E U RO P EAN U ROL OGY 78 (20 20 ) 89 3– 90 6

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Bladder Cancer

Global Trends of Bladder Cancer Incidence and Mortality, and

Their Associations with Tobacco Use and Gross Domestic Product
Per Capita

Jeremy Yuen-Chun Teoh a, Junjie Huang b, Wendy Yuet-Kiu Ko b, Veeleah Lok b, Peter Choi b,
Chi-Fai Ng a, Shomik Sengupta c, Hugh Mostafid d, Ashish M. Kamat e, Peter C. Black f,
Shahrokh Shariat g,h,i,j,k,l, Marek Babjuk g,j, Martin Chi-Sang Wong b,*
a
S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China; b JC School of Public Health and Primary Care,
Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China; c Eastern Health and Monash University Eastern Health Clinical School, Box
d
Hill, VIC, Australia; Department of Urology, Royal Surrey County Hospital, Guildford, Surrey, UK; e The University of Texas MD Anderson Cancer Center,
Houston, TX, USA; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada; g Department of Urology, Comprehensive Cancer
f

Center, Medical University of Vienna, Vienna, Austria; h Departments of Urology, Weill Cornell Medical College, New York, NY, USA; i Department of Urology,
University of Texas Southwestern, Dallas, TX, USA; j Department of Urology, Second Faculty of Medicine and Hospital Motol, Charles University, Prague, Czech
k
Republic; Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; l Division of Urology,
Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan

Article info Abstract

Article history: Background: Bladder cancer is a major urological disease, with approximately 550
Accepted September 3, 2020 000 new cases diagnosed in 2018.
Objective: We examined gender-specific incidence and mortality patterns, and trends of
Associate Editor: bladder cancer from a global perspective. We further investigated their associations with
Giacomo Novara tobacco use and gross domestic product (GDP) per capita.
Design, setting, and participants: We retrieved data on the incidence and mortality of
bladder cancer from the GLOBOCAN database, Cancer Incidence in Five Continents, and
Statistical Editor:
the WHO mortality database. Data on the rate of tobacco use were retrieved from the
Emily Zabor WHO Global Health Observatory. Data on GDP per capita was retrieved from the United
Nations Human Development Report.
Keywords: Outcome measurements and statistical analysis: We performed two sets of analyses. The
first set of analysis is based on bladder cancer incidence and mortality data in 2018. The
Bladder cancer
gender-specific age-standardised rates (ASRs) of incidence and mortality, and their corre-
Incidence lations with the rate of tobacco use and GDP per capita were investigated. A multivariable
Mortality linear regression analysis was also performed. In the second set of analysis, we examined
Smoking the 10-yr temporal trends of bladder cancer incidence and mortality by average annual
Tobacco percent change using joinpoint regression analysis. A further exploratory analysis on GDP
per capita in countries with decreasing trends of tobacco use was also performed.
Gross domestic product Results and limitations: Wide variations in bladder cancer incidence and mortality were
Epidemiology observed globally. There were positive correlations between the rate of tobacco use and
the ASRs of bladder cancer incidence (r = 0.20) and mortality (r = 0.38) in men, and
between the rate of tobacco use and the ASRs of bladder cancer incidence (r = 0.67) and
mortality (r = 0.22) in women. There were positive correlations between GDP per capita,

* Corresponding author. 4/F, School of Public Health and Primary Care, Prince of Wales Hospital,
Shatin, Hong Kong SAR, China. Tel. +852 2252 8782; Fax: +852 2606 3500.
E-mail address: wong_martin@cuhk.edu.hk (M.-S. Wong).

https://doi.org/10.1016/j.eururo.2020.09.006
0302-2838/© 2020 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
894 EU ROP E AN U RO LO GY 7 8 (2 02 0) 8 93 –9 0 6

and the ASRs of bladder cancer incidence in men (r = 0.48) and women (r = 0.44). There
was a weak positive correlation between GDP per capita and bladder cancer mortality in
men (r = 0.19), but no correlation with bladder cancer mortality in women (r = 0.06).
Upon multivariable linear regression analysis, tobacco use was significantly associated
with bladder cancer incidence and mortality in men, and bladder cancer incidence in
Please visit women. Regarding the 10-yr temporal trends of bladder cancer, Europe has an increasing
www.eu-acme.org/europeanurology to answer incidence but decreasing mortality, and Asia has a decreasing incidence but increasing
questions on-line. The EU-ACME credits will male mortality. Among countries with decreasing trends of tobacco use, the mean GDP
then be attributed automatically. per capita was higher in countries with decreasing trends of bladder cancer mortality
than in those with increasing trends of bladder cancer mortality. A major limitation of
the study is that cancer incidence might be underdetected and under-reported in less
developed nations.
Conclusions: There were observable trends of bladder cancer incidence and mortality
globally. Tobacco use was significantly associated with both bladder cancer incidence
and mortality. A certain level of economic capacity might be needed to further reduce
bladder cancer mortality in countries with a decreasing trend of tobacco use.
Patient summary: There are different trends of bladder cancer incidence and mortality
globally. Smoking is significantly associated with the incidence and mortality of bladder
cancer. A higher financial capacity may be needed to further improve the disease outcomes.
© 2020 The Author(s). Published by Elsevier B.V. on behalf of European Association of
Urology. This is an open access article under the CC BY-NC-ND license (http://creati-
vecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction 2. Patients and methods

