EUROPEAN UROLOGY 71 (2017) 96108

available at www.sciencedirect.com
journal homepage: www.europeanurology.com

Platinum Priority Review Bladder Cancer

Editorial by Marko Babjuk on pp. 109110 of this issue

Bladder Cancer Incidence and Mortality: A Global Overview and

Recent Trends

Sebastien Antoni a, Jacques Ferlay a, Isabelle Soerjomataram a, Ariana Znaor a, Ahmedin Jemal b,
Freddie Bray a,*
a
Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France; b Surveillance and Health Services Research, American Cancer
Society, Atlanta, GA, USA

Article info Abstract

Article history: Context: Bladder cancer has become a common cancer globally, with an estimated 430
Accepted June 8, 2016 000 new cases diagnosed in 2012.
Objective: We examine the most recent global bladder cancer incidence and mortality
Associate Editor: patterns and trends, the current understanding of the aetiology of the disease, and
James Catto specic issues that may inuence the registration and reporting of bladder cancer.
Evidence acquisition: Global bladder cancer incidence and mortality statistics are based
on data from the International Agency for Research on Cancer and the World Health
Keywords: Organisation (Cancer Incidence in Five Continents, GLOBOCAN, and the World Health
Bladder Organisation Mortality).
Evidence synthesis: Bladder cancer ranks as the ninth most frequently-diagnosed cancer
Cancer
worldwide, with the highest incidence rates observed in men in Southern and Western
Statistics Europe, North America, as well in certain countries in Northern Africa or Western Asia.
Incidence Incidence rates are consistently lower in women than men, although sex differences
Mortality varied greatly between countries. Diverging incidence trends were also observed by sex
in many countries, with stabilising or declining rates in men but some increasing trends
seen for women. Bladder cancer ranks 13th in terms of deaths ranks, with mortality rates
decreasing particularly in the most developed countries; the exceptions are countries
undergoing rapid economic transition, including in Central and South America, some
central, southern, and eastern European countries, and the Baltic countries.
Conclusions: The observed patterns and trends of bladder cancer incidence worldwide
appear to reect the prevalence of tobacco smoking, although infection with Schistosoma
haematobium and other risk factors are major causes in selected populations. Differences
in coding and registration practices need to be considered when comparing bladder
cancer statistics geographically or over time.
Patient summary: The main risk factor for bladder cancer is tobacco smoking. The
observed patterns and trends of bladder cancer incidence worldwide appear to reect
the prevalence of tobacco smoking.
# 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

* Corresponding author. Section of Cancer Surveillance, International Agency for Research on Cancer,
150 Cours Albert Thomas, 69372 Lyon Cedex 08, France. Tel. +33 4 72 73 84 53; Fax: +33 4 72 73 86 96.
E-mail address: brayf@iarc.fr (F. Bray).

http://dx.doi.org/10.1016/j.eururo.2016.06.010
0302-2838/# 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.
 EUROPEAN UROLOGY 71 (2017) 96108 97

1. Introduction GLOBOCAN, and World Health Organisation (WHO)

Bladder cancer is the ninth most common cancer world-
wide, with an estimated 430 000 new cases in 2012. More
than 60% of all bladder cancer cases and half of all the 165
000 bladder cancer deaths occur in the less developed
regions of the world. A strong male predominance is
observed with three-quarters of all bladder cancer cases
occurring in men [1].
While differences in the prevalence of tobacco smoking,
the main risk factor for the disease [2,3], explain much of
these geographical and sex disparities worldwide, infection
with Schistosoma haematobium reflects the high burden of
the disease in parts of Northern and sub-Saharan Africa
[4]. Equally, the scale of bladder cancer incidence can be
greatly affected by registration practices with respect to
the inclusion of noninvasive bladder tumours and multiple
tumours of the urinary tract, as part of routine reporting [5].
This paper provides an overview of the most recent
bladder cancer incidence and mortality patterns and trends
using the Cancer Incidence in Five Continents series (CI5),
Mortality databases held at the International Agency for
Research on Cancer (IARC). We review the current
understanding of the aetiology of the disease and the
specific issues that govern registration and reporting of
bladder cancer and how differences in such practices may
impact the comparison of cancer incidence statistics.
2. Evidence acquisition
2.1. Data sources
Regional and national bladder cancer incidence data and
corresponding populations were extracted from the CI5
series online [6]. CI5 is the main source of global cancer
incidence data provided by population-based cancer regis-
tries worldwide. The quality of data submitted to CI5 is
evaluated by a rigorous editorial process, ensuring that
compiled datasets reach the highest levels of validity,
completeness, and comparability [7]. Beginning over 50 yr
ago, the latest (10th) volume presents data for the period

Table 1 Estimated number of bladder cancer incident cases and deaths by region of the world in 2012 [1]

Area Incidence Mortality

Men Women M:F Men Women M:F

(n) (ASR) (n) (ASR) (ASR) (n) (ASR) (n) (ASR) (ASR)

