patients with thyroid carcinoma, with both
5-year and 10-year survival rates for all histologies
(i.e., not just papillary and follicular carcinomas)
influenced by this factor.
 Table 5. Thyroid Carcinoma 5-Year/10-Year Relative Survival (%) by Histologic Subgroup and
Age

< 45 45-59 60-69 70-79 80+

Histologic subgroup % % % % %

a
Insufficient numbers for reliable 10-year relative survival calculation.

Papillary 98/97 96/85 92/65 86/47 82/a

Follicular 98/98 92/66 85/57 83/a 62/a

Hrthle cell 97/a 91/90 92/0 92/70 53/a

Medullary 86/84 81/80 72/63 70/a 68/a

Undifferentiated/anaplastic 55/a 13/a 13/a 13/a 14/a

To simplify presentation of histology specific data

pertaining to 5-year stage-stratified survival, prognostic
models, and other factors, we have subdivided the
remainder of this section.
Papillary and Follicular Carcinoma
("Differentiated Thyroid Carcinoma")
Many pathologists fail to include an assessment of
grade for papillary and follicular carcinoma. However,
Table 6 confirms the contention by some that tumor
grade strongly influences prognosis.
Table 6. Thyroid Carcinoma 5-Year/10-Year Relative Survival (%) by Histologic Subgroup and
Histologic Grade

Histologic Grade

1 2 3

Histologic subgroup % (n) % (n) % (n)

Papillary 98/86 (2365) 93/73 (760) 70/68 (254)

Follicular 97/47 (878) 85/65 (200) 59/52 (167)

Figures 3 (5K) and 4 (5K) depict 5-year stage-stratified

survival according to AJCC 3rd and 4th edition staging.
Only slight differences in prognosis between the two
histologies were noted, but the prognosis for Stage III
and Stage IV patients with follicular thyroid carcinoma
appeared marginally worse.
 Figure 3.
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Relative survival of papillary thyroid carcinomas diagnosed
between 1985-1990 and staged according to definitions from
the 3rd/4th editions of the American Joint Committee on
Cancer (AJCC) staging system.

Figure 4.
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Relative survival of follicular thyroid carcinomas diagnosed
between 1985-1990 by American Joint Committee on Cancer
(AJCC) stage.
Tables 7 and 8 illustrate treatment-related 5-year
survival comparisons for each of the following
categories of papillary thyroid carcinoma and for each
of the following categories of follicular carcinoma: T-
1, N-0, M-0; T-4, N-0, M-0; any T, N-0, M-0; any T,
N-1, M-0; any T, any N, M-0; and any T, any N, M-1.
Only patients followed for at least 5 years and with all
TNM factors coded according to 3rd and 4th edition
AJCC definitions were included in this analysis. No
 particular surgical treatment appeared to generate
compellingly superior 5-year survival, but we expect
this to change with longer follow-up. However, even
with the large number of total cases some subsets were
problematically small. Cases accessioned between
1985-1988 usually were staged according to the 2nd
edition of the AJCC staging system, and because of
incompatibility with the 3rd and 4th edition staging
system, could not be included in this analysis. It is for
this reason we report only 5-year stage-stratified
survival rates despite our possession of 10-year data.
Table 7. Five-Year Relative Survival Rates of Papillary Thyroid Carcinoma Patients Diagnosed
between 1985-1990 by AJCC TNM Status (3rd edition) and Type of Surgery

Type of surgery

Total wit
Near- Total w/o Total with
TNM None/unknown Lobectomy rad/mod
totala(No.) LNDb (No.) LNDc (No.)
status (No.) % (No.) % LNDd(No
% % %
%

AJCC: American Joint Committee on Cancer; w/o: without; LND: lymph node dissection; rad: radical; mod: modified.
a
Near-total thyroidectomy.
b
Total thyroidectomy without lymph node dissection.
c
Total thyroidectomy with limited lymph node dissection.
d
Total thyroidectomy with radical or modified lymph node dissection.