Bladder cancer is the 11th most common cancer world- We performed two sets of analyses in this study. The first set of analysis
wide, with approximately 550 000 new cases being was based on bladder cancer incidence and mortality data in 2018. The
diagnosed every year [1]. Tobacco contains a rich source second set of analysis was based on the 10-yr temporal trends of bladder
of carcinogenic compounds, and it is the most important cancer incidence and mortality.
risk factor for bladder cancer, with an attributable risk of
about 50% [2]. Tobacco use may also affect the progression 2.1. Source of data
of bladder cancer and has important implications on
bladder cancer mortality [2,3]. Early access and adequate 2.1.1. Analysis based on bladder cancer incidence and mortality data
provision of health care services are crucial for early in 2018
Data on bladder cancer incidence and mortality pattern were retrieved
bladder cancer detection and better oncological control in
from the GLOBOCAN database (2018) [1]. Gender-specific age-standar-
the long run. To a large extent, this depends on the
dised rate (ASR) per 100 000 was used for both incidence and mortality
financial capacity of the affected individual and the nature
figures. We also used the GLOBOCAN data to examine the correlations
of health care system of the country in which he/she with tobacco use and GDP per capita. Data on the rates of tobacco use in
resides. 2010 in each country were retrieved from the WHO Global Health
Previously, Antoni et al. [4] conducted a review on the Observatory [8]. Data on GDP per capita in 2018 for each country was
incidence and mortality trend of bladder cancer using retrieved from the United Nations Human Development Report [9].
figures from the GLOBOCAN database (2012), Cancer
Incidence in Five Continents (up to 2007), and the WHO 2.1.2. Ten-year time trend analysis on bladder cancer incidence and
mortality database (up to 2012). Cumberbatch et al. [5] mortality
further published a comprehensive systematic review on A time trend analysis on bladder cancer incidence and mortality was
the epidemiology and risk factors of bladder cancer. In performed using the incidence/mortality figures of the past 10 yr from the
recent years, the gender-specific figures on the global Cancer Incidence in Five Continents (up to 2012) and the WHO mortality
database (up to 2016). These databases captured the incidence and mortality
incidence and mortality of bladder cancer have been
data in approximately 65 and 140 countries or regions, respectively.
updated [1,6,7].
We also performed an exploratory analysis on GDP per capita in
In this article, we investigated the associations of tobacco
countries with decreasing trends of tobacco use. The trends of tobacco use in
use and gross domestic product (GDP) per capita, with each country were determined using data from the WHO Global Health
bladder cancer incidence and mortality. Tobacco use is a Observatory (2000 and 2010) [8]. GDP per capita in 2018 for each country
major risk factor of bladder cancer, and GDP per capita is an was retrieved from the United Nations Human Development Report [9].
index reflecting a country's economic capacity to manage
bladder cancer. Bladder cancer incidence and mortality data 2.2. Data synthesis and statistical analysis
in 2018, as well as the temporal trends in the last available
10 yr were used as the outcomes of interest. We believe that 2.2.1. Analysis based on bladder cancer incidence and mortality
the results may provide valuable insight into how we can data in 2018
manage bladder cancer from a public health and global We first generated the heat maps on age-standardised incidence and
perspective. mortality rates from the WHO website to provide our readers an overall
 E URO PE AN U ROLO GY 7 8 ( 202 0) 8 93 – 90 6 895

picture of bladder cancer incidence and mortality globally [10]. The 2.2.2. Ten-year time trend analysis on bladder cancer incidence and
overall correlations between the ASRs of bladder cancer incidence mortality
and mortality, and tobacco use and the GDP per capita, stratified by Temporal trends of bladder cancer incidence and mortality were plotted.
sex, were examined using Pearson correlation coefficients (r). A A joinpoint regression analysis was used to analyse the incidence and
multivariable linear regression analysis was performed to investigate mortality trends and to identify the time point at which the trend
whether tobacco use and GDP per capita were significant factors significantly changes [11]. Logarithmic transformation of age-standar-
associated with bladder cancer incidence and mortality. Interactions dised incidence and mortality rates was performed, and standard errors
between tobacco use and GDP per capita were also tested in the were computed using binomial approximation. A maximum of three
regression analysis. joinpoints were used as analysis options, and the average annual percent

Fig. 1 – Estimated age-standardised incidence rates for (A) men and (B) women in 2018. ASR = age-standardised rate.
896 EU ROP E AN U RO LO GY 7 8 (2 02 0) 8 93 –9 0 6

change (AAPC) was estimated. The AAPC was computed as a We further performed an exploratory analysis in countries with
geometrically weighted average, with the weights being equivalent to decreasing trends of tobacco use. Countries with a lower rate of
the length of each segment within the specified time interval [12]. AAPCs tobacco use in 2010 than those in 2000 were considered to have a
with a 95% confidence interval (CI) of > 0 was considered a significantly decreasing trend of tobacco use. We divided the countries with a
increasing trend. Likewise, AAPCs with a 95% CI of < 0 was considered a decreasing trend of tobacco use into two groups: group 1 included
significant decreasing trend [13–15]. This methodology has widely been countries with decreasing bladder cancer incidence/mortality and
used to examine the incidence and mortality trends of various types of group 2 included countries with increasing bladder cancer inci-
cancers [4,5,13,16–20]. dence/mortality. The mean GDP per capita between the two groups

