Journal of Cancer Therapy, 2012, 3, 853-858
http://dx.doi.org/10.4236/jct.2012.325109 Published Online October 2012 (http://www.SciRP.org/journal/jct)
853
Long-Term Trends in the Survival of Women with
Endometrial Cancer in Canada: A Population-Based
Study*
Laurie Elit1,2#, Alice Lytwyn1,3, Noori Akhtar-Danesh1,4
1Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada; 2Department of Obstetrics and Gy-
necology, McMaster University, Hamilton, Canada; 3Department of Pathology and Molecular Medicine, McMaster University, Ham-
ilton, Canada; 4School of Nursing, McMaster University, Hamilton, Canada.
Received April 20th, 2012; revised May 23rd, 2012; accepted June 6th, 2012
ABSTRACT
Introduction: Annually in Canada, endometrial cancer affects approximately 4500 women and 790 are expected to die
of their disease. To better understand survival trends across the country we undertook this population based study of
Canadian women diagnosed with endometrial cancer. Long term trends in relative survival were evaluated by age and
geographic region of residence. Methods: Women with an ICD-10 code of C54 and endometrial cancer were identified
from the Canadian Cancer Registry. They were included if the incident diagnosis occurred between 1992 and 2005, and
they were 16 years and older at diagnosis. A flexible parametric model was used to determine relative survival ratio (i.e.,
the observed survival rate among cancer patients divided by the expected survival rate in the general population). Re-
sults: 18,486 women were diagnosed with endometrial cancer. Mean age was 63.4 (SD = 11.8) year. Relative survival
decreased with each successive age group cohort of patient (16 - 49 yr compared to over 60 years, p < 0.001). When
relative survival was adjusted for age, women in British Columbia had the best outcomes (eastern Canada compared to
other jurisdictions p < 0.001). Five-year survival outcomes improved for each age group cohort during the 1992 to 2005
time frame. Conclusions: Regional variations in relative survival were identified across Canada for women with endo-
metrial cancer. This suggests that other factors related to the patient or processes of care are involved. Examining these
factors in further detail may provide opportunities to improve the care of women with endometrial cancer in Canada.
Keywords: Endometrial Cancer; Relative Survival
1. Introduction
Uterine cancer is the most common gynaecological can-
cer. The Canadian Cancer Society reports that uterine
cancer affects about 4500 women across Canada annu-
ally, and about 790 women are expected to die from this
disease every year [1]. Trends in incidence and survival
over time and across jurisdictions can suggest where pat-
terns of care may offer benefit. Population studies pro-
vide an opportunity to measure outcomes variables such
as overall survival and disease free survival, while ad-
justing for variations in patient factors (i.e., age, weight)
[2]. Such information can be highly relevant to clinicians,
patients and health administrators. For instance, regional
variations may inform strategies for more optimal care
delivery patterns. Investigation of potential health care
delivery factors may help differentiate between those that
do or do not appear to impact on out-come. For example,
in 2007, Kwon et al. [3] showed that wait times for en-
dometrial cancer surgery in Ontario increased, but their data
did not show any impact on outcome.
Uterine cancer is made up of malignancies arising
from the epithelial cells (otherwise known as endometrial
cancer) or the stromal cells (i.e., leimyosarcoma, endo-
metrial stromal sarcoma, mixed mesodermal tumor to
name a few) or metastatic to the uterus (i.e., lymphoma).
Endometrial cancer is the most common subtype of uter-
ine cancer. In this paper we undertake to describe the
survival patterns for women diagnosed with endometrial
cancer in Canada over the period of 1992-2005. We ex-
amine whether long-term trends in relative survival are
dependent on patient age and geographic region of resi-
dence.
2. Patients and Methods
*Conflict of interest statement: the authors declare that there are no
conflicts of interest.