World 330380 9.0 99413 2.2 4.1 123051 3.2 42033 0.9 3.6
By development level
More developed regions 196077 16.9 57766 3.7 4.6 58914 4.5 21024 1.1 4.1
Less developed regions 134303 5.3 41647 1.5 3.5 64137 2.6 21009 0.7 3.7
By human development level
Very high human development 183065 16.7 54713 3.9 4.3 51927 4.1 19760 1.1 3.7
High human development 56697 10.8 15596 2.2 4.9 24239 4.5 6588 0.8 5.6
Medium human development 79357 4.7 23748 1.2 3.9 39769 2.3 12226 0.6 3.8
Low human development 11096 3.1 5311 1.4 2.2 7065 2.1 3443 0.9 2.3
Africa 17685 6.3 6752 2.1 3.0 9362 3.5 3906 1.2 2.9
Eastern Africa 2824 3.3 1961 2.0 1.7 1819 2.2 1290 1.3 1.7
Sub-Saharan Africa 6460 3.0 4044 1.6 1.9 3873 1.9 2569 1.1 1.7
Middle Africa 610 2.2 441 1.3 1.7 420 1.6 300 0.9 1.8
Northern Africa 11225 15.1 2708 3.2 4.7 5489 7.6 1337 1.6 4.8
Southern Africa 1285 7.5 483 1.9 3.9 494 3.0 225 0.9 3.3
Western Africa 1741 2.1 1159 1.3 1.6 1140 1.5 754 0.9 1.7
Central and South America and Caribbean 17610 6.1 7234 2.0 3.1 7078 2.4 3069 0.8 3.0
Caribbean 1839 7.6 542 1.8 4.2 773 3.0 284 0.9 3.3
Central America 2327 3.4 1430 1.8 1.9 867 1.2 535 0.6 2.0
South America 13444 6.9 5262 2.1 3.3 5438 2.7 2250 0.9 3.0
North America 58089 19.5 18660 5.1 3.8 13285 4.0 5307 1.2 3.3
Asia 115646 5.5 32922 1.4 3.9 52816 2.5 16478 0.6 4.2
Eastern Asia 64662 5.8 20789 1.6 3.6 27271 2.3 10220 0.7 3.3
South-Eastern Asia 10784 4.3 3034 1.0 4.3 5352 2.2 1517 0.5 4.4
South-Central Asia 24415 3.6 6159 0.8 4.5 13413 2.0 3441 0.5 4.0
Western Asia 15785 19.0 2940 3.1 6.1 6780 8.4 1300 1.3 6.5
Europe 118365 17.7 32932 3.5 5.1 39522 5.2 12889 1.1 4.7
Central and Eastern Europe 30871 15.1 8904 2.7 5.6 13231 6.1 3543 0.9 6.8
Northern Europe 12722 12.4 4645 3.6 3.4 5174 4.4 2391 1.5 2.9
Southern Europe 34786 21.8 8049 3.8 5.7 11653 6.0 3001 1.0 6.0
Western Europe 39986 19.7 11334 4.3 4.6 9464 4.0 3954 1.1 3.6
Oceania 2985 10.6 913 2.7 3.9 988 3.2 384 1.0 3.2
Australia/New Zealand 2868 11.3 887 2.9 3.9 939 3.3 366 1.0 3.3
Melanesia 84 3.5 21 0.7 5.0 43 2.0 13 0.4 5.0
Micronesia/Polynesia 33 6.5 5 0.9 7.2 6 1.2 5 0.9 1.3

ASR = age-standardised rate.

98 EUROPEAN UROLOGY 71 (2017) 96108

20032007 [8]. To examine trends, we extracted the most
recent 15 yr of annual incidence data for each cancer
registry included in the CI5Plus database [9] and extended
this resource to other cancer registry reports and datasets
publicly available or online [1022]. Incidence data for
France and more updated regional European data were
obtained from the European Cancer Observatory database
[11]. Regional registry data were aggregated to obtain a
proxy of the (unknown) national incidence. Annual national
mortality data and corresponding populations were
extracted from the WHO Mortality database [23], while
cancer mortality by race in the US was extracted from the
Centres for Disease Control and Prevention [24].
[(Fig._1)TD$IG]
National bladder cancer incidence and mortality esti-
mates for the year 2012 were extracted from the
GLOBOCAN website [1]. GLOBOCAN provides national
estimates of incidence, mortality, and prevalence from
the best available data source in each country (often based
on data from CI5) utilising a hierarchical set of estimation
approaches [24]. To examine the burden in terms of
socioeconomic development, we utilised the Human
Development Index, a summary measure of key dimensions
of human development (health, education, and income)
categorised into four groups (low, medium, high, and very
high) [25] and the more and less developed regions as
defined in GLOBOCAN [1].

Fig. 1 Estimated age-standardised incidence rates for 184 countries of the world in 2012 in (A) men and (B) women [1].
 EUROPEAN UROLOGY 71 (2017) 96108 99

2.2. Data analyses
We computed age-standardised incidence and mortality
rates (ASR) for bladder cancer (International Classification
of Diseases [ICD]-10 code C67) by year/period, sex, and
region/country using the world standard population
[26]. To evaluate variations in the rates over time, we
computed the estimated annual percent change (EAPC)
and their 95% confidence intervals which are estimated
by fitting a simple linear model of the natural logarithm
of annual ASRs with time as a covariate [27]. In the
graphical presentation of the trends, curves were
[(Fig._2)TD$IG]
smoothed using lowess regression [28]. All analyses were
performed using R [29].
3. Evidence synthesis
3.1. World
According to GLOBOCAN estimates, about 430 000 new
bladder cancer cases and 165 000 bladder cancer deaths
occurred worldwide in 2012, with 75% of the total burden
occurring in men (Table 1). Substantial geographic varia-
tions can be observed, with 55% of all bladder cancer cases

Fig. 2 Estimated age-standardised mortality rates for 184 countries of the world in 2012 in (A) men and (B) women [23].
100 EUROPEAN UROLOGY 71 (2017) 96108
[(Fig._3)TD$IG]

