Clinical epidemiology of epithelial ovarian cancer in the UK

Abstract

Epithelial ovarian cancer is the fifth commonest cancer among women and the leading cause of gynecological cancer death in the UK. Most women present with advanced disease, mainly because the nonspecific nature of the symptoms lead to diagnostic delays. Recent data have shown a fall in ovarian cancer mortality rates in the UK, but rates are still higher when compared to other European countries or the USA. In addition, surgeons in the UK achieve on average lower optimal surgical cytoreduction rates in patients with advanced ovarian cancer. Despite a wealth of information on epidemiological risk factors, the pathogenesis of epithelial ovarian cancer remains largely unknown. This review presents the most recent data on incidence, mortality, and survival for epithelial ovarian cancer in the UK. Time trends, trends by age, international comparisons, and regional variation in incidence, survival, and mortality are presented within the context of a major reorganization of cancer services that took place in the UK over 10 years ago. Centralization of cancer services has meant that women with ovarian cancer receive treatment in specialist Cancer Centers.

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http://dx.doi.org/10.2147/IJWH.S40894
Clinical epidemiology of epithelial ovarian
cancer in the UK
Konstantinos Doufekas
Adeola Olaitan
Department of Gynaecological
Oncology, University College
London Hospitals, London, UK
Correspondence: Adeola Olaitan
Department of Gynaecological Oncology,
University College London Hospitals,
2nd Floor East, 250 Euston Road,
London, UK, NW1 2PB
Tel +44 203 447 8636
Fax +44 3447 9883
Email adeola.olaitan@uclh.nhs.uk
Abstract: Epithelial ovarian cancer is the fifth commonest cancer among women and the leading
cause of gynecological cancer death in the UK. Most women present with advanced disease,
mainly because the nonspecific nature of the symptoms lead to diagnostic delays. Recent data
have shown a fall in ovarian cancer mortality rates in the UK, but rates are still higher when
compared to other European countries or the USA. In addition, surgeons in the UK achieve on
average lower optimal surgical cytoreduction rates in patients with advanced ovarian cancer.
Despite a wealth of information on epidemiological risk factors, the pathogenesis of epithelial
ovarian cancer remains largely unknown. This review presents the most recent data on inci-
dence, mortality, and survival for epithelial ovarian cancer in the UK. Time trends, trends by
age, international comparisons, and regional variation in incidence, survival, and mortality are
presented within the context of a major reorganization of cancer services that took place in the
UK over 10 years ago. Centralization of cancer services has meant that women with ovarian
cancer receive treatment in specialist Cancer Centers.
Keywords: ovarian, cancer, epidemiology, UK, incidence, survival
Introduction
Epithelial ovarian cancer (EOC) is the fifth most common cancer among women and
the leading cause of death from gynecological cancer in the UK.1,2 Each year more than
6,500 women are diagnosed with ovarian cancer in the UK and about 4,400 women
die of the disease.3,4
Over the past 20 years the incidence of ovarian cancer in England has remained
fairly static, but mortality rates have fallen by over 20% since 2000.5 However, the
outlook for women with ovarian cancer remains poor, with an overall 5-year survival
rate below 45%.3
Large epidemiological studies have reported substantial differences in ovarian
cancer survival in the UK when compared to other European countries, Australia, and
Canada.1,6,7 This is in spite of the UK having a lead role in both research and training,
conducting many of the major trials in ovarian cancer research, and being the first
European country to implement formal gynecological oncology training.
The aim of this review is to present an overview of clinical epidemiology for EOC
in the UK, with an emphasis on incidence, mortality, and survival trends.
Late presentation and lack of effective screening impede early detection of ovar-
ian cancer. There are often delays between onset of symptoms and diagnosis and as a
result, most women present with advanced stage disease, when cure rates are low. The
current standard of care is cytoreductive surgery and platinum-based chemotherapy.
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Doufekas and Olaitan
Most ovarian cancers originate from the surface epithelium
of the ovary. The majority of EOCs are sporadic, although a
small percentage are familial and have a genetic etiology. The
sporadic group of EOC presents a major challenge in defining
the etiology of the disease. The role of some factors, such as
parity, is well defined, while the role of others, such as the use
of ovulation-inducing drugs, remains controversial.8
The National Health System in the UK is one of the
largest health care systems in the world.9 In a white paper,10
(Equity and excellence: Liberating the NHS, 2010), the UK
government proclaimed a strategy to achieve outcomes in
cancer that are among the best in the world.9
Overview of the UK National
Health System
The UK National Health Service (NHS) is the world’s larg-
est publicly funded health service.11 The clinical sector is
divided into primary, secondary, and tertiary care. Primary
care is provided by general practitioners (GPs). Secondary
or hospital-based care is accessed through GP referral, and
tertiary care includes specialist hospitals.
The 1995 Calman–Hine report prompted a massive
reorganization of the UK’s cancer services.12 The report pro-
posed a strategy to improve outcomes and reduce inequali-
ties in NHS cancer care. The 1999 Improving Outcomes
Guidance13 and subsequent NHS Cancer Plan14 provided
further specifications of this new strategy. Cancer Networks
were established with an emphasis on multidisciplinary
team cancer specialist care.15 These networks incorporate
a number of cancer units responsible for rapid diagnosis
which then refer high risk patients to a cancer center for
further management by trained gynecological oncologists.
A sufficient concentration of work can thus be achieved in
cancer centers to maintain expertise.16 There are currently
41 cancer centers within Cancer Networks in England.
Centralization of care for women with ovarian cancer has
been the subject of debate,17,18 but evidence from a recent
meta-analysis19 indicates that centralization of care for
gynecological cancer improves overall survival.