#Corresponding author. We identified women with endometrial cancers in the

Long-Term Trends in the Survival of Women with Endometrial Cancer in Canada: A Population-Based Study
854
Canadian Cancer Registry (CCR) dataset using the In-
ternational Statistical Classification of Diseases and Re-
lated Health Problems, Tenth Revision (ICD-10). First
we indentified tumours with codes C54.0 (Isthmus uteri-
including lower uterine segment), C54.1 (Endometrium),
C54.2 (Myometrium), C54.3 (Fundus uteri), C54.8 (Over-
lapping lesion of corpus uteri), and C54.9 (Corpus uteri,
unspecified). Then, using the International Classification
of Diseases for Oncology (ICD-O-2 or ICD-O-3) codes,
the analysis was limited to patients with only endometrial
adenocarcinoma [4]. Patients were excluded if the diag-
nosis was only based on the death certificate or autopsy.
Women were included if they had a new diagnosis of en-
dometrial cancer from 1992-2005 and were between 16
years or older at the time of diagnosis. Follow-up informa-
tion was retained until the end of 2006.
For the analysis by age, women were grouped into
strata given their age at diagnosis (16 - 49, 50 - 59, 60 -
69, 70 - 79, and 80 and over).
The geographical region was identified based on the
patient’s postal code at time of diagnosis. Given that
health care in Canada is provincially funded, women
were grouped based on the province at the time of diag-
nosis. In addition, because of small sample size some
provinces were collapsed into geographically cohesive
regions. The resulting geographic regions from west to
east were: 1) British Columbia; 2) central-west and
northern Canada: Alberta, Saskatchewan, Manitoba,
Yukon, Nunavut, Northwest Territories; 3) Ontario; and
4) eastern Canada: New Brunswick, Nova Scotia, Prince
Edward Island and Newfoundland. Data for the province
of Quebec were excluded because the data on deaths was
not available.
3. Statistical Analysis
It has become standard to use relative survival analysis
for population-based cancer registry datasets [5,6]. Rela-
tive survival ratio (or simply relative survival) is defined
as the observed survival rate among cancer patients di-
vided by the expected survival rate in the general popula-
tion of the same age and sex. It shows the extent to which
cancer shortens life [7,8]. The advantage of relative sur-
vival is that there is no need to know the actual cause of
death, although it includes all causes directly or in-
directly associated with the diagnosis of cancer [7]. It is
often age-adjusted to account for the fact that the risk of
death increases as we age and the population is aging
over time.
We used the flexible parametric model [9,10] to esti-
mate the relative survival ratio for different age groups
and regions. To estimate the relative survival, the back-
ground mortality rate for the general population (the rate
at which the death occurs in the general population) was
incorporated in the model. The background mortality rate
is usually derived from the country’s life-table. We re-
trieved an abridged 5-year background mortality rate
from the Statistics Canada website [11].
First, we fitted two separate models; one for each of
the independent variables of age group and the geo-
graphical region. Then, we incorporated age group, geo-
graphical region, and year of diagnosis into a final statis-
tical model using a stepwise forward approach to esti-
mate the relative survival where the effect of each vari-
able was adjusted for the effects of the other variables.
To include year of diagnosis in the model, a restricted
cubic splines with five knots was used. Restricted cubic
splines [12] adds more flexibility to the potential non-
linear relationship between relative survival and year of
diagnosis. The likelihood ratio test was used to compare
between different models. After fitting the final model
we predicted the two- and five-year relative survival ratio
for each age group and region based on the year of diag-
nosis [13].
The flexible parametric model was fitted using the
freely available stpm2 software developed by Lambert
and Royston [9] for the Stata package. Descriptive statis-
tical analysis was conducted using Stata/SE 12.0 (Stata
Corporation, College Station, TX).
4. Results
A total of 18,486 women were identified with endo-
metrial cancer between 1992 and 2005. Their mean age
at diagnosis was 63.4 (SD = 11.8) year (median 63 years).
