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ORIGINAL RESEARCH
The changing face of thyroid cancer in a population-based
cohort
K. Alok Pathak
1,3
, William D. Leslie
2
, Thomas C. Klonisch
3
& Richard W. Nason
1
1
Head and Neck Surgical Oncology, Cancer Care Manitoba, Winnipeg, Canada
2
Nuclear Medicine, Cancer Care Manitoba, Winnipeg, Canada
3
Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada
Keywords
Anaplastic, epidemiology, incidence,
outcome, survival, trend
Correspondence
K. Alok Pathak, University of Manitoba, Head
and Neck Surgical Oncologist, Cancer Care
Manitoba, GF 440 A, 820 Sherbrook Street,
Winnipeg R3A 1R9, Canada.
Tel: +1-204-787-8040; Fax: +1-204-787-2768;
E-mail: alok.pathak@cancercare.mb.ca
Funding Information
This study was supported by the University of
Manitoba Research Grant and the
Department of Surgery, University of
Manitoba Research Grant.
Received: 2 April 2013; Revised: 21 May
2013; Accepted: 30 May 2013
doi: 10.1002/cam4.103
Abstract
In North America, the incidence of thyroid cancer is increasing by over 6% per
year. We studied the trends and factors influencing thyroid cancer incidence, its
clinical presentation, and treatment outcome during 1970–2010 in a population-
based cohort of 2306 consecutive thyroid cancers in Canada, that was followed
up for a median period of 10.5 years. Disease-specific survival (DSS) and
disease-free survival were estimated by the Kaplan–Meier method and the inde-
pendent influence of various prognostic factors was evaluated by Cox propor-
tional hazard models. Cumulative incidence of deaths resulting from thyroid
cancer was calculated by competing risk analysis. A P-value <0.05 was considered
to indicate statistical significance. The age standardized incidence of thyroid can-
cer by direct method increased from 2.52/100,000 (1970) to 9.37/100,000 (2010).
Age at diagnosis, gender distribution, tumor size, and initial tumor stage did not
change significantly during this period. The proportion of papillary thyroid
cancers increased significantly (P<0.001) from 58% (1970–1980) to 85.9%
(2000–2010) while that of anaplastic cancer fell from 5.7% to 2.1% (P<0.001).
Ten-year DSS improved from 85.4% to 95.6%, and was adversely influenced by
anaplastic histology (hazard ratio [HR] =8.7; P<0.001), male gender
(HR =1.8; P=0.001), TNM stage IV (HR =8.4; P=0.001), incomplete surgi-
cal resection (HR =2.4; P=0.002), and age at diagnosis (HR =1.05 per year;
P<0.001). There was a 373% increase in the incidence of thyroid cancer in
Manitoba with a marked improvement in the thyroid cancer-specific survival
that was independent of changes in patient demographics, tumor stage, or treat-
ment practices, and is largely attributed to the declining proportion of anaplastic
thyroid cancers.
Introduction
Thyroid cancer is the most common malignant endocrine
tumor and is the seventh most common cancer seen in
Canadians with an estimated 5650 new thyroid cancers
diagnosed in 2012 [1]. In Canada, the incidence of thy-
roid cancer is increasing more rapidly than any other
cancer; by 6.8% per year in Canadian males (1998–2007)
and by 6.9% per year in Canadian females (2002–2007)
[1]. Similar trends have been reported globally [2–13]. By
direct method, the age standardized incidence rate (ASIR)
of thyroid cancer per 100,000 Canadians has increased
from 1.1 in 1970–1972 to 6.1 in 2012 for males, and from
3.3 to 22.2 in females during the same period [1, 14].