Fig. 2 – Estimated age-standardised mortality rates for (A) men and (B) women in 2018. ASR = age-standardised rate.
 E URO PE AN U ROLO GY 7 8 ( 202 0) 8 93 – 90 6 897

was compared using the Mann-Whitney U test. A p value of <0.05 The heat maps for the ASRs of bladder cancer incidence
was considered statistically significant. and mortality are shown in Figures 1 and 2, respectively.
The detailed figures are summarised in the Supplementary
3. Results material.

3.1. Analysis based on bladder cancer incidence and mortality 3.1.2. Correlations between the incidence/mortality of bladder
data in 2018 cancer and tobacco use in men and women
For men, there were positive correlations between tobacco
3.1.1. Age-standardised incidence and mortality rates of bladder use and bladder cancer incidence (r = 0.20) and between
cancer in 2018 tobacco use and mortality (r = 0.38). For women, there was a
There were a total of 549 393 new cases of bladder cancer strong positive correlation between tobacco use and
and 199 922 cases of bladder cancer–related deaths in bladder cancer incidence (r = 0.67), and a weak positive
2018. For the male population, a wide variation was correlation between tobacco use and bladder cancer
observed in the ASRs of bladder cancer incidence, ranging mortality (r = 0.22; Fig. 3).
from 1.3 per 100 000 in middle Africa to 26.5 per 100
000 in Southern Europe; for the female population, the 3.1.3. Correlations between the incidence/mortality of bladder
variation of ASRs in bladder cancer incidence was less cancer and GDP per capita in men and women
prominent, ranging from 0.8 per 100 000 in South Central There were moderate positive correlations between GDP
Asia to 5.5 per 100 000 in Southern Europe. The ASRs of per capita and bladder cancer incidence in men (r = 0.48)
bladder cancer mortality were 3.2 per 100 000 for the male and women (r = 0.44). There was a weak positive
population and 0.9 per 100 000 for the female population. correlation between GDP per capita and bladder cancer

Fig. 3 – Correlations between the rate of tobacco use and (A) bladder cancer incidence in men, (B) bladder cancer mortality in men, (C) bladder cancer
incidence in women, and (D) bladder cancer mortality in women. 95% CI = 95% confidence interval.
898 EU ROP E AN U RO LO GY 7 8 (2 02 0) 8 93 –9 0 6

Fig. 4 – Correlations between GDP per capita and (A) bladder cancer incidence in men, (B) bladder cancer mortality in men, (C) bladder cancer
incidence in women, and (D) bladder cancer mortality in women. 95% CI = 95% confidence interval; GDP = gross domestic product.

mortality in men (r = 0.19), but no correlation between 3.2. Ten-year time trend analysis on bladder cancer incidence
GDP per capita and bladder cancer mortality in women and mortality
(r = 0.06; Fig. 4).
3.2.1. Incidence and mortality trends of bladder cancer from a global
3.1.4. Multivariable linear regression analysis on bladder cancer perspective
incidence and mortality Among men, there were decreasing trends of bladder cancer
Upon multivariable linear regression analysis (Table 1), incidence in countries from Asia, Oceania, North America,
tobacco use was a significant factor associated with and South America (Fig. 5). On the contrary, there was an
bladder cancer incidence in men (coefficient 0.152, 95% increasing trend of bladder cancer incidence in European
CI 0.017–0.286, p = 0.027) and women (coefficient 0.116, countries. Of note, among the five countries with significant
95% CI 0.078–0.154, p < 0.001). Tobacco use was associated increases in bladder cancer incidence worldwide, four were
with bladder cancer mortality in men (coefficient 0.067, European countries. Among females, there were also
95% CI 0.025–0.108, p = 0.002), but not associated with decreasing trends of bladder cancer incidence in countries
bladder cancer mortality in women (coefficient 0.015, 95% from Asia, Oceania, North America, and South America
CI–0.003 to 0.033, p = 0.095). GDP per capita was not (Fig. 6). In contrast, there were increasing trends of bladder
associated with bladder cancer incidence and mortality in cancer incidence in women in European countries. There
both men and women. No significant interactions between were a total of 10 countries with significant increases in
tobacco use and GDP per capita were noted in all bladder cancer in women worldwide, and nine of them were
regression analyses. from Europe.
 E URO PE AN U ROLO GY 7 8 ( 202 0) 8 93 – 90 6 899

Table 1 – Multivariable linear regression analysis on bladder cancer incidence and mortality in men and women

Coefficient 95% CI p value

Lower Upper

Male bladder cancer incidence

Tobacco use 0.152 0.017 0.286 0.027
GDP per capita 0.001 0.001 0.001 1.0
Tobacco use  GDP per capita 0.001 0.001 0.001 0.064
Male bladder cancer mortality
Tobacco use 0.067 0.025 0.108 0.002
GDP per capita 0.001 0.001 0.001 0.5
Tobacco use  GDP per capita 0.001 0.001 0.001 0.14
Female bladder cancer incidence
Tobacco use 0.116 0.078 0.154 <0.001
GDP per capita 0.001 0.001 0.001 0.5
Tobacco use  GDP per capita 0.001 0.001 0.001 0.9
Female bladder cancer mortality
Tobacco use 0.015 0.003 0.033 0.095
GDP per capita 0.001 0.001 0.001 0.3
Tobacco use  GDP per capita 0.001 0.001 0.001 0.5

CI = confidence interval; GDP = gross domestic product.