No. of 115 828 481 622 249 64

cases

T=1
 Type of surgery

Total wit
Near- Total w/o Total with
TNM None/unknown Lobectomy rad/mod
totala(No.) LNDb (No.) LNDc (No.)
status (No.) % (No.) % LNDd(No
% % %
%

N=0 92.6 100 100 99.7 99.5 95.7

M=0

No. of 56 126 183 205 179 165

cases

T=4

N=0 85.0 90.9 92.6 99.0 94.9 91.2

M=0

No. of 250 1594 1178 1672 661 192

cases

Any T

N=0 94.2 100 99.0 99.8 99.2 96.5

M=0
 Type of surgery

Total wit
Near- Total w/o Total with
TNM None/unknown Lobectomy rad/mod
totala(No.) LNDb (No.) LNDc (No.)
status (No.) % (No.) % LNDd(No
% % %
%

No. of 201 298 456 289 760 600

cases

Any T

N=1 96.6 98.4 99.0 93.2 99.3 100

M=0

No. of 458 1984 1643 2052 1340 734

cases

Any T

Any N 100 100 99.9 100 100 100

M=0

No. of 31 39 48 81 59 52
cases

Any T
 Type of surgery

Total wit
Near- Total w/o Total with
TNM None/unknown Lobectomy rad/mod
totala(No.) LNDb (No.) LNDc (No.)
status (No.) % (No.) % LNDd(No
% % %
%

Any N 63.0 78.0 82.2 74.5 84.6 95.3

M=1

Table 8. Five-Year Relative Survival Rates of Patients with Follicular Thyroid Carcinoma
Diagnosed between 1985-1990, by AJCC TNM Status (3rd edition) and Type of Surgery

Type of surgery

Total wit
Near- Total w/o Total with
TNM None/unknown Lobectomy rad/mod
totala(No.) LNDb (No.) LNDc (No.)
status (No.) % (No.) % LNDd(No
% % %
%

AJCC: American Joint Committee on Cancer; w/o: without; LND: lymph node dissection; rad: radical; mod: modified.
a
Near-total thyroidectomy.
b
Total thyroidectomy without lymph node dissection.
c
Total thyroidectomy with limited lymph node dissection.
d
Total thyroidectomy with radical or modified lymph node dissection.

No. of 16 129 61 70 28 6
cases

T=1
 Type of surgery

Total wit
Near- Total w/o Total with
TNM None/unknown Lobectomy rad/mod
totala(No.) LNDb (No.) LNDc (No.)
status (No.) % (No.) % LNDd(No
% % %
%

N=0 99.5 100 96.6 91.7 100 102

M=0

No. of 7 38 26 41 21 10
cases

T=4

N=0 96.3 93.6 84.0 82.4 91.8 19.7

M-0

No. of 48 407 233 373 112 26

cases

Any T

N=0 88.0 96.4 92.4 95.0 100 90.5

M=0
 Type of surgery

Total wit
Near- Total w/o Total with
TNM None/unknown Lobectomy rad/mod
totala(No.) LNDb (No.) LNDc (No.)
status (No.) % (No.) % LNDd(No
% % %
%

No. of 16 15 23 18 31 26
cases

Any T

N=1 50.9 87.7 94.8 82.8 82.6 57.7

M=0

No. of 62 458 259 380 135 46

cases

Any T

Any N 88.3 98.3 93.9 97.6 95.3 80.3

M=0

No. of 20 11 16 35 9 10
cases

Any T
 Type of surgery

Total wit
Near- Total w/o Total with
TNM None/unknown Lobectomy rad/mod
totala(No.) LNDb (No.) LNDc (No.)
status (No.) % (No.) % LNDd(No
% % %
%