Fig. 3 Age-standardised incidence (left) and mortality (right) rates of bladder cancer in men (top) and women (bottom) in selected countries in
20032007 (Egypt: 20042007). Regional incidence data from Gharbiah (Egypt), Blantyre (Malawi), Harare (Zimbabwe), Kampala (Uganda), Antofagasta
(Chile), Villa Clara (Cuba), Cali (Colombia), Quito (Ecuador), SEER (USA), Alberta, British Columbia, Manitoba, Northwest Territories, New Brunswick,
Nova Scotia, Prince Edward Island, Newfoundland and Labrador, Ontario, and Saskatchewan (Canada), Miyagi, Nagasaki, and Osaka (Japan), Hong Kong
and Shanghai (China), Chiang Mai (Thailand), Manila (Philippines), Chennai and Mumbai (India), Izmir (Turkey), Riyadh (Saudi Arabia), Cracow city,
 EUROPEAN UROLOGY 71 (2017) 96108
and 43% of bladder cancer deaths occurring in 20% of the
world population living in very high Human Development
Index (HDI) countries. In comparison, only 5% of the total
bladder cancer burden occurred in low HDI countries. Age-
standardised incidence rates therefore varied according to
sex and HDI, with the highest rates being found in men from
very high HDI countries (16.7 per 100 000) and the lowest in
women from low and medium HDI countries (Table 1).
ASR for both incidence and mortality were elevated in
North America and Europe (Table 1, Figs. 13). Some
countries in Western Asia and Northern Africa also reported
among the highest bladder cancer incidence and mortality
rates worldwide, particularly in men (Table 1, Figs. 13).
Overall, the lowest incidence and mortality rates were
found in Central and South America, Sub-Saharan Africa,
and South East Asia (Table 1, Figs. 13). Both the magnitude
of recent rates and the temporal patterns varied between
and within regions and by sex (Figs. 45), as summarised by
region below.
3.2. Europe
Europe has among the highest incidence rates of bladder
cancer in the world (Fig. 3). According to cancer registry
data, the highest incidence rates in men were recorded in
Southern Europe, particularly in Spain (regional data: ASR =
36.7 per 100 000) and Italy (regional data: ASR = 33.2 per
100 000). Incidence rates were also very high among men in
the Nordic countries (eg, Denmark: ASR = 27.4 per 100 000)
and in Western Europe (eg, Switzerland, regional data:
ASR = 26.2 per 100 000). Rates in men from Central and
Eastern European countries were intermediate (eg, Poland,
regional data: ASR = 20.2 per 100 000; Fig. 3). Since the mid-
to late-1990s, incidence rates have been stabilising or
decreasing in men from Western and Northern Europe
(other than in the Baltic countries), but increasing in
Southern, Central, and Eastern Europe (Fig. 4).
Mortality rates in European men were by far the highest
recorded worldwide, notably in Eastern Europe (eg, Poland:
ASR = 8.4 per 100 000), Southern Europe (eg, Spain:
ASR = 8.2 per 100 000), and in the Baltic countries (eg,
Latvia: ASR = 7.5 per 100 000). As observed with incidence,
mortality rates declined in men in most European countries,
although small increases were observed in a few Southern
and Eastern European countries (eg, Slovenia, Croatia, and
Bulgaria) and in the Baltic countries (Figs. 4 and 5).
In women, the highest incidence rates were observed in
Denmark (ASR = 8.4 per 100 000), Norway (ASR = 6.4 per 100
000), and Switzerland (regional data: ASR = 6.3 per 100 000).
Rates in women increased in many European countries from
the mid-1990s, particularly in Central and Eastern Europe
(eg, Bulgaria; EAPC = +5.5%), Southern Europe (eg, Slovenia,
Kielce, and Lower Silesia (Poland), St. Petersburg (Russian Federation), Granada, Murcia, Navarra, and Tarragona (Spain), City of Torino, Modena,
Parma, Romagna, Ragusa, and Varese provinces (Italy), Geneva and St. Gall-Appenzell (Switzerland), Berlin, Brandenburg, Mecklenburg, Saxony,
Saxony-Anhalt, Schleswig-Holstein, and Thuringia (Germany), Doubs, Isere, Haut-Rhin, Herault, and Tarn (France), Australian Capital Territory, New
South Wales, Northern Territory, Queensland, South Australia, Tasmania, Victoria, and Western Australia (Australia). Data from Cuba are presented
with Central and South America.
F = female; M = male.
101
EAPC = +3.5%), and the Baltic countries (eg, Latvia,
EAPC = +2.7%). In contrast, stabilising or slightly decreasing
rates were observed in Northern European women (Fig. 4).
As with incidence, Danish women had the highest
mortality rates in Europe (ASR = 2.3 per 100 000), although
these rates decreased by 2.3% annually between 1998 and
2012 (Figs. 4 and 5). Mortality decreases were generally
observed in most regions of Europe, with several Western
European countries (eg, Germany: EAPC = 2.1%) exhibiting
declines of a similar magnitude to those observed in
Denmark (Figs. 4 and 5).
3.3. Northern America
The highest incidence was observed among US White men
(regional data: ASR = 22.8 per 100 000), a rate two-fold
higher than in their Black counterparts (ASR = 11.7 per 100
000). A similar pattern was observed in women, although
the difference between races was less remarkable (Fig. 3).
Incidence rates in the region decreased from the mid-1990s,
except for a slight nonsignificant increase in US Black men
(Fig. 4). Mortality was higher in US White men
(ASR = 3.9 per 100 000) than in Blacks (ASR = 2.8 per 100
000), but slightly higher in Black than in White women
(Fig. 3). Overall, mortality has been stable or slightly
decreasing in the North American populations under study
in recent years (Figs. 4 and 5). Canadian incidence and
mortality rates are intermediate to those of USA Blacks and
Whites.
3.4. Asia
Two different patterns can be observed in Asia: relatively
low incidence and mortality rates in Central and Eastern
Asia contrasting with very high incidence and mortality
rates in Western Asia (Figs. 13). Japanese men had the
highest incidence rates in Central and Eastern Asia (regional
data: ASR = 9.6 per 100 000) followed by Korean men
(ASR = 9.4 per 100 000). These were lower than rates
recorded in any European men in our study. In contrast,
incidence rates in men from Turkey were among the highest
worldwide (regional data: ASR = 26.4 per 100 000), as were
those observed in Israeli men (ASR = 25.1 per 100 000).
Israeli women also had the highest incidence rates in
Western Asia (ASR = 4.5 per 100 000), almost double the
highest rate recorded in Central and Eastern Asian women
(Thailand, regional data: ASR = 2.3 per 100 000). Mortality
rates in Israel were also higher than in countries of Central
and Eastern Asia included in our analyses for both men and
women (Fig. 3). Incidence and mortality rates have been
relatively stable or decreasing in most Asian countries in
both sexes (Figs. 4 and 5).
102 EUROPEAN UROLOGY 71 (2017) 96108
[(Fig._4)TD$IG]