In the male population, there were decreasing trends of 4. Discussion

bladder cancer mortality in countries from Oceania, North
America, and Europe (Fig. 7). Among the 18 countries with In this study, we provided a comprehensive update on the
significant decreases in bladder cancer mortality, 12 were patterns and temporal trends of bladder cancer incidence
from Europe. On the contrary, there were three countries and mortality, and we also explored their associations with
with significant increases in bladder cancer mortality, and tobacco use and GDP per capita. The results provided
two of them were from Asia. In the female population, there valuable insight into understanding the epidemiology of
were decreasing trends of bladder cancer mortality in bladder cancer and how we can improve the situation from
countries from North America and Europe (Fig. 8). There a wider perspective.
were a total of nine countries with significant decreases in
bladder cancer mortality, and six of them were from Europe. 4.1. Tobacco use, gender, and bladder cancer incidence/
Among the four countries with significant increases in mortality
bladder cancer mortality, two were from Asia and two were
from Europe. Tobacco is a rich source of carcinogenic compounds
Temporal trends and joinpoint regression graphs of including polycyclic aromatic hydrocarbons, aromatic
incidence and mortality for each individual country are amines, heterocyclic amines, and N-nitroso compounds
presented in the Supplementary material. For the joinpoint [21]. Smoking is a significant factor associated with
regression analysis, the time point at which there was a bladder cancer, and its harm tends to increase with
change in the incidence/mortality trend for each individual smoking intensity and smoking duration [3]. Smoking
country was also illustrated. might also affect the progression of bladder cancer, as
reflected by the highest disease-specific mortality among
3.2.2. GDP per capita in countries with decreasing trends of tobacco current smokers [2].
use According to the GLOBOCAN data in 2018 [1], the ASRs
In this analysis, we focused on countries with decreasing of bladder cancer incidence were 9.6 per 100 000 for
trends of tobacco use and determined whether the GDP per males and 2.4 per 100 000 for females, corresponding to a
capita differed between countries with decreasing trends of male to female ratio of 4:1. Similarly, the risk of bladder
bladder cancer incidence/mortality (group 1) and countries cancer mortality was also 3.6 times higher in the male
with increasing trends of bladder cancer incidence/mortal- population (ASRs of 3.2 per 100 000 for males and 0.9 per
ity (group 2; Table 2). In terms of male and female bladder 100 000 for females). It is important to take note that
cancer incidence, there were no significant differences in these results were global figures without adjustment of
GDP per capita between the two groups. For male bladder tumour stage, tumour grading, and treatment modality.
cancer mortality, group 1 had a significantly higher GDP Gender disparity in the development and progression of
capita than group 2 (USD: 42 184  4133 vs 22 112  5317, bladder cancer is possible due to potential biological and
p = 0.003). For female bladder cancer mortality, group 1 also hormonal differences [22–26]. To complicate it further,
had a significantly higher GDP capita than group 2 (USD: 48 delays in presentation and diagnostic workup in female
000  4176 vs 23 197  4859, p < 0.001). patients have been reported previously [27–29]; this may
900 EU ROP E AN U RO LO GY 7 8 (2 02 0) 8 93 –9 0 6

Male Incidence (0–85 years old)

Oceania New Zealand -10.00*(-13.73 to -6.11), p< 0.001
Australia -0.42 (-0.97 to 0.12), p=0.11

Asia Hong Kong, SAR, China -8.86*(-13.19 to -4.31), p< 0.001

Philippines -3.92 (-7.80 to 0.13), p=0.06
China -3.88*(-5.93 to -1.79), p< 0.001
India -1.84 (-5.50 to 1.95), p=0.3
Korea -1.67*(-2.40 to -0.93), p=0.001
Bahrain -1.61 (-7.90 to 5.11), p=0.6
Israel -1.48*(-2.64 to -0.31), p=0.020
Thailand 0.92 (-1.11 to 2.98), p=0.3
Kuwait 4.07 (-1.94 to 10.44), p=0.16
Japan 4.79*(3.18 to 6.42), p< 0.001

Africa Uganda 2.82 (-23.18 to 37.62), p=0.8

Northern USA -0.98*(-1.58 to -0.38), p=0.006

America Canada -0.18 (-0.99 to 0.63), p=0.6

Latin America & the Chile -11.33 (-24.57 to 4.23), p=0.15

Caribbean Brazil -2.80 (-6.58 to 1.13), p=0.14
Colombia -1.45 (-6.10 to 3.43), p=0.5
Costa Rica -0.30 (-1.47 to 0.88), p=0.6
Ecuador 1.30 (-3.45 to 6.29), p=0.6