Any N 23.6 48.4 49.9 53.1 99.3 57.1

M=1

Similar analyses also were attempted for each of the

categories of treatment listed in Table 4, but overly
small subsets precluded meaningful survival analysis.
Of the many non-TNM prognostic models offered for
differentiated thyroid carcinoma, perhaps the easiest to
apply is that offered by Cady et al., the AMES
system.5 Because "major capsular invasion" versus
"minor capsular invasion" by follicular carcinoma
constitutes a criterion for division into "high risk"
versus "low risk" cases according to this system and
because the NCDB data set fails to code this, the
AMES system could not be evaluated for follicular
cases. Figure 5(5K) summarizes results for 5-year
survival of the AMES "high risk" (6.4%) versus AMES
"low risk" (93.6%) papillary thyroid carcinoma cases.
This figure is based on the 9369 cases for which both
5-year follow-up and all factors for AMES calculations
were available.
 Figure 5.
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Relative survival of thyroid carcinomas diagnosed between
1985-1990 by AMES risk levels.
Other Histologies
Figure 6 (5K) documents that 5-year survival for
patients with Hrthle cell carcinoma closely parallels
that of follicular cases, thus supporting the popular
view that Hrthle cell carcinoma simply is a variant of
follicular carcinoma. However, disparate 10-year
overall survival was noted (76% vs. 85%).
 Figure 6.
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Relative survival of Hrthle cell thyroid carcinomas
diagnosed between 1985-1990 and staged according to the
3rd/4th editions of the American Joint Committee on Cancer
(AJCC) staging system.
Figure 7 (5K) shows 5-year relative survival for cases of
medullary carcinoma. The NCDB data set does not
contain a separate item for distinguishing familial from
sporadic cases.
 Figure 7.
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Relative survival by AJCC stage of medullary thyroid
carcinomas diagnosed between 1985-1990 and staged
according to the 3rd/4th editions of the American Joint
Committee on Cancer (AJCC) staging system.
All cases of undifferentiated/anaplastic carcinoma are,
by definition, Stage IV. Figure 2 (8K) summarizes 10-
year relative survival for these patients. Age < 45 years
and small tumor size (and possibly the absence of
extrathyroidal spread) appear overrepresented among
those patients surviving 5 years.
DISCUSSION
To our knowledge, this 1985-1995 cohort of 53,856
thyroid carcinoma cases represents the largest
contemporaneous, stage-stratified series yet reported.
The ability of a national, community-based, electronic
registry system such as the NCDB to collect large
numbers of patients with rare tumors such as thyroid
carcinoma constitutes yet another virtue of this cost-
effective benchmarking system. As diagnostic methods,
imaging techniques, and treatment paradigms shift over
time, stage distribution, patterns of care, and outcomes
can be expected to shift, hence the importance of using
contemporaneous data for cancer benchmarking.
The number of patients followed for 5 years and
available for stage-stratified analysis was undermined
by the change in AJCC staging for this site, which
occurred with publication of the 3rd edition of the
AJCC manual in 1988. Reliable conversion of cases
staged according to the previous edition was not
feasible given the NCDB's current data set. Hence, only
cases staged according to 3rd/4th edition definitions
were used in reporting stage-stratified results. It is for
this reason we can offer only 5-year stage-stratified
results despite 10 years of data.
Some factors for this site remained relatively stable
over time. Gender distribution, ethnic distribution, and
income level distribution previously have been
discussed in an article devoted to describing NCDB
cases accessioned in 1992.20 Briefly, females
predominate for all histologies: papillary (74%),
follicular (74%), medullary (62%), and
undifferentiated/anaplastic (64%). Ethnic distribution
of papillary and follicular thyroid carcinoma roughly
paralleled that for the NCDB as a whole; however, case
ratios for Hispanics and Asians appeared slightly
higher than expected. The lack of significant change in
these items dissuaded us from reiterating findings
already described in the previous report.
Although the majority of clinicians recognize the effect
of age on the prognosis of patients with follicular and
papillary thyroid carcinoma, these NCDB data suggest
an effect on other thyroid histologies as well. The
effect of this factor on prognosis for medullary and
undifferentiated/anaplastic thyroid carcinoma appears
to be noteworthy.
Risk models derived from one population, particularly
if that population shares certain characteristics (e.g., all
treated at one institution, from one geographic region,
from one organization, treated in distant past, etc.),
may not predict outcomes for a different
population.21Hence, national data such as those
described here assumes particular importance in
assessing various prognostic models. A number of
different prognostic models have been proposed for
patients with "differentiated thyroid carcinoma" (i.e.,
papillary or follicular): the AMES system,5 the AGES
system,8, 9 the MACIS system,10 the Clinical Class
system,11 the Mazzaferri system,12 the GAMES