The trends in the United States (US) mirror that of Can-
ada with a threefold increase in the incidence of thyroid
cancer from 4.85/100,000 in 1975 to 14.25/100,000 in
2009 and an annual percent increase (2000–2009) of 6.0%
for the US males and 6.9% for the US females [15]. The
age and delay adjusted incidence rate of thyroid cancer
between 2006 and 2010 was 6.1/100,000 for the US males
and 18.2/100,000 for the US females using joint point
regression program. An estimated 56,460 new cases of
thyroid cancers are likely to be seen in the US in 2012
and 1780 will die from it. The life time probability of
developing a thyroid cancer for a Canadian female is 1 in
ª2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the
Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided
the original work is properly cited.
1
Cancer
Medicine Open Access
71 (1.4%) but only 1 in 1374 (0.1%) will actually die
from it [16]. Canadian males have a lower life time risk
of developing thyroid cancer at 1 in 223 (0.4%) with the
risk of death from thyroid cancer at 1 in 1937 (0.1%).
Although the incidence of thyroid cancer has been
rising, it had an excellent 5-year relative survival ratio
of 98% in 2011 [16]. Thyroid cancers represent a con-
glomerate of different histological types that have diverse
clinical behavior. Differentiated thyroid cancers (papillary
and follicular) typically have an excellent survival, whereas
poorly differentiated and anaplastic thyroid cancers have
a very poor outcome. Although the time trends in the
incidence of thyroid cancer in Canada have been reported
earlier [14, 17], little has been recorded about the trends
in outcome of thyroid cancer in a population cohort. The
objective of this study was to assess the trends in the inci-
dence, clinical presentation, treatment practices, and dis-
ease outcome of thyroid cancer in a population-based
cohort spanning four decades from 1970 to 2010.
Patients and Methods
Study group
Manitoba thyroid cancer cohort is a historical cohort that
includes all 2306 consecutive thyroid cancers observed in
2296 patients in the province of Manitoba, Canada, from
1 January 1970 to 31 December 2010, as registered in the
Manitoba Cancer Registry. The Manitoba Cancer Registry
is a member of the North American Association of Cen-
tral Cancer Registries which administers a program that
reviews member registries for their ability to produce
complete, accurate, and timely data. CancerCare Mani-
toba is the sole comprehensive cancer care center in the
province where all the cancer patients from the province
are primarily referred and the Manitoba Cancer Registry
is a part of CancerCare Manitoba. Ethics approval for this
study was obtained from the Research Ethics Board at the
University of Manitoba.
We reviewed individual electronic and paper records of
diagnosis and treatment for this cohort of patient. The
primary source of diagnostic information included 2148
pathology reports, 80 discharge summaries, 56 autopsy
records, 18 operative reports, and 4 death certificates.
ASIR was calculated by direct method (1). Age-specific
incidence rates were initially calculated by using the age
distributions of the newly diagnosed thyroid cancers cases
in the province and that of the provincial population for
each year obtained from the Manitoba Health’s popula-
tion registry, Manitoba Bureau of Statistics [18] and Sta-
tistics Canada [19]. Age-specific incidences were then
applied to the 1991 standard Canadian population [1] to
calculate the ASIR per 100,000 population.
Patient demographics, extent of disease at initial pre-
sentation; the treatment modalities employed; pathology
details; cancer recurrences during follow-up and final out-
come status as of 1 January 2013 were recorded. All
patients who migrated out of province (considered lost to
follow-up) or died during the study period, were censored
at that point in time. All cases were restaged according to
the American Joint Cancer Committee/Union Internatio-
nale Contre le Cancer (AJCC/UICC) staging for thyroid
cancer (7th edition, 2009); the topography and the histol-
ogy were recoded by WHO International Classification of
Diseases for Oncology (3rd Edition) codes and the dis-
ease, signs, and symptoms by International Classification
of Diseases (10th edition) codes to ensure uniformity.
The pathology and treatment details of 683 (29.6%) were
independently reviewed for accuracy as a part of a collab-
orative staging project.
Statistical analysis
Analysis of variance was used to compare group means,
and categorical data were compared using the Pearson
chi-square test with continuity correction, as appropriate.