Until March 2013, ten strategic health authorities (SHAs)
managed the NHS at the regional level and primary care trusts
commissioned primary, community, and secondary health ser-
vices from providers. New organizations such as clinical com-
missioning groups are now replacing the old NHS structure.11
Data collection
The United Kingdom has one of the most comprehensive
cancer registration systems in the world.20 Eleven cancer
registries covering England, Wales, Scotland, and North-
ern Ireland collate the data on incidence, mortality, and
survival of ovarian cancer.20,21 Data are then analyzed and
published by the Office of National Statistics (ONS). There
is a 2-year lag between event recording and the publication
of summary statistics by cancer registries and the ONS.21
Data completeness is high for diagnosis and deaths, but
more variable information is recorded on management and
treatment.21 The National Cancer Intelligence Network
(NCIN) uses information collected by cancer registries
for analysis, publication, and research. The Trent Cancer
registry is NCIN’s lead registry in England for gynecologi-
cal cancers.
International comparisons can be made with global
and European data from GLOBOCAN and EUROCARE
projects and the International Cancer Benchmarking
Partnership (ICBP).
Denition
In the latest NCIN report “Ovarian Cancer: Incidence,
Mortality and Survival,” ovarian cancer is defined according
to the second edition of the International Classification of
Diseases for Oncology (ICD-0-2).5 The ICD-0-2 classifica-
tion includes “borderline tumors” within the category of
“malignant ovarian neoplasms.”
The ICD-0-2 was introduced in England and Wales in
1995, followed by Northern Ireland in 1996 and Scotland
in 1997. The newer third edition of the International Clas-
sification of Diseases for Oncology (ICD-0-3) has removed
borderline tumors from malignant ovarian neoplasms.
The ICD-0-3 classification has been used in the ICBP and
EUROCARE reports.6,7 Consequently, the survival estimates
in ICBP and EUROCARE appear lower than the survival
estimates of the NCIN report.5
Morphology
Fifty to sixty percent of ovarian neoplasms are epithelial in
origin and the most common histological subtype in the UK
is serous carcinoma.22 Serous subtype accounted for one-third
of all cases in 2009, being commonest in women aged 45
and over.5 Unclassified EOC was the second commonest type
and was commonest in women older than 75. Women with
unclassified EOC have the worse mortality.
Over the past 10 years, there has been a 30% decrease in
the number of unclassified cases and a 38% increase in the
number of serous ovarian cancers.5 The relative frequency
of other subtypes has remained fairly stable. The decrease in
the number of unclassified epithelial cases may have resulted

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539
Clinical epidemiology of epithelial ovarian cancer in the UK
from better coding and recording of ovarian cancer morphol-
ogy by cancer registries.5
Stage
In the UK, cancer registries use the TNM classification
to stage cancer, similar to the International Federation
of Gynecology and Obstetrics staging. TNM staging is
derived on the basis of information obtained from surgery,
imaging, and histopathology. Currently, data on ovarian
cancer stage at presentation are only available from the
Welsh Cancer Intelligence and Surveillance Unit21 and the
East Anglia Registry.
Most women in the UK are diagnosed with advanced
stage disease. Sixty percent present in stages III and IV and
only around 30% are diagnosed in the early stages I and II.
Over the past 20 years there has been a clear improvement in
5-year survival for patients with stage I disease, an increase
from 80% to 92%. In stage II disease, 5-year survival
increased from 30% to 55%, but the confidence intervals
are wide, thus making conclusions less certain.3 A small
but consistent increase in 5-year survival has been seen in
stage III disease, but the national average figure remains
low at 22%.3 Survival in patients with stage IV disease has
remained static and only 5.6% are still alive at 5 years.3 The
International Federation of Gynecology and Obstetrics Com-
mittee on Gynecologic Oncology has recently published a
revised staging classification for cancer of the ovary, fallopian
tube, and peritoneum.23
Etiology
The pathogenesis of ovarian cancer remains controversial
even though epidemiological studies have gleaned an enor-
mous amount of information.8 Most studies have focused
on the epidemiology of invasive EOC.24 The role of some
factors, such as parity, is well established whereas the role
of others such as infertility and its treatment remains more
controversial. The evidence base for these associations has
been elegantly discussed in previous reviews.8 A brief sum-
mary of some salient risk factors is presented below.
Age
Data from the US Surveillance, Epidemiology, and End
Results database have clearly demonstrated that age bears
a strong relation to ovarian cancer risk.8 The incidence is
low in women under the age of 40, but rises steeply after
the fifth decade to reach a peak in the 80- to 84-year old age
group (incidence of 61.8 per 100,000 women).8 The median
age at diagnosis is currently 63 years.1,2,25,26 With an aging
population in the UK and other Western countries, the total
number of ovarian cancer cases can be expected to rise.
Family history
Genetic susceptibility is an important risk factor for ovarian
cancer, and approximately 10% of ovarian cancer cases are
caused by mutations that cluster in families.27 Mutations in
the BRCA1 and BRCA2 genes are responsible for approxi-
mately 90% of inherited predispositions to ovarian cancer.28,29
Mutations at the hereditary nonpolyposis colorectal cancer
gene and other loci account for the remaining. The lifetime
risk of ovarian cancer in BRCA mutation carriers ranges from
15%–60%.28,30 Screening for ovarian cancer in women who
carry BRCA mutations has been the focus of UK familial
ovarian cancer screening study trial.31
Reproductive factors
Parity and breastfeeding
The effect of increasing parity in reducing the risk is now
well established.8,32,33 Studies have shown a reduction in risk
reduction even with incomplete pregnancies.34 Breastfeeding
also seems to have a small protective effect.34
Menstrual life
Two large studies have failed to show a significant effect of
either early menarche or late menopause on ovarian cancer
risk.34,35 Length of menstrual cycle is therefore unlikely to be
a significant factor in the pathogenesis of ovarian cancer.