Northern Faroe Islands -8.58 (-18.90 to 3.06), p=0.12

Europe United Kingdom -1.23*(-1.75 to -0.70), p=0.001
Lithuania -0.15 (-1.60 to 1.32), p=0.8
Denmark 0.00 (-0.73 to 0.74), p=1
Finland 0.01 (-0.75 to 0.77), p=1
Iceland 0.12 (-2.53 to 2.83), p=1
Sweden 0.12 (-0.82 to 1.08), p=0.8
Norway 0.46 (-0.99 to 1.93), p=0.5
Estonia 0.70 (-1.09 to 2.53), p=0.4
Ireland 1.34*(0.30 to 2.39), p=0.018
Greenland 9.43 (-9.26 to 31.98), p=0.3

Western Austria -3.36*(-4.76 to -1.94), p=0.001

Europe France -0.31 (-1.20 to 0.58), p=0.4
Netherlands 0.26 (-0.16 to 0.68), p=0.19
Belarus 0.87 (-0.19 to 1.94), p=0.10
Germany 1.27 (-0.27 to 2.83), p=0.10
Switzerland 3.31*(2.09 to 4.54), p< 0.001

Southern Europe Cyprus -1.04 (-3.58 to 1.56), p=0.4

Italy -0.29 (-0.96 to 0.38), p=0.3
Slovenia -0.22 (-1.82 to 1.40), p=0.8
Malta 0.07 (-2.76 to 2.99), p=1
Spain 0.56 (-0.01 to 1.14), p=0.053
Turkey 0.95 (-1.13 to 3.07), p=0.4
Croatia 2.5*(0.56 to 4.48), p=0.018
Bulgaria 2.63*(1.32 to 3.95), p=0.002

Eastern Europe Czech Republic -0.32 (-0.80 to 0.17), p=0.17

Poland 0.92 (-1.46 to 3.35), p=0.4
Slovakia 2.31*(1.29 to 3.34), p=0.001

-15 -12 -9 -6 -3 0 3 6 9

Fig. 5 – The average annual percent change in the incidence of bladder cancer in men. *p < 0.05.

result in a more advanced disease upon presentation and hopefully the global incidence and mortality of bladder
poorer long-term survival. cancer can be improved in the long run.
Our results showed positive correlations between
tobacco use, and bladder cancer incidence and mortality, 4.2. GDP per capita and bladder cancer incidence/mortality
in both men and women. Upon multivariable linear
regression analysis, tobacco use was significantly associated GDP represents the total monetary value of all final goods
with bladder cancer incidence and mortality in men, and and services produced within a country, and it is often used
bladder cancer incidence in women. Although tobacco use as an indicator of economic well-being. The financial
was not significantly associated with bladder cancer capacity of an individual and the economic capacity of
mortality in women, the potential harm of smoking may his/her country may have strong implications on his/her
be underestimated given the generally low rates of tobacco access to diagnostic and therapeutic health care services
use in women. The WHO has set a global target of a 30% [31–33]. Our results showed that a higher GDP per capita
relative reduction in the prevalence of tobacco use in was positively correlated with the ASR of bladder cancer
persons aged 15 yr by 2025 [30]. With such an initiative, incidence. This can be a result of better awareness of the
 E URO PE AN U ROLO GY 7 8 ( 202 0) 8 93 – 90 6 901

Female Incidence (0-85 years old)

Oceania New Zealand -6.52*(-12.54 to -0.09), p=0.048

Australia -0.64 (-1.73 to 0.46), p=0.214

Asia Hong Kong, SAR, China -7.70*(-11.39 to -3.86), p< 0.001

Philippines -4.59 (-10.94 to 2.20), p=0.180
China -4.39*(-5.94 to -2.82), p< 0.001
Thailand -3.65 (-7.43 to 0.29), p=0.065
Kuwait -2.82 (-10.91 to 6.01), p=0.470
Korea -2.19*(-3.48 to -0.89), p=0.005
Israel -0.90 (-4.61 to 2.95), p=0.642
India -0.41 (-5.48 to 4.93), p=0.860
Bahrain
0.93 (-17.21 to 23.03), p=0.917
Japan 5.13*(3.02 to 7.28), p< 0.001

-1.57 (-13.18 to 11.59), p=0.778

Africa Uganda

Northern USA -1.21*(-1.91 to -0.51), p=0.004

America Canada -0.72*(-1.35 to -0.10), p=0.029

Latin America & the Colombia -5.07*(-8.68 to -1.31), p=0.015

Caribbean Brazil -4.21 (-9.52 to 1.41), p=0.120
Costa Rica -1.77 (-6.81 to 3.55), p=0.458
2.00 (-11.92 to 18.11), p=0.792
Chile
Ecuador 2.09 (-5.42 to 10.19), p=0.550

Northern Iceland -4.83*(-9.07 to -0.40), p=0.036

Europe United Kingdom -0.74*(-1.43 to -0.05), p=0.039
Denmark -0.50*(-0.97 to -0.04), p=0.037
Lithuania -0.30 (-2.32 to 1.76), p=0.743
Ireland 0.25 (-1.35 to 1.87), p=0.733
Finland 0.32 (-0.91 to 1.55), p=0.570
Sweden 1.20 (-0.16 to 2.57), p=0.083
Norway 2.47*(1.35 to 3.6), p=0.001
Estonia 2.89*(0.02 to 5.85), p=0.049
Faroe Islands
3.82 (-13.77 to 25.01), p=0.654