Fig. 4 Estimated annual percent change in age-standardised incidence (left) and mortality (right) rates of bladder cancer in men (top) and women
(bottom) in selected countries (last 15 yr of available data). Regional incidence data from Gharbiah (Egypt), Blantyre (Malawi), Harare (Zimbabwe),
Kampala (Uganda), Antofagasta (Chile), Villa Clara (Cuba), Cali (Colombia), Quito (Ecuador), SEER (USA), Alberta, British Columbia, Manitoba, Northwest
Territories, New Brunswick, Nova Scotia, Prince Edward Island, Newfoundland and Labrador, Ontario, and Saskatchewan (Canada), Miyagi, Nagasaki,
and Osaka (Japan), Hong Kong and Shanghai (China), Chiang Mai (Thailand), Manila (Philippines), Chennai and Mumbai (India), Izmir (Turkey), Riyadh
(Saudi Arabia), Cracow City, Kielce, and Lower Silesia (Poland), St Petersburg (Russian Federation), Granada, Murcia, Navarra, and Tarragona (Spain),
 EUROPEAN UROLOGY 71 (2017) 96108
3.5. Central and South America and the Caribbean
Incidence rates in this region were relatively low, although
rates were elevated in some countries in men (eg, Uruguay:
ASR = 15.8 per 100 000). Incidence in Chile was very high
in men (regional data: ASR = 17.6 per 100 000) but also in
women (ASR = 9.8 per 100 000, the highest rates recorded in
women in our study). Overall, incidence rates remained
stable in the region since 1993 apart from a 4.5% annual
increase in Ecuadorian women. Mortality was generally low
compared with other regions of the world (Fig. 3), although
increases were observed in recent years for both sexes in
some countries (eg, Cuba and Brazil; Figs. 4 and 5).
3.6. Africa
Bladder cancer incidence rates in Africa were among the
lowest worldwide (Figs. 1 and 3, Table 1), with some notable
exceptions such as Egyptian men (regional data:
ASR = 19.0 per 100 000) or women from Malawi (regional
data: ASR = 9.2 per 100 000; second highest incidence rates
in women in our study). Bladder cancer mortality rates in
Egyptian men were relatively high (ASR = 5.6 per 100 000)
although these rates decreased sharply in recent years
(EAPC = 4.0%; Fig. 4).
3.7. Oceania
Incidence rates in Australia and New Zealand were
comparable to those of other very high HDI countries in
Asia (eg, Japan and Korea) but much lower than those
observed in Europe or North America (Fig. 3). Mortality
rates were comparable to those observed in the US,
however, particularly in men (Fig. 3). Both incidence and
mortality rates decreased by about 2% annually since the
mid-1990s in both countries and in both sexes; the decline
in incidence in New Zealand was more rapid, with an EAPC
of 7.2% in men and 6.2% in women (Figs. 4 and 5).
4. Conclusions
In this study, we presented the most recent patterns and
trends of bladder cancer worldwide, observing the highest
incidence rates of disease in countries with very high levels
of human development in Europe and Northern America, but
also, likely for differing reasons, in parts of Northern Africa
and Western Asia. The burden was greater in men, yet
diverging incidence trends by sex were observed in some
countries, with rate declines in men and increases in women.
Overall, bladder cancer mortality has been decreasing except
in countries undergoing rapid economic transition in Central
and South America, in some central, southern, and eastern
European countries, and in the Baltic countries.
City of Torino, Modena, Parma, Romagna, Ragusa, and Varese provinces (Italy), Geneva and St. Gall-Appenzell (Switzerland), Berlin, Brandenburg,
Mecklenburg, Saxony, Saxony-Anhalt, Schleswig-Holstein, and Thuringia (Germany), Doubs, Isere, Haut-Rhin, Herault, and Tarn (France), Australian
Capital Territory, New South Wales, Northern Territory, Queensland, South Australia, Tasmania, Victoria, and Western Australia (Australia). Data from
Cuba are presented with Central and South America.
a
A change significantly different than 0.
103
The main risk factor for bladder cancer is tobacco
smoking; ever-smokers are considered to have a 2.5 times
higher risk for this cancer than nonsmokers [30]. In various
populations, tobacco has been found to be responsible for
about half of all bladder cancer cases [3133] and 40% of all
bladder cancer deaths [32]. In this context, it is not
surprising to see bladder cancer incidence and mortality
patterns and trends (Fig. 1) partially mirroring correspond-
ing smoking histories [3]. Indeed, the natural history of the
disease must also be considered: current bladder cancer
patterns reflect tobacco smoking prevalence over 2030 yr
ago [34]. Thus, the very high bladder cancer incidence rates
observed, for example, among US and Spanish men (as in
many very high HDI countries) are likely to be the
consequence of a very high smoking prevalence in these
countries in the 1970s and 1980s. According to National
Health Surveys, 42% of US adults were reported to be
smokers in 1965 [35] while 63% of Spanish men were active
smokers in 1978 [36]. Smoking prevalence in men has
markedly decreased over the past several decades in North
America and many European countries, which may explain
the decrease in bladder cancer incidence and mortality
observed in these regions. However, in other regions of the
world, such as the growing economies of Central and South
America or some Central and Eastern European countries,
smoking prevalence began to decrease more recently,
started to level off, or is still increasing (in particular in
women) [37], suggesting that decreases in bladder cancer
incidence and mortality will not be observed in these
regions for another few decades.
In Egypt, bladder cancer has long been the most
commonly diagnosed cancer because of its association with
schistosomiasis, a disease caused by parasitic worms
(S. haematobium) in the urinary tract, and endemic in this
region [5,38]. Schistosomiasis-associated bladder cancers are
predominantly squamous cell carcinomas, a histologic
subtype that is relatively rare in the lower urinary tract
where most cancers are typically transitional cell carcinomas
[5,39]. Although there likely remains a role for S. haemato-
bium in the high incidence of bladder cancer in Egypt, there
has been a marked decrease in the incidence of squamous cell
carcinomas of the bladder in recent years, while transitional
cell carcinomas incidence has been increasing, particularly in
men [4042], probably due to a reduction in Schistosoma
infection and increases in the prevalence of cigarette
smoking. Recent tobacco smoking statistics showed a very
high prevalence in Egyptian men (56% in 2005) and a very low
prevalence in women (<1% in ever-married women aged
1549 yr) [43]. Women in Malawi had the highest incidence
rates in our study, similar to those observed in men. Given the
large differences in smoking prevalence between men and
women in this country (ie, 26.3% and 6.3% in men and
women, respectively) [44], other risk factors may be in
104 EUROPEAN UROLOGY 71 (2017) 96108
[(Fig._5)TD$IG]
Northern Europe Western Europe Southern Europe
10 Denmark 10 Austria 10 Croatia
Finland France Greece
Age-standardised mortality rates (per 100 000)

Age-standardised mortality rates (per 100 000)

Age-standardised mortality rates (per 100 000)

Norway Germany Italy
UK Netherlands Spain
5 5 5

3 3 3

2 2 2

1 1 1

0.5 0.5 0.5

0.2 0.2 0.2

0.1 0.1 0.1

1940 1960 1980 2000 1940 1960 1980 2000 1940 1960 1980 2000

Central and Eastern Europe North America Oceania

10 Bulgaria 10 Canada 10 Australia
Age-standardised mortality rates (per 100 000)

Age-standardised mortality rates (per 100 000)

Age-standardised mortality rates (per 100 000)