system,22 and, of course, the TNM system.6, 16, 17 In
all these models, a relatively small proportion of
patients fit into the higher risk subgroup(s). The
superimposable survival curves for AJCC TNM Stages
I and II for papillary and follicular thyroid carcinomas
in this series suggests an possible opportunity for
simplifying the current TNM prognostic system further.
Unfortunately, certain elements of other prognostic
systems were either not yet included in the 1985-1995
NCDB data set (e.g., ploidy, degree of capsular
invasion, etc.) or not yet reported consistently by
pathologists (e.g., grading as utilized in the Mayo
Clinic AGES system). This fact makes evaluating these
systems using NCDB data problematic. However, we
were able to evaluate the AMES system as it applied to
cases of papillary thyroid carcinoma, and found the
survival differences between "high risk" and "low risk"
groups consistent with the earlier report by Cady and
Rossi.5 Additional data elements collected as part of an
ACoS Patient Care Evaluation Study of thyroid
carcinoma cases diagnosed in 1996 should facilitate
evaluation of other prognostic models in the future.
Although total thyroidectomy remains the standard for
patients with medullary carcinoma,23 the surgical
treatment of papillary and follicular ("differentiated")
thyroid carcinoma remains controversial.23, 24 Initial
autopsy studies suggesting a very high degree of
pathologically confirmed contralateral disease
supported the routine use of total
thyroidectomy.25 However, the significance of this
finding became suspect when autopsy studies in the
U.S. showed a high incidence (3-6%) of asymptomatic,
occult, intraglandular foci of this clinically rare tumor
(with world standard reported incidence rates of usually
2-5 per 100,000 population) in patients dying of other
causes,26 and a very high autopsy incidence (14-24%)
when glands were analyzed using fine step-sectioning
techniques.27, 28 A large clinical series from the
Memorial Sloan-Kettering Cancer Center (MSKCC)
with 20-year follow-up revealed excellent results (i.e.,
99% 20-year survival and only 4% local recurrence)
associated with the treatment of patients with favorable
prognostic factors (defined as "low risk" according to
the MSKCC classification) by complete ipsilateral
lobectomy and isthmectomy and long term hormonal
suppression.29 Other series with long follow-up, using
different risk group definitions, also have supported the
selective use of complete lobectomy rather than routine
total thyroidectomy.9 These findings echo those of
smaller, earlier studies.30-32 However, other major
studies document fewer recurrences and lower
mortality for patients treated with total/near-total
thyroidectomy and I-131.6, 11, 12 The multiplicity of
risk stratification schemes (with varying definitions of
"low risk," "favorable prognosis," etc.), the variable use
of I-131, and variable practice with respect to long term
hormonal suppression complicate a stratified analysis
of treatment-related outcomes. Because complications
with lobectomy are lower than with total
thyroidectomy,33 because effective salvage therapy in
the presence of recurrence in the opposite lobe is
possible, and because mortality has been shown by
multiple studies to be low, several experts recommend
that patients at low risk for recurrence initially be
treated with simple lobectomy-isthmectomy and long
term hormonal suppression.5, 9, 10, 29
These NCDB data provide a snapshot of current
surgical opinion concerning the "lobectomy versus
total" controversy. Overall, only 18% of patients with
papillary carcinoma and 25% of patients with follicular
carcinoma are treated by ipsilateral lobectomy. Even
for patients with T1N0M0 tumors, only 35% of patients
with papillary carcinoma and 42% of patients with
follicular carcinoma are so treated.
Tables 7 and 8 document that, with 5 years of follow-
up, more extensive surgical resection fails to generate
convincingly superior survival for any subgroup.
Naturally, given the indolence of this disease,
prolonged follow-up is required for a true assessment
of the survival impact of variation in surgical treatment.
The NCDB data set fails to include descriptions of the
dose and frequency of I-131 treatments, but confirms
that such treatments are used rarely as the primary
therapeutic modality. Similarly, the NCDB data set
fails to include details of adjuvant hormonal
suppression with thyroid hormone. The aforementioned
ACoS Patient Care Evaluation Study of thyroid
carcinoma cases diagnosed in 1996 will examine care
patterns and outcomes with respect to I-131 and
hormonal suppression.
Five-year, stage-stratified relative survival curves for
patients with Hrthle cell carcinoma appear similar to
those for patients with follicular neoplasms, thus
lending support to the widely held contention that these
histologic types behave similarly.34 The World Health
Organization and the majority of pathologists classify
Hrthle cell neoplasms as a variant of follicular
neoplasms.26However, the 9% difference in survival at
10 years (76% for Hrthle cell carcinoma vs. 85% for
follicular carcinoma), emphasizes the hazard of
generalizing based on 5-year results for this indolent
tumor, and prognosis indeed may be worse.
The majority of authorities recommend total