Infertility and its treatment
The role of infertility and infertility therapy remains less
clear. Studies have shown a trend towards an increased risk
of ovarian malignancies in infertile women.8 The risk seems
to be highest in a subset of women with unexplained infer-
tility.8,36 Currently, there is no proven association between
ovarian cancer and infertility treatment.37,38
Exogenous hormones
The combined contraceptive pill
Oral contraceptive use confers long-term protection against
ovarian cancer.8,32,39–42 The longer the use, the greater the
reduction in risk and the longer it persists.41 The use of oral
contraceptives is associated with a reduced risk of ovarian
cancer in women carrying a BRCA mutation.43
Hormone replacement therapy
Hormone replacement therapy use increases the risk of ovar-
ian cancer, but several small studies and a meta-analysis have

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Doufekas and Olaitan
shown only a small increase in risk, especially with more than
10 years of use.44,45 Short-term use is unlikely to increase the
risk of ovarian cancer.
Medical conditions
Endometriosis
Women with endometriosis have an increased risk of devel-
oping ovarian cancer.46,47 There is an association especially
with endometrioid and clear cell morphology.48 Unilat-
eral oophorectomy, as well as radical resection of visible
endometriosis, reduces the risk of later developing ovarian
cancer.49
Previous cancer
Studies have shown a twofold increase in the risk of ovarian
cancer in women with a history of breast cancer.50,51 The risk
may increase fourfold if their breast cancer is diagnosed
before the age of 40, and manyfold if they also have a family
history of breast or ovarian cancer.50 Radiotherapy treatment
for cervical cancer also carries a long-term risk of cancer in
the ovaries.52
Other factors
The sociodemographic behavior of women has undergone
important changes over the past 40 years that may influence the
incidence of ovarian cancer. Women’s ever increasing partici-
pation in the workforce often delays childbearing until later in
reproductive life. The mean age of women at childbirth in the
UK has continued to rise. It was 29.5 years in 2010 compared
with 28.5 years in 1995 and 27.2 years in 1962.53 Oral contra-
ceptive use has become more widespread and may be expected
to also have an influence on the incidence of ovarian cancer.54
Epidemiology
Detailed summary statistics on ovarian cancer in England
and UK can be found in recent publications by NCIN and the
National Institute for Health and Care Excellence (NICE).5,21
NCIN’s latest report, “Overview of Ovarian Cancer in England:
Incidence, Mortality and Survival,” was released in 2012,
and provides a detailed analysis of ovarian cancer statistics in
England up to 2009.5 NICE released national (UK) epidemiol-
ogy data in 2011, as part of a Clinical Guideline on the recogni-
tion and management of ovarian cancer.21 Cancer Research UK,
have also produced descriptive statistics on ovarian cancer.3
Incidence
Ovarian cancer incidence rates vary considerably worldwide
and across Europe. The highest rates have been recorded in
Central America and Northern, Central, and Eastern Europe.
The UK has ranked sixth among the 27 countries in the
European Union.55 In 2010 7,011 new cases of ovarian cancer
were diagnosed in the UK.3
Variation with age
Ovarian cancer is predominantly a disease of older women
and its incidence rises steeply after the usual age of
menopause. Over 80% of new diagnoses are in women over
the age of 50.5
Incidence reaches a peak in women over the age of 75.
This is true for all morphological types of ovarian cancer. In
2009, almost half of new ovarian cancer diagnoses were in
women over the age of 60 years (2,817 out of 5,849).5
Trends in ovarian cancer incidence
The age-standardized incidence rate (ASIR) of ovarian can-
cer in the UK has increased from 14.7 per 100,000 female
population in 1975 to 16.4 per 100,000 in 2007.21 Incidence
rates peaked between 1995 and 1999, which may have been
due to the introduction of the ICD-O-2 classification in the
UK.21 The ICD-O-2 was introduced in England and Wales
in 1995 and by 1997 it was also in use in Scotland and
Northern Ireland.
Ovarian cancer in England has been the focus of NCIN’s
recently published report.5 In England, over the past two
decades, the incidence of ovarian cancer has remained
fairly static. It has shown minor fluctuations, and there has
been a clear downward trend over the past few years. From
1989 to 1994, the ASIR of ovarian cancer ranged between
17 and 18 per 100,000. The rate rose to around 19 per
100,000 between 1995 and 2003, only to return to 17 to 18
per 100,000 after 2004, similar to rates in the early 1990s.
In 2009, in England there were just fewer than 5,900 new
diagnoses.
Over a period from 1989 to 2009, incidence rates in
England showed varying trends in different age groups. In
women aged 49 or less, incidence rates have remained fairly
static at around 9 per 100,000. In women aged 50–69, inci-
dence decreased from 48 to 40 per 100,000. In those over 70,
it increased from 57 to 70 per 100,000 between 1989 and
1999, but has decreased after 2000.
The decrease in incidence among women aged 50 and over
may reflect the protective effect of the combined contraceptive
pill that has been in widespread use since the 1960s. Women
who are currently over the age of 70 belong to the first cohort
of women that gained access to the oral contraceptive pill,
after it became widely available in the 1960s.

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Clinical epidemiology of epithelial ovarian cancer in the UK
Regional variation in incidence
The incidence of ovarian cancer shows some variation across
the constituent countries of the UK. Data from 200856 indi-
cate that Wales has the highest incidence rates followed by
Scotland, Northern Ireland, and England.