AP-value <0.05 was considered to indicate statistical sig-
nificance and 95% confidence intervals were used to
express reliability in the estimates. After checking for nor-
mality assumption the mean and standard deviation were
used to express normally distributed data (such as age of
the patients) and median with interquartile range were
used for nonnormally distributed data (such as tumor size
and follow-up). The data were managed and analyzed
using SPSS for Windows version 20.0 (SPSS Inc., Chi-
cago, IL). Disease-free survival (DFS) and disease-specific
survival (DSS) were estimated by the Kaplan–Meier prod-
uct limit method, and the effect of individual prognostic
factors on survival was assessed by using the log rank test.
Multivariate analyses were performed with Cox propor-
tional hazard models to assess the independent effect of
prognostic factors on DSS after testing for the propor-
tional hazard assumption. The competing influence of
other causes of mortality, such as death due to a second
primary tumor or noncancer deaths, was analyzed by
competing risk regression model using STATA version 12
(StataCorp. TX).
Results
Study cohort
In total, 2306 thyroid cancers were observed in Manitoba
in 2296 patients from 1970 to 2010. Nine patients had a
synchronous second primary tumor of a different histo-
logy along with papillary thyroid cancer (follicular-3,
2ª2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
The Changing Face of Thyroid Cancer K. A. Pathak et al.
h€
urthle cell-3, medullary-2, poorly differentiated-1), while
one patient had a metachronous second papillary carci-
noma in the contra-lateral thyroid lobe 25 years after ini-
tial management. According to 2011 census, the
population of Manitoba was recorded at 1,208,268 that
increased by an average of 0.56% per year from 1970 level
of 988,245. The number of newly diagnosed thyroid can-
cers increased from 22 in 1970 to 122 in 2010, and the
ASIR per 100,000 for thyroid cancer from 2.52 (95% con-
fidence interval [CI] =1.57–3.83) in 1970 to 9.37 (95%
CI =7.65–11.08) in 2010 (Fig. 1). The ASIR per 100,000
rose from 0.72 (95% CI =1.57–3.83) in 1970 to 4.94
(95% CI =3.35–7.03) in 2010 for males and the respec-
tive rates for females went up from 4.28 (95% CI =2.56–
6.71) to 13.75 (95% CI =10.96–17.04). The ASIR per
100,000 for anaplastic thyroid cancers fell from 0.11 (95%
CI =0.05–0.19) during 1970–1980 to 0.05 (95%
CI =0.02–0.11) in 2001–2010 for both sexes and the
respective rates for papillary thyroid cancer went up from
0.93 (95% CI =0.75–1.15) to 6.64 (95% CI =6.17–7.11).
The Manitoba thyroid cancer cohort included 570
(24.8%) males and 1726 (75.2%) females with a mean age
(standard deviation) of 49 18 years. The mean age
of patients at the time of diagnosis, median tumor size,
and the tumor stage at presentation showed statistically
nonsignificant change (P>0.05, NS) over the past four
decades (Table 1). Thyroid cancers ≤10 mm (micro-
carcinoma) represented 23.4% of all thyroid cancers and
this proportion did not change significantly (P=0.87)
during the study period. Lymph node involvement was
present in 23.7% cases and distant metastasis in 3.9% cases
at the time of diagnosis. Multifocal disease was observed in
32.3% cases, gross extrathyroidal extension of tumor in
20.9% cases, and complete surgical excision of gross
tumor was achieved in 96.1% cases. The distribution of
T stage (P=0.50), N stage (P=0.27), and M stage
(P=0.61) as well as the proportion of patients with mul-
tifocal disease (P=0.26), gross extrathyroidal extension
of tumor (P=0.66) or with complete excision of tumor
(P=0.40) remained unchanged during the study period.