Table 1 shows the age distribution at diagnosis and the
number of deaths among endometrial cancer patients for
each age group by geographic region. Only 11.1% of
women were pre-menopausal (using age less than 50 as a
proxy for premenopausal status) at time of diagnosis and
88.9% were 50 years old and over. Over half of all the
endometrial cancers were diagnosed in Ontario. This is
almost equal to the proportion of females in the general
population in Ontario compared to the rest of Canada
(excluding Quebec) [13]. The highest rate of death
(21.6%) was noted in Eastern Canada compared to On-
tario (20.3%), British Columbia (14.0%; the lowest rate),
and Central-West & Northern Canada (18.9%). In total
3591 patients (19.4%) diagnosed with endometrial cancer
died by the end of 2006.
Relative survival by age group is shown in Figure 1.
Relative survival clearly decreased with age. Women
under 50 years had a statistically superior relative sur-
vival compared to women 60 years and old (p < 0.001).
The relative survival ratios for the geographic regions
are presented in Figure 2. While the curves are relatively
close, relative survival is lower for Eastern Canada com-
pared to the other regions (p < 0.001). As can be seen,
British Columbia has the highest relative survival com-
pared to the other geographical regions. These differ-

Long-Term Trends in the Survival of Women with Endometrial Cancer in Canada: A Population-Based Study
855
Table 1. Distribution of age and death based on the province at the time of diagnosis for endometrial cancer patients.
Ontario British Columbia Eastern Canada Central-West & Northern
Canada Total
n (%) # of death n (%) # of deathn (%) # of deathn (%) # of death n (%) # of death
AGE GROUP
<50 year 1100 (10.4) 92 228 (11.4) 10 204 (12.5)23 515 (12.2)34 2047 (11.1) 159
50 - 59 year 2943 (27.7) 282 567 (28.3) 29 471 (28.9)42 1220 (28.8)103 5201 (28.1) 456
60 - 69 year 3168 (29.8) 557 617 (30.8) 76 436 (26.8)84 1215 28.7)204 5436 (29.4) 921
70 - 79 year 2450 (23.1) 753 391 (19.5) 85 361 (22.2)116 921 (21.8)256 4123 (22.3) 1210
≥80 year 957 (9.0) 474 201 (10.0) 80 157 (9.6)87 364 (8.6)204 1679 (9.1) 845
Total 10,618 2158 2004 280 1629 352 4235 801 18,486 3591
Figure 3. Trends in two-year relative survival based on age
group in patients diagnosed with endometrial cancer in
Canada during 1992-2005 with follow-up to 2006.
Figure 1. Relative survival based on age group at diagnosis.
Figure 2. Relative survival based on the geographical re-
gion. Figure 4. Trends in five-year relative survival based on age
group in patients diagnosed with endometrial cancer in
Canada during 1992-2005 with follow-up to 2006.
ences remain statistically significant even when adjusted
by age group.
The results from fitting a flexible parametric model
including age group, the geographical region, and year of
diagnosis are also presented as two- and five-year rela-
tive survival ratio based on year of diagnosis for different

Long-Term Trends in the Survival of Women with Endometrial Cancer in Canada: A Population-Based Study
856
age groups (Figures 3 and 4). These figures indicate that,
in general, two- and five-year survival for endometrial
cancer patients improved for all age groups over the pe-
riod of 1992-2005.
5. Discussion
To our knowledge, this is the first study using the flexi-
ble parametric model to estimate long-term relative sur-
vival for endometrial cancer in a population-based study.
Use of flexible parametric models in survival analysis is
quite new; although the theoretical paper was published
by Royston and Parmar in 2002 [10]; the actual “how to
do” paper was published in 2009 by Lambert and Roys-
ton [9]. We chose a flexible parametric model because it
is more flexible and more powerful compared to the
other methods in mimicking the actual trends in mortality
(hazard rate) and survival pattern in datasets.
In year 2000 the overall 5-year relative survival in the
Canadian population was well above 80% for all age
groups for the patients diagnosed with endometrial can-
cers (Figure 4) and the average 5-year relative survival
was 89.4%. This is in keeping with the age standardized
values quoted in the literature [14-17]. This is higher
than the Cancer System Quality Index (CSQI) Cancer
Care Ontario reported rate of 83% for 1994-1998 and
2004-2008. This later rate was for all histologic types of
cancer involving the uterus.