Data from SHAs and Cancer Networks within England
also indicate regional variation.5 Data from England over
2007 to 2009 show that the ASIR was lowest for women living
in the Southeast coast and London SHAs and highest in East
Midlands, Southwest, and South Central SHAs. Variation in
incidence rates within Cancer Networks broadly reflects the
trend seen across SHAs. Incidence rates appear highest in
the Peninsula and lowest in the Southeast London Cancer
Networks with ASIRs of 20.2 and 13.7 per 100,000 women,
respectively. The average ASIR in England from 2007 to
2009 was 17.5 per 100,000 female population.
There is no evidence to suggest a correlation between
deprivation and ovarian cancer incidence among various
primary care trusts in England.5
Mortality
Ovarian cancer is the leading cause of death in gynecologi-
cal cancer in both the United Kingdom and worldwide. In
2008, around 4,400 women died from ovarian cancer in
the UK. Data from EUROCARE suggest that the UK has
higher mortality rates when compared to the other European
countries.1,6
Fifteen percent of women diagnosed with ovarian cancer
in the UK in 2006–2008 died within 2 months, while one-
third died within the first year.5,21
Death within the first year is a reflection of presentation
with advanced disease.
Trends in ovarian cancer
mortality over time
The mortality rate for ovarian cancer in the UK has fallen
by 20% over the past decade.5 Age-standardized mortality
rates were stable between 1989 and 2002, ranging from
11 to 12 per 100,000, but had fallen to 8.8 per 100,000
by 2010.5 The reduction in mortality over the past decade
coincided with the reconfiguration of cancer services and
may reflect enhanced cancer care with better detection
and management within the UK specialist gynecological
cancer centers.
Mortality has shown varying trends across different age
groups. National data from 1971 to 2008 show that in women
over 65 years of age there has been a gradual increase in
mortality.21 In women aged 50 to 64 years there has been
steady decline and in those under 49 years the mortality rate
has been fairly constant.21
Geographical variation
The age-standardized mortality rates are similar across the
constituent countries in the UK. The highest mortality rate
is seen in Northern Ireland and the lowest in Wales. Within
England, mortality rates are highest in West Midlands and
South Central SHAs and lowest in London and Yorkshire
and the Humber SHAs.5 A similar variation is noted within
constituent Cancer Networks. Peninsula and Mid Trent
Cancer Networks had the highest mortality and North
London, West London, and Northeast London Cancer
Networks the lowest.21
There is no evidence that deprivation is related to ovarian
cancer mortality.5
Survival
Ovarian cancer survival rates remain the lowest among gyne-
cological cancers, both in the UK and worldwide.5,21 Women
often present late, with advanced staged disease and this has
a major negative impact on survival.
Variation with age
Survival is strongly related to age and younger women have
a better prognosis.
Data from the UK Cancer Information Service (UKCIS)
provide strong evidence of a worse survival from ovarian
cancer in older women. In England for example, over a
period from 2003 to 2009 women aged 15–39 achieved
1-year survival of 95.6% compared to a mere 24% in women
aged over 85.5 Five-year survival showed a similar dramatic
variation with age. In England over the same time period, the
5-year survival in the 15–39 age group was 84.2% compared
with 13.7% in those aged over 85.5
These differences in relative survival partly reflect differ-
ences in tumor biology, as well as the higher proportion of
borderline tumors in women of younger age. Other factors
may, however, also contribute to the gap in survival between
older and younger patients. Evidence from the General
Practice Research Database suggests that GPs may be less
likely to both diagnose and to refer women for gynecologi-
cal investigation as they get older.3,57 There are also often
difficulties in treating older women with both surgery and
chemotherapy, related to medical comorbidities or a low
performance status.
In addition, data from the NCIN show that over the past
20 years, both 1-year and 5-year survival in women over 80

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Doufekas and Olaitan
has failed to improve, despite the notable improvement in
all other age groups.5
Trends in survival
In the UK, both 1-year and 5-year survival have improved
since the mid-1980s, similar to other European countries.6,7
In England for example, from 1985 to 2009 1-year survival
increased from 57% to 73% and 5-year survival from 33%
to 43%.
Since 1987, the greatest improvement in 1-year
survival was seen in women aged 55–79, whereas the
greatest improvement in 5-year survival was seen in the
40–49 age group.5
These significant improvements may reflect the effect
of the new government strategies in gynecological cancer
through the establishment of Cancer Networks, specialist
centers, and oncology multidisciplinary teams. Surgery for
ovarian cancer is now centralized and provided by subspecial-
ist gynecological oncologists. Chemotherapy regimens have
also improved and combined taxane-platinum chemotherapy
is now the standard treatment.5 There is evidence that women
who receive treatment for ovarian cancer in specialized cen-
ters have longer survival than those managed elsewhere.19
Geographical variation
The latest NCIN data for England from 2003–2009 provide
evidence of cancer survival inequalities, with marked geo-
graphical variation for both 1-year and 5-year survival in
ovarian cancer. One-year survival is highest in Southwest
London, Pan Birmingham, and Yorkshire Cancer Networks.
The Pan Birmingham Cancer Network also shows the highest
5-year survival rate, along with North of England. In contrast,
Sussex Cancer Network demonstrates geographical clustering
of poor survival, with both 1-year and 5-year rates well below
the national average.5 These regional disparities in ovarian
cancer survival may be due to several factors, including dif-
ferential delays in referral and diagnosis and differences in
treatment or comorbidities among patients. Variable quality
of data capture across Cancer Networks may also be behind
regional inequalities.58
International variation
Despite the improvement in survival that has occurred in
recent years, data from EUROCARE and the ICBP show that
survival rates in the UK are still lower than in other European
countries, Australia, and Canada.1,6,7,59 This is in spite of the
UK having a similar health care system and similar percent-
age of women diagnosed at different stages of the disease to
other developed countries. Differences in coding and quality
of data collection between countries may account for some
of the noted differences.