Papillary thyroid cancer was the most common histo-
logical type, and the proportion of papillary thyroid can-
cers steadily increased from 58.0% (1970–1980) to 85.9%
(2000–2010). Most of the thyroid cancers were classical
papillary thyroid cancers (46.9%), followed by follicular
(24.2%), encapsulated (2.3%), and microinvasive (1.6%)
variants. Sclerosing, solid, tall cell, and columnar cell vari-
ants together accounted for only 1.9% of all thyroid can-
cers. During the same period, the proportion of all
thyroid cancers that were diagnosed as follicular variants
of papillary thyroid cancer increased from 12.4% to
32.9% (Table 1), whereas the proportion of follicular car-
cinoma fell from 26% to 5.1% (P<0.001) and anaplastic
carcinoma from 5.7% to 2.1% (P<0.001). The propor-
tion of medullary thyroid carcinoma has remained nearly
unchanged. Total thyroidectomy was performed in 55.1%
cases and 34.8% had adjuvant radioactive iodine (RAI).
The percentage of the patients undergoing total thyroid-
ectomy increased by two and a half times between 1970
and 1980 and 2001–2010 (P<0.001) while those receiv-
ing adjuvant RAI increased by over five times
(P=0.004).
Oncological outcome of thyroid cancer
In all, 201 patients died from thyroid cancer (case fatality
rate 8.8%). The case fatality rate for different histological
types of thyroid cancer is summarized in Table 2. Of all
deaths due to thyroid cancer, 63 (31.3%) had papillary
carcinoma, 60 (29.9%) anaplastic, 24 (11.9%) follicular,
21 (10.4%) medullary, 15 (7.5%) h€
urthle cell, 8 (4%)
poorly differentiated, and 10 (5%) had unspecified thy-
roid carcinoma. The 10-year DSS of Manitoba thyroid
cancer cohort (N=2296) was 91.8% (95% CI =90.5–
92.9%), which improved significantly from 85.4% (1970–
1980) to 95.6% (2001–2010) (Table 1). Tumor histology
had a very significant impact on the DSS and DFS surviv-
als (Table 2). Papillary thyroid cancer had the best DSS
rates (96.8% at 10 years and 94.6% at 20 years), whereas
only 7.3% with anaplastic cancer survived for 10 years.
The cumulative incidence function (CIF) by competing
risk regression analysis (Fig. 2) shows an 8.1% reduction
(from 12.6% to 4.5%) in death due to thyroid cancer at
10 years of follow-up.
Treatment outcomes were assessed in the 2065 patients
who underwent primary surgical treatment with radical
100
Logarithmic scale
Year of diagnosis
Incidence per 100,000
Number of new thyroid cancers
1970 1975 2000 2010200519951985 19901980
10
1
Figure 1. Trends in the age standardized incidence, the number of
newly diagnosed thyroid cancers in Manitoba, Canada (1970–2010).
ª2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. 3
K. A. Pathak et al. The Changing Face of Thyroid Cancer
intent in Manitoba; after excluding cases that were
diagnosed only on autopsy or death report (n=60),
those who died before surgery (n=64), nonsurgical can-
didates (n=35) or those who refused treatment
(n=24), and if primary surgery or follow-up performed
in another province/country (n=48). During median fol-
low-up of 10.5 years (interquartile range =4.8–
18.8 years), 78 (3.8%) patients had posttreatment residual
disease and another 200 (9.7%) patients had recurrence
of disease at least 6 months after successful initial treat-
ment. The recurrences were in the residual thyroid lobe
or thyroid bed in 23 (11.5%) cases, in the central com-
partment of neck in 64 (32%), in the lateral compartment
of neck in 44 (22%), at a distant metastatic site in 54
(27%), and at multiple sites in 15 (7.5%) cases. Ten-year
DFS of the surgically treated patients was 89.3% (95%
Table 1. Clinical characteristics of thyroid cancer by decade of presentation.