Czech Rep. USA: White New Zealand
Hungary USA: Black
Romania
5 5 5

3 3 3

2 2 2

1 1 1

0.5 0.5 0.5

0.2 0.2 0.2

0.1 0.1 0.1

1940 1960 1980 2000 1940 1960 1980 2000 1940 1960 1980 2000

Central & South America Eastern & South Eastern Asia Western Asia
10 Argentina 10 Japan 10 Israel
Brazil Rep. of Korea
Age-standardised mortality rates (per 100 000)

Age-standardised mortality rates (per 100 000)

Age-standardised mortality rates (per 100 000)

Chile Singapore
Cuba
5 5 5

3 3 3

2 2 2

1 1 1

0.5 0.5 0.5

0.2 0.2 0.2

0.1 0.1 0.1

1940 1960 1980 2000 1940 1960 1980 2000 1940 1960 1980 2000

Fig. 5 Time trends in bladder cancer mortality in men (straight line) and women (dashed line) for selected countries grouped by world regions,
presented on a logarithmic scale. Data from Cuba are presented with Central and South America.
Rep. = Republic.
 EUROPEAN UROLOGY 71 (2017) 96108
[(Fig._6)TD$IG]
30
Age-standardised rates per 100 000
25
20
15
10
1970
Fig. 6 Time trends in bladder cancer incidence (orange) and mortality (blue) in Scotland, UK (dashed line) and the US (straight line), in men.
ENCR = European Network of Cancer Registries; IACR = International Agency for Research on Cancer; SEER = Surveillance, Epidemiology, and End
Results.
operation. However, the evidence for a role of schistosomia-
sis in Malawi remains limited [45].
Exposure to aromatic amines and other chemicals
affecting workers in the painting, rubber, or aluminium
industries have been classified as carcinogenic to the
bladder [46]. Many other occupational exposures are also
considered likely to cause bladder cancer [46,47]. In a recent
review, 7.1% of all bladder cancers in men (1.9% in women)
in the UK were attributed to occupational exposure to
carcinogens [48]. However, the global impact of occupa-
tional exposures on bladder cancer incidence remains
difficult to assess and is likely to be relatively limited [49].
Large scale population exposures to environmental risk
factors may also be implicated. For example, high levels of
arsenic in the drinking water of the city of Antofagasta in
Chile have been reported to significantly increase the risk
for urinary tract cancers [50,51] and may explain some of
the high incidence rates observed in this region (Fig. 3).
However, such assumptions are difficult to validate given
the strong confounder effect of tobacco smoking in Chile
where smoking rates are high (32.1% in men and 26.3% in
women in 2015) [37].
Inherited genetic factors are also believed to play a role
in bladder cancer carcinogenesis [2,52]. For example, slow
acetylation of N-acetyltransferase 2, a key enzyme in
aromatic amines metabolism, is considered to increase
susceptibility to tobacco smoke, polycyclic aromatic hydro-
carbons, or other occupational carcinogens [2]. However,
results remain inconsistent [53] and further research is
needed on the association between polymorphisms in the
different carcinogen metabolising enzymes and bladder
cancer risk. In our study, we observed disparities in the
burden of bladder cancer between the White and Black
populations of the US but these are more likely to reflect risk
determinants linked to socio-economic disparities than
population variations in genetic factors [54].
An increased risk of developing and dying from bladder
cancer has been reported in patients with type-2 diabetes
treated with pioglitazone [55]. This led to the classification
of this drug as probably carcinogenic to the human bladder
105
Incidence
ENCR/IACR recommendations
Mortality
USA (SEER)
UK, Scotland
1980 1990 2000 2010
by the IARC Monographs in 2013 [56]. However, the
contribution of this drug to the overall burden of bladder
cancer at the population level is likely to be limited [5759].
We cannot discount other factors that may influence
bladder cancer rates and the extent of their comparability at
the international level. Given the limited accuracy of current
biomarkers for early stage bladder cancer, the difficulty in
identifying a high-risk target population, and the potential
harm caused to the patients by false positives/negatives,
most urological societies do not recommend population-
based screening for bladder cancer [60,61], and thus will not
have impacted upon the results presented here.
Differences in terms of healthcare systems, treatment
protocols, or access to diagnosis and treatment facilities,
particularly between countries at different levels of devel-
opment of resource levels, could partly explain the
differences observed in bladder cancer survival and mortali-
ty rates between countries [62,63]. Treatment options for
bladder cancer depend largely on stage at diagnosis and
usually include transurethral resection of the tumour
followed by partial or radical cystectomy, intravesical
immunotherapy or chemotherapy, or systemic chemother-
apy with or without radiotherapy [64,65]. Improvements in
treatment may increase survival and reduce mortality rates
[66], and may explain the declines in bladder cancer
mortality observed in men in several high-income countries.
However, survival from bladder cancer has held steady since
1990 in countries such as Norway; 5-yr relative survival
among men was 73% and 76% for diagnoses in 19941998
and 20092013, respectively [10,67], indicating recent
mortality decreases in such high-income countries are for
reasons other than changes in treatment procedures.
Evaluating temporal variations of the bladder cancer
burden also requires particular care and awareness of
the different coding and registration practices that can
create artefacts and altered trends, particularly in incidence
[5]. Until ICD-7, the distinction between bladder and other
urinary tract cancers was made on the fourth digit (181.0 for
bladder, 181.7 for other organs of the urinary tract) [5]. As the
fourth digit was sometimes not available when results were
106 EUROPEAN UROLOGY 71 (2017) 96108
reported, it could lead to a certain level of uncertainty
regarding the proportion of urinary cancers that occurred in
the bladder. However, this specific issue should not affect our
results as data included in this study were recorded at a time
where more recent classification schemes (eg, ICD-9 and
ICD-O-1) were being used in most countries. Changes in