Survival rates in the UK are highest in Northern Ireland,
followed by Wales, Scotland, and England.7,59 In Europe, the
highest survival rates are found in Scandinavia, Switzerland,
and Austria.59
Delays in accessing treatment through primary care or
differences in the quality of care could account for the lower
survival rate in the UK.60 A large percentage of patients
diagnosed with ovarian cancer in the UK continue to present
as an emergency. In 2007, for example, almost one-third of
such patients presented as an emergency.5
Differences in other factors, including public awareness
of cancer, comorbidity, and access to optimal treatment, may
also explain the survival deficit in the UK.7
Routes of diagnosis
The NCIN has recently published data on the different pathways
patients follow to reach a diagnosis of ovarian cancer.21 These
include routine and urgent GP referrals for symptoms of malig-
nancy, and other elective outpatient, inpatient, and emergency
presentations. The data refer to English patients diagnosed with
ovarian cancer between 2006 and 2008. They highlight a wide
variation in the way patients enter the diagnostic pathway. The
majority of ovarian cancer patients (64%) attend electively,
but one-third (30%) still presents as an emergency. Urgent GP
referrals account for almost one-quarter of all presentations. As
emergency presentation is associated with increased mortality,61
it remains a major challenge in the UK to reduce the proportion
of patients who present via the emergency route.
Treatment
Ovarian cancer treatment usually consists of surgery
and/or combination chemotherapy, depending on stage at
presentation.
Staging for ovarian cancer is surgico-pathological.
In women with suspected early (stage I) ovarian cancer,
complete surgical staging includes total abdominal hys-
terectomy, bilateral salpingo-oophorectomy, omentectomy,
random peritoneal biopsies, and block dissection of the
ipsilateral pelvic and paraaortic nodes. The NICE guidelines
do not advocate systematic lymphadenectomy as part of
standard surgical treatment,21 and this may lead to routine
under-staging.62,63 This guidance is not accepted by the British
Gynaecological Cancer Society.64
In advanced disease, the European Organisation for
Research and Treatment of Cancer 55971 and Medical

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Clinical epidemiology of epithelial ovarian cancer in the UK
Research Council CHORUS trial have assessed the impact
of the timing of surgery and chemotherapy.65,66 They both
indicate that delayed primary surgery does not have a
negative impact on survival and may reduce perioperative
morbidity.65,66
There is lack of national comparative data on treatment
modalities in the UK. Cancer centers have been slow to
develop comprehensive databases and publish their outcome
data.67
Data on surgical treatments in ovarian cancer have been
published for Wales by the Welsh Cancer Intelligence and
Surveillance Unit.21 The most frequent procedure undertaken
in the three Welsh Cancer Networks is total abdominal hyster-
ectomy, bilateral salpingo-oophorectomy, and omentectomy
as part of a staging laparotomy. Data from England are yet
to be published.
When compared to the USA and Europe, the UK achieves
on average low optimal surgical cytoreduction rates in
advanced ovarian cancer.65,66 Possible reasons for this discrep-
ancy have been explored previously and may include operat-
ing time constraints within NHS hospitals.67,68 The Medical
Research Council CHORUS trial reported zero residual
disease in 15% of primary and 35% of interval debulking
surgery, with an average duration of surgery of 2 hours.66
In the North London Cancer Network, University Col-
lege London Hospital currently achieves (based on internal
audit results) optimal cytoreduction rates of around 70%
for upfront surgery in advanced ovarian cancer. This is
comparable to data reported by other major centers, such as
the Mayo clinic.69
Data on chemotherapy use from two Cancer Networks
have revealed a marked variation between hospitals in the
percentage of patients receiving chemotherapy. Up to 40% of
older patients were managed with chemotherapy alone.21
There is however, evidence that more ovarian cancer
patients receive specialist treatment in England, as per the
Improving Outcomes Guidance. From 2000 to 2007 the
percentage of women with ovarian cancer operated on by
specialists increased from 17% to 48% and the percentage
treated in specialist centers increased from 40% to 71%.70
Currently, ovarian cancer patients in the UK receive
intraperitoneal chemotherapy only as part of the PETROC/
OV21 trial.
Conclusion
Ovarian cancer incidence in the UK has remained fairly
stable over at least two decades, although in recent years
there have been slight decreases in incidence. Mortality
rates have fallen by 20% since 2002.5 One-year and 5-year
survival following a diagnosis of ovarian cancer have both
improved significantly over the past two decades, although
there has been little or no improvement in survival rates of
the oldest women. Despite this, ovarian cancer remains the
leading cause of gynecological cancer death.
These trends have coincided with the centralization of UK
cancer services, which followed the Improved Outcomes Guid-
ance by the Department of Health over a decade ago. Women
with ovarian cancer in the UK receive treatment by specialist
gynecologic oncologists in tertiary referral centers.
However, regional variations in ovarian cancer mortality
and survival in the UK still exist, and it remains a challenge
to synchronize underperforming Cancer Networks with
national average scores.
In addition, survival remains lowest in all three UK nations
when compared to many other European countries.6 The wide
differences in survival may be explained by diagnostic delays
and variation in accessing optimal treatment in the UK.7 Cor-
recting the UK survival deficit should be a focus for policy mak-
ers in the UK and will remain a key indicator of progress.