1970–1980
(N=331)
1981–1990
(N=410)
1991–2000
(N=594)
2001–2010
(N=971) P-value
Mean age in years 49.3 18.4 47.5 18.6 48.0 18.7 49.1 17.0 0.14 (NS)
Gender ratio (female:male) 2.5:1 2.8:1 3.6:1 3:1 0.45 (NS)
Median tumor size (interquartile range) 19.9 (15–22) mm 20 (20–25) mm 21 (20–24) mm 20 (19–22) mm 0.44 (NS)
Tumor size distribution
≤1 cm 75 (22.6%) 117 (28.5%) 153 (25.8%) 242 (24.9%) 0.13 (NS)
1–2 cm 110 (33.2%) 93 (22.7%) 143 (24.1%) 247 (25.5%)
2–4 cm 108 (32.6%) 152 (37.0%) 197 (33.1%) 310 (31.9%)
>4 cm 38 (11.6%) 48 (11.8%) 101 (17.0%) 172 (17.7%)
Stage I 207 (62.6%) 280 (68.4%) 380 (64.0%) 610 (62.8%) 0.22 (NS)
Stage II 23 (6.9%) 34 (8.3%) 62 (10.4%) 120 (12.4%)
Stage III 32 (9.7%) 52 (12.6%) 62 (10.4%) 125 (12.9%)
Stage IV 69 (20.8%) 44 (10.7%) 90 (15.2%) 116 (11.9%)
Total thyroidectomy 94 (28.4%) 159 (38.9%) 293 (49.3%) 691 (71.2%) <0.001
Adjuvant radioactive iodine 36 (10.9%) 79 (19.3%) 177 (29.8%) 603 (62.1%) 0.004
Histology
Papillary (%) 192 (58.0%) 278 (67.8%) 459 (77.3%) 834 (85.9%) <0.001
Follicular (%) 86 (26.0%) 70 (17.1%) 62 (10.4%) 50 (5.1%)
H€
urthle cell (%) 3 (0.9%) 24 (5.9%) 22 (3.7%) 36 (3.7%)
Poorly differentiated (%) 9 (2.7%) 1 (0.2%) 3 (0.5%) 3 (0.3%)
Medullary (%) 17 (5.1%) 24 (5.9%) 17 (2.9%) 21 (2.2%)
Anaplastic (%) 19 (5.7%) 9 (2.2%) 24 (4.0%) 20 (2.1%)
Unspecified (%) 5 (1.5%) 4 (1%) 7 (1.2%) 7 (0.7%)
Median follow-up in months (95% CI) 419.4 (409.9–428.9) 304.9 (296.2–313.7) 188.4 (182.5–194.3) 68.5 (65.4–71.6) <0.001
10 year DSS (N=2296) 85.4 (82.9-90.0)% 92.2 (89.1–94.5)% 89.3 (86.5–91.6)% 95.6 (90.5–96.6)% <0.001
Posttreatment 10 year DFS (N=2065) 86.6 (81.1–90.6)% 88.9 (85.1–91.8)% 88.1 (84.7–90.6)% 91.9 (89.2–94.1)% 0.18 (NS)
Table 2. Case fatality rate and survival by histological types of thyroid cancers.
Case fatality rate 10 year DSS (95% CI) 20 year DSS (95% CI) 10 year DFS (95% CI) 20 year DFS (95% CI)
Papillary 3.6% 96.8 (95.7–97.7)% 94.6 (92.9–95.9)% 87.7 (85.9–89.4)% 84.8 (82.5–86.9)%
Follicular 9.0% 91.5 (87.0–94.5)% 88.6 (83.1–92.4)% 87.3 (82.4–91.0)% 86.1 (80.8–90.0)%
H€
urthle cell 17.6% 81.4 (69.7–89.0)% 75.6 (61.2–85.2)% 69.8 (57.9–79.0)% 69.8 (57.9–79.0)%
Poorly differentiated 31.2% 74.1 (28.9–93.0)% 74.1 (28.9–93.0)% 27.3 (6.5–53.9)% 27.3 (6.5–53.9)%
Medullary 26.9% 77.6 (65.4–85.9)% 62.6 (47.5–74.5)% 52.0 (38.5–63.9)% 43.1 (28.9–56.6)%
Anaplastic 83.3% 7.3 (2.4–15.9)% 7.3 (2.4–15.9)% 1.4 (0.1–6.7)% 1.4 (0.1–6.7)%
1970–1980 1981–1990
1991–2000 2001–2010
0
0
0.05
Proportional cumulative incidence
0.1
0.15
12 24 36 48 60
Months after diagnosis
72 84 96 108 120
Figure 2. Cumulative incidence of death resulting from thyroid
cancer over 10 years.