disease classification can also impact the stability of the rates
over time, although our results should not be affected given
the short time-spam of our data (eg, starting early 1990s). In
a European study, this potential artefact was found to have
no significant impact on bladder cancer mortality [68].
Certainly the most important factor related to registra-
tion practices is the coding and reporting of noninvasive
(in-situ) tumours. Since they can often represent a large
proportion of all bladder tumours [69], their inclusion
(or otherwise) strongly affects comparability between
datasets and in a single population over time. Figure 6
presents bladder cancer incidence and mortality trends in
men in Scotland [70] and the USA (Surveillance, Epidemiol-
ogy, and End Results [SEER]) [19] and illustrates this
problem. In the USA, all in-situ tumours of the bladder
have been consistently reported as invasive. This resulted in
relatively high and stable incidence rates and a low mortality
to incidence ratio. In Scotland, nonmalignant tumours of the
bladder were also recoded as invasive bladder cancer until
the mid-1990s. New European and national coding guide-
lines were then released, with a recommendation to code
these tumours as neoplasms of uncertain behaviour or
carcinomas in situ whenever possible [70]. This resulted in a
sudden drop in overall bladder cancer incidence rates. As
most of the noninvasive tumours are associated with a good
prognosis, mortality rates are less affected by differences in
registration practices. This indicator may thus be of greater
utility in measuring and comparing geographical and
temporal variations in bladder cancer and overall progress
in combating the disease at the population level.
Multiple tumours occurring in the same individual could
also be an issue when examining bladder cancer statistics.
Since the implementation of the most recent IARC/IACR
rules [71], bladder and other urothelial cancers are
considered as a single entity for the purpose of counting
multiple primary tumours. This implies that if an urothelial
tumour appears first in the renal pelvis or the ureter, any
subsequent bladder cancer in the same person will be
recorded by the registry but not reported for statistical
purposes [5]. The same situation may arise if a noninvasive
bladder tumour is recorded prior to a malignant bladder
tumour in the same individual.
The main strength of this study is the use of cancer
incidence and mortality data from official databases held at
IARC and WHO and based on high quality national or
regional population-based cancer registries and national
vital registration systems. However, our results are limited
by the availability of high quality cancer data in certain
areas of the world. Sixty-eight countries provided high-
quality regional or national incidence data for the most
recent volume of CI5 [8], while high quality national
mortality data were only available in 34 of 194 WHO
member states [72]. In other countries, as well as in
countries where national data are not available, GLOBO-
CAN 2012 estimates are the main source of information on
the burden of cancer. These estimates are based on the best
data available in each country and a set of estimation
methods with variable levels of accuracy depending on the
setting and cancer site. In a recent validation study,
estimates for bladder cancer in Norway were found to
range from 15% lower to 22% higher than recorded data,
depending on the method used [73]. This discrepancy is,
however, likely to be greater in countries with lower
quality of cancer registry data.
In this study we examined the most recent global figures
of bladder cancer incidence and mortality from official
databases held at IARC and WHO, based on high-quality
national or regional population-based cancer registries and
national vital registration systems. Our study illustrates
the impact of the tobacco epidemic in different regions of
the world with high but often decreasing incidence in
countries with a very high HDI, particularly in men, and
lower but still increasing rates in countries with rapidly
transitioning economies, particularly in women. Despite
diverging trends by sex in many countries, bladder cancer
remains a cancer diagnosed predominantly in men. Our
results also indicate that the burden of bladder cancer
associated with S. haematobium infection may have
decreased in some African countries. Finally, we described
several coding and registration issues that affect the
computation and comparison of bladder cancer statistics.
In particular, efforts should be made to harmonise the
coding of noninvasive tumours of the bladder to improve
international comparability of bladder cancer incidence,
mortality, and survival statistics.
Author contributions: Freddie Bray had full access to all the data in the
study and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Antoni, Znaor, Bray.
Acquisition of data: Antoni, Ferlay.
Analysis and interpretation of data: Antoni, Bray.
Drafting of the manuscript: Antoni, Ferlay, Soerjomataram, Znaor, Jemal,
Bray.
Critical revision of the manuscript for important intellectual content:
Antoni, Ferlay, Soerjomataram, Znaor, Jemal, Bray.
Statistical analysis: Antoni.
Obtaining funding: None.
Administrative, technical, or material support: None.
Supervision: None.
Other: None.
Financial disclosures: Freddie Bray certies that all conicts of interest,
including specic nancial interests and relationships and afliations
relevant to the subject matter or materials discussed in the manuscript
(eg, employment/afliation, grants or funding, consultancies, honoraria,
stock ownership or options, expert testimony, royalties, or patents led,
received, or pending), are the following: None.
Funding/Support and role of the sponsor: None.
Acknowledgments: We would like to thank the directors and staff of
cancer registries around the world who compiled the data used in
this paper: regional registries of Alberta, British Columbia, Manitoba,
 EUROPEAN UROLOGY 71 (2017) 96108
Northwest Territories, New Brunswick, Nova Scotia, Prince Edward
Island, Newfoundland and Labrador, Ontario, and Saskatchewan
(Canada), Antofagasta (Chile), Hong Kong and Shanghai (China), Cali