Western Austria -2.07*(-3.33 to -0.79), p=0.006

Europe France 1.62 (-0.78 to 4.07), p=0.159
Germany 1.99*(0.60 to 3.40), p=0.011
Belarus 2.11*(0.05 to 4.20), p=0.045
Netherlands 2.29*(1.01 to 3.59), p< 0.001
Switzerland 2.93 (-0.46 to 6.43), p=0.082

Southern Europe Malta -1.58 (-6.51 to 3.61), p=0.496

Italy -0.13 (-2.76 to 2.56), p=0.910
Slovenia 0.71 (-1.99 to 3.48), p=0.565
Cyprus 1.41 (-3.37 to 6.42), p=0.522
Turkey 2.19 (-0.08 to 4.52), p=0.057
Croatia 3.01*(1.05 to 5.01), p=0.007
Spain 3.81*(2.52 to 5.11), p< 0.001
Bulgaria 4.19*(2.97 to 5.41), p< 0.001

Eastern Czech Republic -0.80 (-1.72 to 0.12), p=0.080

Europe Poland 3.05 (-1.47 to 7.78), p=0.161

Slovakia 4.93*(1.84 to 8.12), p=0.006

-15 -12 -9 -6 -3 0 3 6 9 12

Fig. 6 – The average annual percent change in the incidence of bladder cancer in women. *p < 0.05.

disease and easier access to the health care system, bladder cancer in the past two decades [35,36]. On the
resulting in earlier detection of bladder cancer in wealthier contrary, when we focus on countries with decreasing
countries. Another postulation is that countries with higher trends of tobacco use, countries with decreasing trends of
GDP may have differences in dietary habits such as bladder cancer mortality had a higher mean GDP per capita
increased meat consumption [34]. Dietary factors were than those with increasing trends of bladder cancer
suspected risk factors of bladder cancer [5], but the link was mortality. Therefore, a certain degree of economic capacity
not well established. While we expect a better health care may still be important to further reduce the mortality rates
delivery for advanced bladder cancer in wealthier countries, in countries with decreasing trends of tobacco use.
we detected only a weak positive correlation between GDP
per capita and the ASR of bladder cancer mortality in men, 4.3. Incidence and mortality trends of bladder cancer
and no correlation in women. GDP per capita was also not
associated with bladder cancer mortality upon multivari- We observed relatively consistent patterns of bladder
able linear regression analysis. This may be a reflection of a incidence and mortality across countries within the same
relative lag in advancement in the treatment of advanced continent, in particular for Europe, North America, Oceania,
902 EU ROP E AN U RO LO GY 7 8 (2 02 0) 8 93 –9 0 6

Fig. 7 – The average annual percent change in the mortality of bladder cancer in men. *p < 0.05.

and Asia. Apart from the rates of tobacco use and GDP per and Asia, in both incidence and mortality trends of bladder
capita, the existing health care policy and the mode of cancer. The possible underlying reasons for such differences
health care delivery may also have a significant impact on are discussed in the following sections.
the incidence and mortality trends of bladder cancer. The
establishment of bladder cancer advocacy groups may also 4.3.1. Europe—increase in incidence but decrease in mortality
affect the public's awareness towards this disease. Interest- We observed an increase in incidence but a decrease in
ingly, we observed contrasting differences between Europe mortality for bladder cancer in European countries. This
 E URO PE AN U ROLO GY 7 8 ( 202 0) 8 93 – 90 6 903

Female Mortality (0-85 years old)

Oceania Australia -2.60*(-4.16 to -1.02), p=0.005

New Zealand 0.54 (-3.72 to 5.00), p=0.780

Asia Singapore -5.56 (-14.77 to 4.63), p=0.234

Hong Kong, SAR, China -3.12 (-7.49 to 1.45), p=0.151
Kuwait -2.29 (-15.83 to 13.43), p=0.730

Korea -0.83 (-1.84 to 0.20), p=0.099

Japan 0.51*(0.00 to 1.03), p=0.050
Israel 0.68 (-1.64 to 3.06), p=0.519
Philippines 2.32 (-1.49 to 6.27), p=0.201
Thailand 5.13*(3.27 to 7.02), p< 0.001

Northern Canada -1.29*(-2.36 to -0.21), p=0.025

America USA -0.77*(-1.15 to -0.38), p=0.002

Latin America & Colombia -1.57 (-4.39 to 1.34), p=0.245

the Caribbean Brazil 0.56 (-0.07 to 1.20), p=0.073
Chile 1.13 (-2.68 to 5.10), p=0.518
Costa Rica 2.51 (-6.44 to 12.32), p=0.549
Ecuador 2.91 (-1.55 to 7.56), p=0.174

Northern Denmark -3.66*(-5.28 to -2.01), p=0.001

Europe Norway -3.45 (-7.15 to 0.41), p=0.073
United Kingdom -0.51*(-0.96 to -0.06), p=0.030
Finland -0.22 (-3.22 to 2.87), p=0.870