thyroidectomy for patients with medullary carcinoma
of the thyroid.23, 35, 36 The vast majority of patients
in this NCDB cohort were treated by total
thyroidectomy, and only 8.9% of patients were treated
by ipsilateral lobectomy.
Previous series of patients with
undifferentiated/anaplastic carcinoma of the thyroid
document occasional long term survivors, but the
overall prognosis remains dismal. Survivors appear
primarily to be patients with completely resected, small
areas of anaplastic carcinoma, often within areas of
differentiated thyroid carcinoma.37 True assessment of
the volume or size of an area of anaplastic
transformation in such cases is difficult. The fact that
48% of NCDB patients receive no primary surgical
treatment implies that the majority of patients with this
diagnosis are judged to have incurable disease.
However, the 14% 10-year relative survival rate of
NCDB patients, and the plateau of the survival curve,
document that occasional cases can be cured. The 55%
5-year relative survival of patients age < 45 years,
admittedly based on few patients, encourages
speculation that a definable subgroup of patients with
undifferentiated/anaplastic thyroid carcinoma might
perhaps be viewed as curable. Independent pathology
review certainly would be desirable with respect to
these 5-year survivors with anaplastic carcinoma, but
the NCDB does not yet have a workable mechanism for
doing this.
The NCDB currently accessions nearly 60% of incident
cancers in the U.S. Though a new linkage with the
COC Approvals Program, an 80% accession rate for
1998 is predicted. In contrast, the population-based
Surveillance, Epidemiology, and End Results system,
used for estimating U.S. cancer incidence rates,
accessions approximately 14% of incident cancers and,
judging from U.S. census data, is neither racially nor
geographically representative of the current U.S.
population.13A joint initiative by the ACS and the
ACoS to add a population-based component to the
NCDB currently is being explored. Such a component
would permit the NCDB to track cancer incidence as
well as care patterns and treatment outcomes. In the
context of thyroid carcinoma, such a national system
might prove useful in monitoring health effects
attributable to I-131 contamination from U.S.
atmospheric nuclear testing in the 1950s, a topic
recently addressed by the National Cancer
Institute,38, 39 and other projects.
The aforementioned ACoS Patient Care Evaluation
(PCE) Study of thyroid carcinoma cases diagnosed in
1996 recently completed accrual and baseline data will
be reported within a year. The study includes data
items not included in the NCDB data set and should
help answer some questions left unaddressed by this
study (e.g., the effect of I-131 ablation and subsequent
I-131 therapy and hormonal suppression). We currently
plan to track the 1996 PCE cohort of patients
prospectively over the next 20-30 years using the
NCDB.
Conclusions
Overall 10-year relative survival for patients with
papillary thyroid carcinoma is 93% and is 85% for
patients with follicular thyroid carcinoma. Although 5-
year overall and stage-stratified relative survival for
patients with Hrthle cell carcinoma closely matches
that of patients with follicular carcinoma, overall
survival at 10 years is 9% lower, suggesting a
marginally worse prognosis.
At 5 years, the current AJCC TNM staging system fails
to prognostically discriminate between Stage I and
Stage II papillary carcinoma patients and between
Stage I and Stage II follicular carcinoma patients.
Should this observation hold over time, a simplification
of the current AJCC staging system may be warranted.
Total thyroidectomy lymph node sampling/dissection
represents the dominant method of surgical treatment
rendered to patients with papillary and follicular
neoplasms. Approximately 38% of such patients
receive I-131 ablation/therapy. Only 2-3% of such
patients are treated with I-131 alone. At 5 years,
patients with T-1 N-0 M-0 disease (as well as patients
with Stage I and Stage II disease) survive comparably
whether treated by simple lobectomy or by more
extensive procedures. The lack of compelling
treatment-related differences in survival for patients
with more advanced disease emphasizes the importance
of longer follow-up for patients with these neoplasms.
Such reports currently are planned. With longer follow-
up, the survival impact of variations in treatment
should become detectable.
Age at diagnosis appears to influence the prognosis of
not only patients with papillary, follicular, and Hrthle
cell carcinomas, but the prognosis of patients with
medullary and undifferentiated/anaplastic carcinomas
as well.
The 14% 10-year relative survival of patients with
undifferentiated/anaplastic carcinoma, the plateau of
the survival curve, and the 55% 5-year relative survival
of patients age < 45 years at time of diagnosis suggest
that a subset of these patients may be cured of their
disease.
The NCDB system permits analysis of care patterns
and survival for large numbers of contemporaneous
U.S. patients with rare neoplasms such as thyroid
carcinoma. In this context, it represents an unsurpassed
clinical tool for analyzing care, evaluating prognostic
models, generating new hypotheses, and overcoming
the volume-related drawbacks inherent in the study of
such neoplasms.