Surgical centers in the UK need to develop and maintain
comprehensive databases which could yield a wealth of data
on outcomes such as morbidity, mortality, and survival. It also
remains a challenge to increase optimal cytoreduction rates
nationally and to avoid diagnostic delays within primary care, as
both of these factors can have a negative impact on survival.
Although epidemiological studies have provided a
wealth of information on the role of various risk factors,
there is still little consensus regarding the origins and
pathogenesis of EOC.
Disclosure
The authors report no conflicts of interest in this work.
References
1. Berrino F, De Angelis R, Sant M, et al; EUROCARE Working group.
Survival for eight major cancers and all cancers combined for European
adults diagnosed in 1995–1999: results of the EUROCARE-4 study.
Lancet Oncol. 2007;8(9):773–783.
2. Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002. Cancer Inci-
dence, Mortality and Prevalence Worldwide. IARC Cancer Base No 5,
Version 2.0. Lyon: IARC Press; 2004.
3. Ovarian cancer statistics [webpage on the Internet]. Oxford: Cancer
Research UK; 2013 [updated Jan 2013]. Available from: http://www.
cancerresearchuk.org/cancer-info/cancerstats/types/ovary/. Accessed
January 10, 2014.
4. Targeted Therapies for the Management of Ovarian Cancer (Scientific
Impact Paper No 12) [webpage on the Internet]. London: Royal College of
Obstetricians and Gynaecologists; 2013. Available from: http://www.rcog.
org.uk/womens-health/clinical-guidance/targeted-therapies-managment-
ovarian-cancer. Accessed January 10, 2014.

International Journal of Women’s Health 2014:6
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
544
Doufekas and Olaitan
5. Overview of Ovarian Cancer in England: Incidence, Mortality and
Survival (Nov 2012) [webpage on the Internet]. London: National
Cancer Intelligence Network. Available from: http://www.ncin.org.uk/
cancer_type_and_topic_specific_work/cancer_type_specific_work/
gynaecological_cancer/gynaecological_cancer_hub/resources/
ovarian_cancer. Accessed January 10, 2014.
6. De Angelis R, Sant M, Coleman MP, et al; EUROCARE-5 Working
Group. Cancer survival in Europe 1999–2007 by country and age:
results of EUROCARE-5-a population-based study. Lancet Oncol.
2014;15(1):23–34.
7. Coleman MP, Forman D, Bryant H, et al; ICBP Module 1 Working
Group. Cancer survival in Australia, Canada, Denmark, Norway,
Sweden, and the UK, 1995–2007 (the International Cancer
Benchmarking Partnership): an analysis of population-based cancer
registry data. Lancet. 2011;377(9760):127–138.
8. Edmondson RJ, Monaghan JM. The epidemiology of ovarian cancer.
Int J Gynecol Cancer. 2001;11(6):423–429.
9. Grosios K, Gahan PB, Burbidge J. Overview of health care in the UK.
EPMA J. 2010;1(4):529–534.
10. Equity and Excellence: Liberating the NHS. Department of Health
publications; 2010. Available from: https://www.gov.uk/government/
uploads/system/uploads/attachment_data/file/213823/dh_117794.pdf.
Accessed January 10, 2014.
11. The NHS in England [webpage on the Internet]. London: National
Health Service; 2013. Available from: http://www.nhs.uk/NHSEngland/
thenhs/about/Pages/overview.aspx. Accessed January 10, 2014.
12. Morris E, Haward RA, Gilthorpe MS, Craigs C, Forman D. The impact of the
Calman-Hine report on the processes and outcomes of care for Yorkshire’s
colorectal cancer patients. Br J Cancer. 2006;95(8):979–985.
13. Guidance on Commissioning Cancer Services: Improving Outcomes in
Gynaecological Cancers-The Mannual. Department of Health; 1999.
Available from: http://webarchive.nationalarchives.gov.uk/+/www.
dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPoli-
cyAndGuidance/DH_4005385. Accessed January 10, 2014.
14. The NHS Cancer Plan: a Plan for Investment, a Plan for Reform. Lon-
don: Department of Health; 2000. Available from: http://webarchive.
nationalarchives.gov.uk/+/www.dh.gov.uk/en/Publicationsandstatistics/
Publications/PublicationsPolicyandGuidance/DH_4009609. Accessed
January 10, 2014.
15. Characteristics of an Effective Multidisciplinary Team (MDT) [webpage
on the Internet]. London: National Cancer Intelligence Network; 2010.
Available from: http://www.ncin.org.uk/cancer_type_and_topic_
specific_work/multidisciplinary_teams/mdt_development. Accessed
January 10, 2014.
16. Kitchener HC. Gynaecological cancer services: time for change. BJOG.
1997;104(2):123–126.
17. Olaitan A, McCormack M. Centralisation of services for the management
of ovarian cancer: arguments for. BJOG. 2007;114(10):1188–1190.
18. Crawford SM, Brunskill PJ. Centralisation of services for the management
of ovarian cancer: arguments against. BJOG. 2007;114(10):1183–1185;
discussion 1186–1187.
19. Woo YL, Kyrgiou M, Bryant A, Everett T, Dickinson HO. Centralisation
of services for gynaecological cancer. Cochrane Database Syst Rev.
2012;3:CD007945.
20. United Kingdom Association of Cancer Registries Home Page [ homepage
on the Internet]. United Kingdom Association of Cancer Registries; 2013.
Available from: http://www.ukacr.org/. Accessed January 10, 2014.
21. National Institute for Health Care and Excellence. Ovarian Cancer:
the Recognition and Initial Management of Ovarian Cancer. Full
Guideline (Apr 2011). London: National Institute for Health Care and
Excellence; 2012. Available from: http://www.nice.org.uk/nicemedia/
live/13464/54266/54266.pdf. Accessed January 10, 2014.