Ireland -0.17 (-4.17 to 3.99), p=0.925

Sweden 0.59 (-2.15 to 3.40), p=0.637
Lithuania 0.67 (-2.38 to 3.82), p=0.629
Latvia 1.74 (-4.02 to 7.84), p=0.515
Estonia 2.01 (-2.66 to 6.90), p=0.356
Iceland 2.31 (-14.63 to 22.62), p=0.778

Southern Europe Malta -6.01 (-21.24 to 12.17), p=0.442

Spain -1.13 (-2.36 to 0.12), p=0.070

Italy -0.47 (-1.06 to 0.12), p=0.101
Slovenia -0.46 (-5.31 to 4.65), p=0.839
Bulgaria 0.31 (-2.56 to 3.26), p=0.814
Portugal 1.03 (-0.47 to 2.55), p=0.153
Croatia 3.23*(1.18 to 5.32), p=0.006
Cyprus 4.08 (-8.30 to 18.12), p=0.487

Western Netherlands -1.95*(-3.57 to -0.31), p=0.026

Europe Germany -1.70*(-2.36 to -1.03), p< 0.001
Austria -1.68 (-4.18 to 0.89), p=0.169
France -1.47*(-2.32 to -0.62), p=0.004
Belgium -1.35 (-3.10 to 0.44), p=0.120
Switzerland -0.80 (-2.74 to 1.19), p=0.379

Eastern Europe Russian Federation -1.63*(-2.32 to -0.93), p=0.001

Czech Republic -1.13 (-2.89 to 0.65), p=0.179
Slovakia 1.09 (-0.87 to 3.09), p=0.238
Poland 1.55*(0.75 to 2.36), p=0.002

-15 -12 -9 -6 -3 0 3 6 9 12 15

Fig. 8 – The average annual percent change in the mortality of bladder cancer in women. *p < 0.05.

may be due to better awareness and earlier detection of the any of the 27 European Union countries under the same
disease, resulting in better oncological control and reduc- conditions and at the same cost as people insured in that
tion in mortality. Universal health coverage (UHC) is country [39]. The UHC partnership initiative is still
important to ensure access to urological care without relatively young; it will be interesting to see whether the
suffering financial hardship [37]. The UHC partnership increasing incidence of bladder cancer will reach a turning
initiative has been established since 2011, and most point as the programme matures with time. There are also
European countries were involved in this initiative [38]. Eu- an increasing number of patient advocacy groups for the
ropean Health Insurance Card also allows an individual betterment of patients suffering from bladder cancer. For
access to medically necessary, state-provided health care in example, Fight Bladder Cancer is a UK-based bladder cancer
904 EU ROP E AN U RO LO GY 7 8 (2 02 0) 8 93 –9 0 6

Table 2 – Mean GDP per capita among countries with a decreasing trend of tobacco use

Group 1a Group 2b p value

Male bladder cancer incidence n = 19 n = 21

GDP per capita (USD) 28 403  4386 34 934  5983 0.6
Male bladder cancer mortality n = 26 n = 14
GDP per capita (USD) 42 184  4133 22 112  5317 0.003
Female bladder cancer incidence n = 20 n = 19
GDP per capita (USD) 30 476  5221 36 376  5844 0.5
Female bladder cancer mortality n = 22 n = 16
GDP per capita (USD) 48 000  4176 23 197  4859 <0.001

GDP = gross domestic product.

a
Group 1: countries with a decreasing trend of bladder cancer incidence/mortality.
b
Group 2: countries with an increasing trend of bladder cancer incidence/mortality.