(Colombia), Villa Clara (Cuba), Quito (Ecuador), Doubs, Isere, Haut-Rhin,
Herault and Tarn (France), Gharbiah (Egypt), Berlin, Brandenburg,
Mecklenburg, Saxony, Saxony-Anhalt, Schleswig-Holstein, and Thur-
ingia (Germany), Chennai and Mumbai (India), City of Torino, Modena,
Parma, Romagna, Ragusa, and Varese provinces (Italy), Miyagi, Nagasaki,
and Osaka (Japan), Blantyre (Malawi), Manila (Philippines), Cracow city,
Kielce, and Lower Silesia (Poland), St. Petersburg (Russian Federation),
Granada, Murcia, Navarra, and Tarragona (Spain), Geneva and St. Gall-
Appenzell (Switzerland), Chiang Mai (Thailand), Izmir (Turkey), Kampala
(Uganda), SEER registries (USA), Harare (Zimbabwe), state and territory
cancer registries of Australia, and national registries of Austria, Belarus,
Bulgaria, Costa Rica, Croatia, Czech Republic, Denmark, Estonia, Finland,
Iceland, Ireland, Israel, Republic of Korea, Latvia, Lithuania, The
Netherlands, New Zealand, Norway, Saudi Arabia, Singapore, Slovakia,
Slovenia, Sweden, UK, and Uruguay.
References
[1] GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide:
IARC CancerBase No. 11. International Agency for Research on
Cancer Web site. http://globocan.iarc.fr.
[2] Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk factors
of urothelial bladder cancer. Eur Urol 2013;63:23441.
[3] Ng M, Freeman MK, Fleming TD, et al. Smoking prevalence and
cigarette consumption in 187 countries, 1980-2012. JAMA
2014;311:18392.
[4] Parkin DM. The global health burden of infection-associated can-
cers in the year 2002. Int J Cancer 2006;118:303044.
[5] Parkin DM. The global burden of urinary bladder cancer. Scand J
Urol Nephrol Suppl 2008;218:1220.
[6] Cancer incidence in ve continents, Vol. IX. International Agency
for Research on Cancer Web site. http://ci5.iarc.fr/CI5I-X.
[7] Bray F, Ferlay J, Laversanne M, et al. Cancer incidence in ve
continents: Inclusion criteria, highlights from Volume X and the
global status of cancer registration. Int J Cancer 2015;137:206071.
[8] Forman D, Bray F, Brewster DH, et al. Cancer incidence in ve
continents, X. Lyon, France: IARC; 2013.
[9] Cancer incidence in ve continents, CI5plus. IARC CancerBase No.
9. International Agency for Research on Cancer Web site. http://ci5.
iarc.fr.
[10] NORDCAN: Cancer incidence, mortality, prevalence and survival in
the Nordic Countries, Version 7.1. Association of the Nordic Cancer
Registries. Danish Cancer Society Web site. http://www.ancr.nu.
[11] European Cancer Observatory: Cancer incidence, mortality, preva-
lence and survival in Europe. European Network of Cancer Regis-
tries, International Agency for Research on Cancer Web site. http://
eco.iarc.fr/.
[12] Croatian National Cancer Registry. Cancer in Croatia 2012 Web site.
http://www.hzjz.hr/sluzbe/sluzba-za-epidemiologiju/odjel-za-
nadzor-i-istrazivanje-ne-zaraznih-bolesti/odsjek-za-zlocudne-
bolesti-s-registrom-za-rak.
[13] Czech National Cancer Registry. Cancer incidence 2010 in the Czech
Republic Web site. http://www.uzis.cz/.
[15] Dimitrova N, Vukov M, Valerianova Z. Report cancer incidence in
Bulgaria 2011. Soa, Bulgaria: Bulgarian National Cancer Registry;
2013.
[16] National Cancer Registry Ireland Web site. http://www.ncri.ie/.
[17] Moscow Research Oncological Institute, Russian Federation Web
site. http://www.oncology.ru.
[18] UK, England, Ofce for National Statistics Web site. http://www.
ons.gov.uk/ons/.
107
[19] Surveillance, Epidemiology, and End Results Program Research
Data (1973-2012), National Cancer Institute, DCCPS, Surveillance
Research Program, Surveillance Systems Branch Web site. http://
seer.cancer.gov/.
[20] Republic of Korea National Cancer Centre Web site. http://www.
ncc.re.kr/english/infor/kccr.jsp.
[21] Australian Cancer Database. Australian Institute of Health and
Welfare Web site. http://www.aihw.gov.au.
[22] New Zealand National Ministry of Health Web site. http://www.
nzhis.govt.nz.
[23] WHO Mortality Database World Health Organisation Web site.
http://www.who.int/healthinfo/statistics/mortality_rawdata/en/
index.html.
[24] Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and
mortality worldwide: sources, methods and major patterns in
GLOBOCAN 2012. Int J Cancer 2015;136:E35986.
[25] United Nations Development Programme. Human Development In-
dex (HDI) Web site. http://hdr.undp.org/en/content/human-
development-index-hdi.
[26] Segi M. Cancer mortality for selected sites in 24 countries (1950-
57). Sendai, Japan: Department of Public Health, Tohoku University
of Medicine; 1960.
[27] Clegg LX, Hankey BF, Tiwari R, Feuer EJ, Edwards BK. Estimating
average annual per cent change in trend analysis. Stat Med
2009;28:367082.
[28] Loader C. Smoothing: Local Regression Techniques Web site. http://
hdl.handle.net/10419/22186.
[29] R Development Core Team. R: A language and environment
for statistical computing [computer programme]. Vienna, Austria:
R Foundation for Statistical Computing; 2014.
[30] Cumberbatch MG, Rota M, Catto JW, La VC. The role of tobacco
smoke in bladder and kidney carcinogenesis: A comparison of
exposures and meta-analysis of incidence and mortality risks.
Eur Urol 2016;70:45866.
[31] Freedman ND, Silverman DT, Hollenbeck AR, Schatzkin A, Abnet CC.
Association between smoking and risk of bladder cancer among
men and women. JAMA 2011;306:73745.
[32] Park S, Jee SH, Shin HR, et al. Attributable fraction of tobacco
smoking on cancer using population-based nationwide cancer
incidence and mortality data in Korea. BMC Cancer 2014;14:406.
[33] Agudo A, Bonet C, Travier N, et al. Impact of cigarette smoking on
cancer risk in the European prospective investigation into cancer
and nutrition study. J Clin Oncol 2012;30:45507.
[34] Moolgavkar SH, Stevens RG. Smoking and cancers of bladder and
pancreas: risks and temporal trends. J Natl Cancer Inst 1981;
67:1523.
[35] Centres for Disease Control and Prevention. Trends in current
cigarette smoking among high school students and adults, United
States, 1965-2011. Centres for Disease Control and Prevention Web
site. http://www.cdc.gov/tobacco/data_statistics/tables/trends/
cig_smoking.
[36] Regidor E, Gutierrez-Fisac JL, de lS I, Fernandez E. Trends in princi-
pal cancer risk factors in Spain. Ann Oncol 2010;21(Suppl 3),