22. McCluggage WG. My approach to and thoughts on the typing of ovarian
carcinomas. J Clin Pathol. 2008;61(2):152–163.
23. Pra t J; FIGO Committee on Gynecologic Oncology. Staging
classification for cancer of the ovary, fallopian tube, and peritoneum.
Int J Gynaecol Obstet. 2014;124(1):1–5.
24. Tortolero-Luna G, Mitchell MF. The epidemiology of ovarian cancer.
J Cell Biochem Suppl. 1995;23:200–207.
25. Kirwan J. Ovarian cancer standards of care. In: Acheson N, Luesly D,
editors. Gynaecological Oncology for the MRCOG and Beyond.
London: RCOG Press; 2010:115–143.
26. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics 2002. CA
Cancer J Clin. 2005;55(2):74–108.
27. Ovarian cancer risks and causes [webpage on the Internet]. London:
Cancer Research UK; 2013 [updated November 29, 2013]. Available
from: http://www.cancerresearchuk.org/cancer-help/type/ovarian-cancer/
about/ovarian-cancer-risks-and-causes. Accessed January 10, 2014.
28. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE. Risks of can-
cer in BRCA1 mutation carriers. Breast Cancer Linkage Consortium.
Lancet. 1994;343(8899):692–695.
29. Boyd J. Molecular genetics of hereditary ovarian cancer. Oncology
(Williston Park). 1998;12(3):399–406.
30. Easton DF, Ford D, Bishop DT. Breast and ovarian cancer incidence
in BRCA1 mutation carriers. Breast Cancer Linkage Consortium.
Am J Hum Genet. 1995;56(1):265–271.
31. Rosenthal A, Fraser L, Manchanda R, et al. Results of annual screening
in phase I of the United Kingdom familial ovarian cancer screening
study highlight the need for strict adherence to screening schedule.
J Clin Oncol. 2013;31(1):49–57.
32. Risch HA, Marrett LD, Howe GR. Parity, contraception, infertility,
and the risk of epithelial ovarian cancer. Am J Epidemiol. 1994;140(7):
585–597.
33. Adami HO, Hsieh CC, Lambe M, et al. Parity, age at first childbirth,
and risk of ovarian cancer. Lancet. 1994;344(8932):1250–1254.
34. Whittemore A, Harris R, Itnyre J. Characteristics relating to ovarian
cancer risk: collaborative analysis of 12 US case-control studies.
IV. The pathogenesis of epithelial ovarian cancer. Collaborative Ovarian
Cancer Group. Am J Epidemiol. 1992;136(10):1212–1220.
35. Hankinson SE, Colditz GA, Hunter DJ, et al. A prospective study of
reproductive factors and risk of epithelial ovarian cancer. Cancer.
1995;76(2):284–290.
36. Venn A, Watson L, Lumley J, Giles G, King C, Healy D. Breast and
ovarian cancer incidence after infertility and in vitro fertilization.
Lancet. 1995;346(8981):995–1000.
37. Vlahos NF, Economopoulos KP, Creatsas G. Fertility drugs and ovarian
cancer risk: a critical review of the literature. Ann N Y Acad Sci.
2010;1205:214–219.
38. Zreik TG, Ayoub CM, Hannoun A, Karam CJ, Munkarah AR. Fertility
drugs and risk of ovarian cancer: dispelling the myth. Curr Opin Obstet
Gynecol. 2008;20(3):313–319.
39. Tsilidis KK, Allen NE, Key TJ, et al. Oral contraceptive use and
reproductive factors and risk of ovarian cancer in the European Prospec-
tive Investigation into Cancer and Nutrition. Br J Cancer. 2011;105(9):
1436–1442.
40. Tworoger SS, Fairfield KM, Colditz GA, Rosner BA, Hankinson SE.
Association of oral contraceptive use, other contraceptive methods,
and infertility with ovarian cancer risk. Am J Epidemiol. 2007;166(8):
894–901.
41. Collaborative Group on Epidemiological Studies of ovarian Cancer,
Beral V, Doll R, Hermon C, Peto R, Reeves G. Ovarian cancer and oral
contraceptives: collaborative reanalysis of data from 45 epidemiological
studies including 23,257 women with ovarian cancer and 87,303 controls.
Lancet. 2008;371(9609):303–314.
42. Vessey MP, Painter R. Endometrial and ovarian cancer and oral
contraceptives- findings in a large cohort study. Br J Cancer.
1995;71(6):1340–1342.
43. McLaughlin JR, Risch HA, Lubinski J, et al; Hereditary Ovarian Cancer
Clinical Study Group. Reproductive risk factors for ovarian cancer in
carriers of BRCA1 or BRCA2 mutations: a case-control study. Lancet
Oncol. 2007;8(1):26–34.
44. Garg PP, Kerlikowske K, Subak L, Grady D. Hormone replacement
therapy and the risk of epithelial ovarian carcinoma: a meta-analysis.
Obstet Gynecol. 1998;92(3):472–479.

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International Journal of Women’s Health 2014:6 submit your manuscript | www.dovepress.com
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545
Clinical epidemiology of epithelial ovarian cancer in the UK
45. Beral V; Million Women Study Collaborators, Bull D, Green J, Reeves G.
Ovarian cancer and hormone replacement therapy in the Million Women
Study. Lancet. 2007;369(9574):1703–1710.
46. Modugno F, Ness RB, Allen GO, Schildkraut JM, Davis FG, Goodman MT.
Oral contraceptive use, reproductive history, and risk of epithelial
ovarian cancer in women with and without endometriosis. Am J Obstet
Gynecol. 2004;191(3):733–740.