charity founded and run by bladder cancer survivors and developed nations. Likewise, cancer registries that
their families [40]. Better awareness of the disease certainly include reported figures from a small region of the
plays an important role in early detection and treatment of country may limit the generalisability and representation
bladder cancer. of the findings. Second, we examined the correlations
between tobacco use and bladder cancer incidence/
4.3.2. Asia—decrease in incidence but increase in male mortality mortality. However, correlation does not imply causation,
A decrease in bladder cancer incidence in Asia appears to be and we must pay extra caution while interpreting the
promising, but at the same time worrying when it is magnitude of the correlation coefficients. Country-level
accompanied by an increase in male mortality. Most Asian data were used for our regression analysis, but it does not
countries are considered economically developing coun- allow more granular analysis based on individuals. The
tries [41]. The public hospital sector is often underdevel- present analysis did not incorporate the tissue type,
oped and may not be able to meet community needs due to staging, and other characteristics of bladder cancer. These
the lack of financial and policy support [42]. Limited access disease characteristics certainly have important implica-
to health care services may lead to underdetection of tions on the mortality rate, but are impossible to adjust
bladder cancer, resulting in late presentation of the disease. based on the available global data. Third, rates of tobacco
Lack of access to more advanced oncological treatment may use in 2010 were used as we expected a lead time
also affect long-term cancer control. All these factors may between tobacco use and the development of bladder
lead to higher bladder cancer mortality in the long run. The cancer [3]. However, they do not reflect on the exact
problem of an ageing population also appears to be much duration and intensity of tobacco use. This may induce a
more severe in Asia than in the other continents [43]. Blad- bias to the analysis and interpretation of the results. It is
der cancer affects elderly men with a median diagnosis age also difficult to obtain global data on the other risk factors
of 73 yr [5], and it is likely to be an increasing problem in of bladder cancer, such as occupational carcinogenic
Asian countries where population growth continues more exposure and schistosomiasis; therefore, these factors
than in other areas of the world. There is an urgent need for were not taken into account in our study. Fourth, different
additional resource allocation in the health care sector. cancer registries might have different guidelines on how
Reform of the health care systems in Asia has also been to document a cancer case or cancer death, and this policy
proposed [42]. could change over time. Disease coding practices may
differ among the countries, and this might affect the
4.4. Strengths and limitations changes in temporal trends. Nevertheless, we believe that
this study provides valuable insight into the most
This study provides an updated overview of the global updated global trends and patterns of bladder cancer,
incidence and mortality of bladder cancer as well as their and have important implications on health care policy
temporal trends. The data extracted from the GLOBOCAN making and how we can improve bladder cancer
database, Cancer Incidence in Five Continents, and the incidence and mortality from a wider perspective.
WHO mortality database are of high quality in terms of
their validity and completeness, especially when the 5. Conclusions
International Agency for Research on Cancer continues to
take active steps to refine the estimation methods for We observed different trends of bladder cancer incidence
better data quality and availability [44]. Nevertheless, and mortality globally. Tobacco use was significantly
there are several limitations that should be addressed. associated with both bladder cancer incidence and mortali-
First, although data from GLOBOCAN and Cancer Inci- ty. Hence, a global effort to promote smoking cessation is
dence in Five Continents were all derived from country- extremely important to reduce bladder cancer incidence
specific cancer registries, cancer incidence might be and mortality in the long run. Among countries with a
underdetected and under-reported, especially in less decreasing trend of tobacco use, a certain level of economic
 E URO PE AN U ROLO GY 7 8 ( 202 0) 8 93 – 90 6 905

capacity might be needed to reduce bladder cancer [9] United Nations Development Programme. Human development
mortality further. reports 2018 statistical update. http://hdr.undp.org/en/content/
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[10] World Health Organization. Global Cancer Observatory. https://gco.
Author contributions: Martin Chi-Sang Wong had full access
iarc.fr/today/online-analysis-map.
to all the data in the study and takes responsibility for the
[11] Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for
integrity of the data and the accuracy of the data analysis.
joinpoint regression with applications to cancer rates. Stat Med
2000;19:335–51.
Study concept and design: Teoh, Wong.
[12] Clegg LX, Hankey BF, Tiwari R, Feuer EJ, Edwards BK. Estimating
Acquisition of data: Huang, Ko, Lok, Choi.
average annual per cent change in trend analysis. Stat Med
Analysis and interpretation of data: Teoh, Huang, Choi.
2009;28:3670–82.
Drafting of the manuscript: Teoh, Wong.
[13] Wong MC, Goggins WB, Wang HH, et al. Global incidence and
Critical revision of the manuscript for important intellectual content: Ng,
mortality for prostate cancer: analysis of temporal patterns and
Sengupta, Mostafid, Kamat, Black, Shariat, Babjuk.
trends in 36 countries. Eur Urol 2016;70:862–74.
Statistical analysis: Huang, Ko, Lok, Choi.
[14] Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray
Obtaining funding: None.
F. Global patterns and trends in colorectal cancer incidence and
Administrative, technical, or material support: None.
mortality. Gut 2017;66:683–91.
Supervision: Ng, Wong.
[15] DeSantis CE, Bray F, Ferlay J, Lortet-Tieulent J, Anderson BO, Jemal A.
Other: None.
International variation in female breast cancer incidence and mor-
tality rates. Cancer Epidemiol Biomarkers Prev 2015;24:1495–506.
Financial disclosures: Martin Chi-Sang Wong certifies that all conflicts of
[16] Wong MCS, Huang JLW, George J, et al. The changing epidemiology
interest, including specific financial interests and relationships and
of liver diseases in the Asia-Pacific region. Nat Rev Gastroenterol
affiliations relevant to the subject matter or materials discussed in the
Hepatol 2019;16:57–73.
manuscript (eg, employment/affiliation, grants or funding, consultan-
[17] Wong MCS, Hamilton W, Whiteman DC, et al. Global incidence and
cies, honoraria, stock ownership or options, expert testimony, royalties,
mortality of oesophageal cancer and their correlation with socio-
or patents filed, received, or pending), are the following: None.
economic indicators temporal patterns and trends in 41 countries.
Sci Rep 2018;8:4522.
Funding/Support and role of the sponsor: None.
[18] Wong MCS, Lao XQ, Ho KF, Goggins WB, Tse SLA. Incidence and
mortality of lung cancer: global trends and association with socio-
economic status. Sci Rep 2017;7:14300.
[19] Znaor A, Lortet-Tieulent J, Laversanne M, Jemal A, Bray F. Interna-
Appendix A. Supplementary data tional variations and trends in renal cell carcinoma incidence and
mortality. Eur Urol 2015;67:519–30.
Supplementary material related to this article can be [20] Znaor A, Lortet-Tieulent J, Jemal A, Bray F. International variations
found, in the online version, at https://doi.org/10.1016/j. and trends in testicular cancer incidence and mortality. Eur Urol
eururo.2020.09.006. 2014;65:1095–106.
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