iii37-42.
[37] Eriksen M, Mackay J, Schluger N, Islami Gomeshtapeh F, Drope J.
The tobacco atlas. 5. Atlanta, GA: American Cancer Society;
2015.
[38] Steinmann P, Keiser J, Bos R, Tanner M, Utzinger J. Schistosomiasis
and water resources development: systematic review, meta-
analysis, and estimates of people at risk. Lancet Infect Dis
2006;6:41125.
[39] Parkin DM, Sitas F, Chirenje M, Stein L, Abratt R, Wabinga H. Part I:
Cancer in indigenous Africansburden, distribution, and trends.
Lancet Oncol 2008;9:68392.
108 EUROPEAN UROLOGY 71 (2017) 96108
[40] Salem HK, Mahfouz S. Changing patterns (age, incidence, and
pathologic types) of schistosoma-associated bladder cancer in
Egypt in the past decade. Urology 2012;79:37983.
[41] Felix AS, Soliman AS, Khaled H, et al. The changing patterns of
bladder cancer in Egypt over the past 26 years. Cancer Causes
Control 2008;19:4219.
[42] Gouda I, Mokhtar N, Bilal D, El-Bolkainy T, El-Bolkainy NM. Bilhar-
ziasis and bladder cancer: a time trend analysis of 9843 patients.
J Egypt Natl Canc Inst 2007;19:15862.
[43] El-Zanaty F, Way AA. Report Egypt Demographic and Health Survey
2005. Cairo, Egypt: Ministry of Health and Population, National
Population Council, El-Zanaty and Associates, and ORC Macro; 2006.
[44] World Health Organisation. WHO Report on the Global Tobacco
Epidemic, Country prole: Malawi Web site. http://www.who.int/
tobacco/surveillance/policy/country_prole/mwi.pdf.
[45] Makaula P, Sadalaki JR, Muula AS, Kayuni S, Jemu S, Bloch P.
Schistosomiasis in Malawi: A systematic review. Parasit Vectors
2014;7:570.
[46] Cogliano VJ, Baan R, Straif K, et al. Preventable exposures associated
with human cancers. J Natl Cancer Inst 2011;103:182739.
[47] Vlaanderen J, Straif K, Ruder A, et al. Tetrachloroethylene exposure
and bladder cancer risk: a meta-analysis of dry-cleaning-worker
studies. Environ Health Perspect 2014;122:6616.
[48] Rushton L, Hutchings SJ, Fortunato L, et al. Occupational cancer
burden in Great Britain. Br J Cancer 2012;107(Suppl 1):S37.
[49] Purdue MP, Hutchings SJ, Rushton L, Silverman DT. The proportion
of cancer attributable to occupational exposures. Ann Epidemiol
2015;25:18892.
[50] Marshall G, Ferreccio C, Yuan Y, et al. Fifty-year study of lung and
bladder cancer mortality in Chile related to arsenic in drinking
water. J Natl Cancer Inst 2007;99:9208.
[51] Steinmaus CM, Ferreccio C, Romo JA, et al. Drinking water arsenic in
northern chile: high cancer risks 40 years after exposure cessation.
Cancer Epidemiol Biomarkers Prev 2013;22:62330.
[52] Antonova O, Toncheva D, Grigorov E. Bladder cancer risk from the
perspective of genetic polymorphisms in the carcinogen metabo-
lising enzymes. J BUON 2015;20:1397406.
[53] Pesch B, Gawrych K, Rabstein S, et al. N-acetyltransferase 2 pheno-
type, occupation, and bladder cancer risk: results from the EPIC
cohort. Cancer Epidemiol Biomarkers Prev 2013;22:205565.
[54] Jacobs BL, Montgomery JS, Zhang Y, Skolarus TA, Weizer AZ,
Hollenbeck BK. Disparities in bladder cancer. Urol Oncol 2012;
30:818.
[55] Report Caisse nationale de lassurance maladie. Risque de cancer de
la vessie chez les personnes diabetiques traitees par pioglitazone en
France: une etude de cohorte sur les donnees du SNIIRAM et du
PMSI,;1; 2011. January 7, 2016; Paris, France.
[56] Grosse Y, Loomis D, Lauby-Secretan B, et al. Carcinogenicity of some
drugs and herbal products. Lancet Oncol 2013;14:8078.
[57] Lewis JD, Habel LA, Quesenberry CP, et al. Pioglitazone use and risk
of bladder cancer and other common cancers in persons with
diabetes. JAMA 2015;314:26577.
[58] Levin D, Bell S, Sund R, et al. Pioglitazone and bladder cancer risk: a
multipopulation pooled, cumulative exposure analysis. Diabetolo-
gia 2015;58:493504.
[59] Turner RM, Kwok CS, Chen-Turner C, Maduakor CA, Singh S, Loke
YK. Thiazolidinediones and associated risk of bladder cancer: A
systematic review and meta-analysis. Br J Clin Pharmacol 2014;
78:25873.
[60] Larre S, Catto JW, Cookson MS, et al. Screening for bladder cancer:
rationale, limitations, whom to target, and perspectives. Eur Urol
2013;63:104958.
[61] Kamat AM, Hegarty PK, Gee JR, et al. ICUD-EAU International
Consultation on Bladder Cancer 2012: Screening, diagnosis, and
molecular markers. Eur Urol 2013;63:415.
[62] Marcos-Gragera R, Mallone S, Kiemeney LA, et al. Urinary tract
cancer survival in Europe 19992007: Results of the population-
based study EUROCARE-5. Eur J Cancer 2015;51:221730.
[63] Leal J, Luengo-Fernandez R, Sullivan R, Witjes JA. Economic burden of
bladder cancer across the European Union. Eur Urol 2016;69:43847.
[64] Babjuk M, Burger M, Zigeuner R, et al. EAU guidelines on non-
muscle-invasive urothelial carcinoma of the bladder: Update 2013.
Eur Urol 2013;64:63953.
[65] Gakis G, Efstathiou J, Lerner SP, et al. ICUD-EAU International
Consultation on Bladder Cancer 2012: Radical cystectomy and
bladder preservation for muscle-invasive urothelial carcinoma of
the bladder. Eur Urol 2013;63:4557.
[66] Karim-Kos HE, de VE, Soerjomataram I, Lemmens V, Siesling S,
Coebergh JW. Recent trends of cancer in Europe: a combined
approach of incidence, survival and mortality for 17 cancer sites
since the 1990s. Eur J Cancer 2008;44:134589.
[67] Malmstrom PU. Why has the survival of patients with bladder
cancer not improved? BJU Int 2008;101:2679.
[68] Janssen F, Kunst AE. ICD coding changes and discontinuities in
trends in cause-specic mortality in six European countries, 1950-
99. Bull World Health Organ 2004;82:90413.
[69] Nielsen ME, Smith AB, Meyer AM, et al. Trends in stage-specic
incidence rates for urothelial carcinoma of the bladder in the
United States: 1988-2006. Cancer 2014;120:8695.
[70] Scottish Cancer Registry Web site. http://www.isdscotland.org/
Health-Topics/Cancer/Scottish-Cancer-Registry.asp.
[71] International rules for multiple primary cancers (ICD-0 ed. 3). Eur J
Cancer Prev 2005; 14:307-8.
[72] World Health Organisation. Global Status Report on Noncommu-
nicable Diseases. Geneva (Switzerland): WHO; 2014.
[73] Antoni S, Soerjomataram I, Moller B, Bray F, Ferlay J. An assessment
of GLOBOCAN methods for deriving national estimates of cancer
incidence. Bull World Health Organ 2016;94:17484.