47. Borgfeldt C, Andolf E. Cancer risk after hospital discharge diagnosis
of benign ovarian cysts and endometriosis. Acta Obstet Gynecol Scand.
2004;83(4):395–400.
48. Heaps JM, Nieberg RK, Berek JS. Malignant neoplasms arising in
endometriosis. Obstet Gynecol. 1990;75(6):1023–1028.
49. Melin AS, Lundholm C, Malki N, Swahn ML, Sparèn P, Berqqvist A.
Hormonal and surgical treatments for endometriosis and risk of epithe-
lial ovarian cancer. Acta Obstet Gynecol Scand. 2013;92(5):546–554.
50. Bergfeldt K, Rydh B, Granath F, et al. Risk of ovarian cancer in breast
cancer patients with a family history of breast or ovarian cancer:
a population based cohort study. Lancet. 2002;360(9337):891–894.
51. Ovarian cancer risk factors [webpage on the Internet]. Cancer Research
UK [Updated November 2013]. Available from: http://www.cancer re-
searchuk.org/cancer-info/cancerstats/types/ovary/riskfactors/. Accessed
March 31, 2014.
52. Chaturvedi AK, Engels EA, Gilbert ES, et al. Second cancers among
104,760 survivors of cervical cancer: evaluation of long term risk.
J Natl Cancer Inst. 2007;99(21):1634–1643.
53. Bates C. More women putting off starting a family as average age of
having a baby climbs to 29 [webpage on the Internet]. London: Mail
Online; October 20, 2011. Available from: http://www.dailymail.co.uk/
health/article-2051374/Average-age-women-having-baby-climbs-29-
start-family-later.html. Accessed January 10, 2014.
54. Olaitan A, Mocroft A, Jacobs I. Patterns in the incidence of age-
related ovarian cancer in South East England 1967–1996. BJOG.
2000;107(9):1094–1096.
55. Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence
and mortality in Europe in 2008. Eur J Cancer. 2010;46(4):765–781.
56. Ovarian cancer incidence statistics [webpage on the Internet]. London:
Cancer Research UK; 2011 [updated November 4, 2011]. Available
from: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/
ovary/incidence/uk-ovarian-cancer-incidence-statistics. Accessed
January 10, 2014.
57. Tate AR, Nicholson A, Cassell JA. Are GPs under investigating older
patients presenting with symptoms of ovarian cancer? Observational
Study using General Practice Research Database. Br J Cancer.
2010;102(6):947–951.
58. Walters S, Quaresma M, Coleman MP, Gordon E, Forman D, Rachet B.
Geographical variation in cancer survival in England, 1991–2006:
an analysis by Cancer Network. J Epidemiol Community Health.
2011;65(11):1044–1052.
59. Oberaigner W, Minicozzi P, Bielska-Lasota M, et al; Eurocare Working
Group. Survival for ovarian cancer in Europe: the across-country
variation did not shrink in the past decade. Acta Oncol. 2012;51(4):
441–453.
60. Differences in treatment for advanced ovarian cancer could explain
why UK survival lags behind other countries [webpage on the Internet].
London: Cancer Research UK; 2012 [updated October 3, 2012].
Available from: http://www.cancerresearchuk.org/about-us/cancer-
news/press-release/differences-in-treatment-for-advanced-ovarian-
cancer-could-explain-why-uk-survival-lags-behind-other. Accessed
January 10, 2014.
61. Short Term Ovarian Cancer Mortality [webpage on the Internet].
London: National Cancer Intelligence Network. Available from: http://
www.ncin.org.uk/publications/data_brief ings/short_term_ovarian_
cancer_mortality. Accessed January 10, 2014.
62. Morice P, Joulie F, Camatte S, et al. Lymph node involvement in
epithelial ovarian cancer: analysis of 276 pelvic and paraaortic lymph-
adenectomies and surgical implications. J Am Coll Surg. 2003;197(2):
198–205.
63. Chang SJ, Bristow RE, Ryu HS. Analysis of para-aortic lymphadenec-
tomy up to the level of the renal vessels in apparent early-stage ovarian
cancer. J Gynecol Oncol. 2013;24(1):29–36.
64. Olaitan A. NICE on ovarian cancer: Recommendations for detection in
primary care are flawed. BMJ. 2011;342:d3022.
65. Vergote I, Tropé CG, Amant F, et al; European Organization for
Research and Treatment of Cancer-Gynaecological Cancer Group;
NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary
surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363(10):
943–953.
66. Kehoe S, Hook J, Nankivell M, et al. Chemotherapy or upfront surgery
for newly diagnosed advanced ovarian cancer: results from the MRC
CHORUS trial. In: Proceedings of the 18th International Meeting of
the European Society of Gynaecological Oncology; October 19–22,
2013; Liverpool, UK. Abstract 5500.
67. Naik R, Edmondson RJ, Galaal K, Hatem MH, Godfrey KA. A statement
for extensive primary cytoreductive surgery in advanced ovarian cancer.
BJOG. 2008;115(13):1713–1714; author reply 1714.
68. Pomel C, Barton DP, McNeish I, Shepherd J. A statement for extensive
primary cytoreductive surgery in advanced ovarian cancer. BJOG.
2008;115(7):808–810.
69. Aletti GD, Dowdy SC, Gostout BS, et al. Aggressive surgical effort and
improved survival in advanced stage ovarian cancer. Obstet Gynecol.
2006;107(1):77–85.
70. Butler J, Gildea C, Meechan D, Nordin A. Ovarian Cancer Surgery by
Specialists in Specialist Centres. Proceedings of the 2011 UKacr/NCIN
conference: Liberating Information, Improving Outcomes; 2011 June
15–17; London, UK.