4ª2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
The Changing Face of Thyroid Cancer K. A. Pathak et al.
CI =87.7–90.8%) that has not changed significantly over
the last four decades (Table 1).
On multivariate analysis by Cox proportional hazard
model, DSS was adversely influenced independently by
nonpapillary histology especially anaplastic (hazard ratio
[HR] =8.7; 95% CI =5.2–14.5; P<0.001), male gender
(HR =1.8; 95% CI =1.3–2.5; P=0.001), TNM stage III
(HR =2.30; 95% CI =1.00–5.29, P=0.05), and IV
(HR =8.37; 3.99–17.54, P<0.001), incomplete surgical
resection (HR =2.4; 95% CI =1.4–4.2, P=0.002), and
age at diagnosis (HR =1.05 per year; 95% CI =1.03–
1.06; P<0.001). Each of these factors, except the histo-
logy has remained unchanged during the study period
(Table 1). The extent of thyroidectomy, use of adjuvant
RAI, or the decade of diagnosis did not have any
significant influence on DSS (Table 3). Competing risk
subhazard model confirmed these observations of Cox
regression analysis.
Discussion
A cohort is a population group, or subset thereof, that is
followed over a period of time. The members of the
cohort, based on defined criteria, share common experi-
ence which in this study was diagnosis of thyroid cancer
in the province of Manitoba. By virtue of the residence in
the same province our study cohort was expected to share
similar risk of exposure and get similar standard of medi-
cal care in the publicly funded health care system of the
province. The incidence trends of thyroid cancers in the
US were reported by using the Surveillance, Epidemiol-
ogy, and End Results (SEER) database, which is robust
but it has its inherent limitations in terms of coverage,
coding reliability, patient migration to an area that is not
covered by SEER and limited information on the treat-
ment details of the patients. These limitations make it dif-
ficult to interpret the time trend in treatment of thyroid
cancer and its influence on thyroid cancer related sur-
vival. Due to the excellent treatment outcome of most
thyroid cancers, randomized controlled trials to assess
treatment response will require prohibitively large sample
size and resources and therefore, they are not readily fea-
sible [20]. A population-based cohort with low attrition
rates such as ours (only 2.1% loss to follow-up over
40 years) is the probably the best possible model to study
the time trends in thyroid cancer survival. As all members
of the cohort received the same treatment, that was the
standard of care for their era, and their medical records
were individually reviewed for accuracy and completeness;
our study cohort was a reliable and stable model to study
the trends and factors influencing survival of patients
with thyroid cancer.
Our study shows that the incidence of thyroid cancer
in the province of Manitoba has increased by 373% from
1970 to 2010 that has resulted largely from an increase in
the number of papillary thyroid cancers (Table 1). The
proportion of cancers classified as follicular variant of
papillary thyroid cancer has almost tripled from 12.4% to
32.9%; this has also contributed to the increase in the
proportion of papillary thyroid cancer. At the same time,
the proportion of follicular thyroid cancer has decreased
from 26% to 5.1%, possibly due to a change in the crite-
ria for diagnosing papillary carcinoma after 1988,
whereby, all lesions with typical cytological features
(ground-glass nuclei, nuclear grooves, and psammoma
bodies) were classified as papillary carcinoma even if they
did not show papillae [21]. Thus, many erstwhile follicu-
lar thyroid cancers are rechristened as follicular variant of
papillary thyroid cancer. During the last four decades, the
10-year DSS has improved from 85.4% to 95.6%, whereas
the 10 year DFS has remained stable (86.6–91.9%).