As Lee et al. [18] pointed out, endometrial cancer is
primarily known as a postmenopausal disease and it is
uncommon to find endometrial cancer in women during
their reproductive years. In Lee’s work, less than 15% of
endometrial cancer patients were premenopausal [18]. In
our study 11.1% of women with endometrial cancer were
premenopausal which included over 2000 women less
than 50 years of age. Other studies that focused on en-
dometrial cancer in the reproductive aged women have
small numbers of women. Our analysis corroborates a
survival benefit for the reproductive age group compared
to older aged women.
We found that relative survival is highly dependent on
the age of diagnosis. We showed that relative survival
decreases with increasing age and this has also been seen
in the USA [19,20] and the Nordic Countries [16]. This
may in part be related to higher rate of co-morbidities in
older women, earlier diagnosis of endometrial cancer in
younger women because of indicators such as changes in
menstrual function or increased self awareness (i.e., body
image), as well as more aggressive histological types in
older women.
Over the period of 1992-2006 there has been a general
drift toward improving survival time over all age groups.
Our analysis indicates that two- and five-year survivals
have risen slightly over this time frame. Similar trends
have been reported in the USA [19], Japan [21], UK [22]
and the Nordic countries [16]. In part this may reflect
shorter wait times and better diagnostic techniques to
identify endometrial cancer and thus down staging, im-
proved anaesthesiology and postoperative care, improved
therapies for uterine cancer, access to several lines of
adjuvant chemotherapy and biologic agents, and access
to palliative care (i.e. , less postoperative mortality after a
palliative bowel resection).
This is the first report that compares relative survival
ratio for endometrial cancer among geographic regions of
Canada which identified a higher relative survival ratio
in British Columbia compared to the other regions (Fig-
ure 2). This difference remained the same after adjusting
for age group. This may reflect variations in patient factors
(i.e., body mass index, ethnicity) or process issues (i.e.,
access to diagnostic tests, access to surgery, opportunity
for subsequent lines of chemotherapy or biologic agents).
The strengths of this work include the high quality
data as it is nationwide and population-based. In addition,
we analyzed information from a large population (more
than 18,000 women over fifteen years (1992-2006)).
A notable limitation of this paper is that we were un-
able to adjust the analysis based on the stage or grade of
tumours as this information is not currently available
from CCR dataset. Access to other patient information
like race [19,20] size of dwelling and marital status [15],
status of disease details like stage and grade [20,23,24],
histology [24], treatment information like details of the
surgical intervention [23,24], subsequent treatment [23-
25], could help focus in on the potential reason(s) for
variations in outcome that are identified. Another limita-
tion is that we used the general survival for the Canadian
population as our standard for survival. Survival may
vary by geographic region and thus general survival for
region may have been a superior method. Unfortunately,
this information is not available. Another limitation is
that the model combines cancer related death rather than
cause specific death i.e., death from cancer versus death
from treatment complication. This finer level of informa-
tion was not available to us. Another limitation is that
administrative databases were never designed for popula-
tion based studies. Thus any results are hypothesis gen-
erating and require further investigation by other meth-
ods to validate the hypothesis.
6. Conclusion
This work indicates that in Canada, when relative sur-
vival is used to measure outcome, both patient age at
diagnosis and geographic region of residence affect out-
come. When adjusted for age at diagnosis, geographic
region of patient residence affects continues to influence.
Evaluating other factors either related to disease (i.e.,
histological type), patient (i.e., body mass index) or proc-

Long-Term Trends in the Survival of Women with Endometrial Cancer in Canada: A Population-Based Study 857
esses of care (i.e., wait times for surgery) may act as
confounders in the variations in relative survival seen by
region. If differences in relative survival by region persist
despite controlling for such confounders, this may sug-
gest opportunities to improve care.
7. Acknowledgements
The authors wish to thank the Canadian Cancer Registry
and Statistics Canada for allowing us access to the data-
set. We also wish to thank the staff of the Research Data
Centre, McMaster University for their help.
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