In 2012, thyroid cancers (N=5650) were expected to
account for 2.1% of all cancers (N=267,700) in Canada
[1]. The number of the newly diagnosed thyroid cancer
in the province of Manitoba has increased by over three-
fold in the last four decades which is congruent with
Table 3. Multivariate analysis by Cox proportional hazard models for
independent influence of prognostic factors on disease-specific
survival.
Prognostic factor
Hazard ratio
(95% confidence interval)
Age at the time of diagnosis
(per year)
1.05 (1.03–1.06), P<0.001
Gender (male vs. female) 1.79 (1.28–2.51), P=0.001
Extent of thyroidectomy
(hemi vs. total)
0.991 (0.60–1.64), P=0.971 (NS)
Completeness of resection
(incomplete vs. complete)
2.40 (1.37–4.19), P=0.002
Adjuvant radioactive iodine
(RAI vs. no RAI)
1.59 (0.91–2.79), P=0.101(NS)
AJCC TNM stage grouping
Stage I 1.00 (reference)
Stage II 1.94 (0.78–4.84), P=0.155 (NS)
Stage III 2.30 (1.00–5.29), P=0.05
Stage IV 8.37 (3.99–17.54), P<0.001
Histology
Papillary 1.00 (reference)
Anaplastic 8.66 (5.18–14.49), P<0.001
Medullary 2.62 (1.48–4.66), P=0.001
H€
urthle 2.23 (1.21–4.14), P=0.010
Follicular 1.76 (1.01–3.09), P=0.047
Decade of diagnosis
1970–1980 1.00 (reference)
1981–1990 0.92 (0.56–1.53), P=0.753 (NS)
1991–2000 1.40 (0.91–2.17), P=0.126 (NS)
2001–2010 0.65 (0.40–1.08), P=0.096 (NS)
ª2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. 5
K. A. Pathak et al. The Changing Face of Thyroid Cancer
reports from Canada and other countries [2–13]. How-
ever, this increase in our study cohort has not been
restricted to the smaller thyroid cancers as has been
thought of earlier [2, 4, 7, 17]. We observed an increase
in the number of thyroid cancers of all sizes, which is a
true increase in the incidence of thyroid cancer in Mani-
toba and it cannot be explained only by over diagnosis of
subclinical disease. A single cause for this increase is not
apparent and this may be multifactorial due to iodine
deficiency [22], radiation exposure [23–25], long-standing
goiters, and family history [26]. The shift in histological
pattern of thyroid cancer has been reported from other
regions also [27]. The decrease in proportion of anaplas-
tic carcinoma could be a result of more aggressive treat-
ment of goiters and differentiated thyroid cancers by
thyroidectomies before they could undergo anaplastic
transformation. The proportion of tumors >2 cm in our
cohort is higher than that reported earlier [7, 16, 28],
because of the strict criteria for fine needle biopsy of thy-
roid in Manitoba. Most of the microcarcinomas in our
study were incidentally detected in thyroidectomy or
autopsy specimens. Even before the introduction of the
American Thyroid Association guidelines [29], which rec-
ommend threshold sizes of >1 cm (hypoechoic solid nod-
ule), 1–1.5 cm (iso or hyperechoic solid nodule), 1.5–
2 cm (mixed cystic–solid nodule with suspicious fea-
tures), and ≥2.0 cm (mixed cystic–solid nodule without
suspicious features) in a low-risk patient without cervical
lymphadenopathy or microcalcification, radiologist and
surgeons were very conservative in their approach. This is
also reflected by a large proportion of patients (44.9%)
having less than a total thyroidectomy.
During 1970–2010, the DSS for thyroid cancer has
improved by 10.2%, cumulative incidence of death due to
thyroid cancer fell by 8.1%, whereas the DFS for patients
treated with radical intent has remained unchanged
(Table 1). This improvement is not because of an increase
in the proportion of early-stage disease or smaller tumors
in recent years (Table 1). Although both total thyroidec-
tomy and adjuvant RAI treatment have been used more
often during the recent time (Table 1), they did not have
any significant impact on DSS (Table 3). To maintain
homogeneity of data across the study period, only clini-
cally and radiologically detectable disease relapses were
considered as recurrences. Isolated hyperthyroglobulin-
emia was not considered as an evidence of recurrence.
More aggressive treatment of early stage disease has not
resulted in a significantly better disease control, as
reflected by a stable disease free survival during this per-
iod. Therefore, the aggressive use of adjuvant RAI should
be judiciously balanced against the treatment-related
morbidities and the risk of developing second primary
cancer.
On multivariate analysis, DSS was negatively influenced
by nonpapillary tumor histology, male gender, advanced
tumor stage, incomplete surgical resection, and older
age at diagnosis (Table 3). Patient demographics,
completeness of surgery, and initial cancer stage have not
changed significantly in our study cohort (Table 1), how-
ever, there has been a marked change in the relative pro-
portion of various types of thyroid cancer diagnosed over
this time period. The proportion of papillary thyroid can-
cer has increased from 58% (1970–1980) to 85.9% (2000–
2010) and the proportion of anaplastic cancers fell from
5.7% (1970–1980) to 2.1% (2001–2010). As papillary thy-
roid cancer has the best survival rates (96.8% at 10 years)
and anaplastic thyroid cancer has the worst (7.3%
survival at 10 years), the opposite trends in the relative
incidence of papillary and anaplastic thyroid cancers is
most likely responsible for the improved outcome of thy-
roid cancer (Tables 1 and 2). After controlling for other
independent prognostic factors influencing DSS of thyroid
cancer in a multivariate model, there was no difference in
the DSS of thyroid cancer observed over the last four
decades (Table 3).
A time span of four decades is both strength as well as
a limitation of our study as the diagnostic criteria, stag-
ing, and treatment recommendations have evolved over
time. We tried to circumvent this challenge by uniformly
restaging all cancers using the 2009 AJCC/UICC Cancer
Staging System for thyroid cancer. Additionally, as a part
of our collaborative staging project, the pathology and
treatment details of 683 (29.6%) cases were independently
reviewed for accuracy and topography, and histology were
recoded by WHO International Classification of Diseases
for Oncology (3rd edition) codes. In view of prolonged
course of most thyroid cancers, it is possible that other
causes of mortality, unrelated to thyroid cancer, could
result in overestimation of thyroid cancer deaths by Kap-
lan–Meir method. Consequently, we used competing risk
regression to obtain unbiased estimation of cumulative
incidence of deaths resulting from thyroid cancer which
showed a significant change over the study period. A
competing risk is an event the occurrence of which either
precludes or changes the probability of occurrence of
another event of interest. In this study deaths to second
primary cancer and noncancer deaths were treated as
competing risks.
To conclude, we observed a true increase in the inci-
dence of thyroid cancer in the province of Manitoba that
cannot be attributed to over diagnosis of subclinical dis-
ease alone. A 10.2% improvement in DSS of thyroid can-
cer over the last four decades in our population cohort
was independent of early diagnosis or more aggressive
treatment. The major factor contributing to this improve-
ment in survival is the increasing proportion of papillary
6ª2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
The Changing Face of Thyroid Cancer K. A. Pathak et al.
thyroid carcinoma diagnoses and a corresponding
decrease in anaplastic thyroid carcinoma diagnoses, as
outcomes for the former are usually excellent whereas
outcomes for the latter are typically dismal.
Acknowledgments
This study was supported by the University of Manitoba
Research Grant and the Department of Surgery, Univer-
sity of Manitoba Research Grant. The authors acknowl-
edge the assistance provided by the staff of Departments
of Epidemiology and Cancer Registry, CancerCare Mani-
toba and of Medical Records, CancerCare Manitoba and
Health Sciences Centre.
Conflict of Interest
None declared.
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