3.1 Overview of current global urologic cancer epidemiology
The data of 174 countries available both in the 2018 GLOBOCAN database and 2018 HDI statistics were incorporated. Development levels of countries were classified into 4 classes according to HDI values by the UNDP (Fig. 1a). The global age-standardized incidence and mortality rates of prostate, bladder and kidney cancer in 2018 were presented separately (Fig. S1a-f). Mortality-to-incidence ratios (MIRs) were calculated for prostate, bladder and kidney cancer and their global distribution was depicted in the form of world maps (Fig. 1b-d). It is estimated that there will be almost 1.8 million new cases of urologic cancer and 616,000 associated deaths worldwide in 2018, showing slightly decreasing tendency compared with 2012 (2.2 million new cases and 734,000 deaths). The global MIR of urologic cancer was 0.282 in 2018 and 0.286 in 2012, with almost no fluctuation.
Prostate cancer had a cumulative 1.3 million new cases and 359,000 deaths worldwide in 2018, ranking as the second most frequent cancer in men. The top countries with the highest incidence rates of prostate cancer were all in very-high HDI group (Fig. S1a), including Europe (e.g., Ireland, Estonia, Norway, Sweden, France, United Kingdom, Czech Republic, Latvia, Slovenia, Luxembourg, Switzerland, Denmark), North America (United States), Australia/ New Zealand, and Barbados. However, mortality rates did not follow those of incidence. The highest mortality rates fell mainly in countries with lower HDI (Fig. S1b), including the Caribbean (e.g., Barbados, Jamaica, Haiti, Saint Lucia, Bahamas, Trinidad and Tobago) and Africa (e.g., Benin, Cabo Verde, Zimbabwe, Liberia, Côte d'Ivoire). The calculated MIRs ranged from 0.081 (France) to 0.844 (Afghanistan). The lowest MIRs were achieved in highly developed countries (Fig. 1b), such as France, Ireland, Italy, Spain, United States, Luxemburg, Israel, Australia, and Japan. Whereas low-to-medium HDI countries owned the highest MIRs (Afghanistan, Guinea, Pakistan, Liberia, Uzbekistan, Cambodia and Nepal).
It was estimated that bladder cancer ranked the 10th most common cancer with 549,000 new cases and 200,000 deaths in 2018. Bladder cancer was most common to happen in high-to-very high HDI regions (Fig. S1c), especially European countries (Greece, Denmark, Hungary, Netherlands, Albania, Italy, Germany, Spain), although the highest rates were in Lebanon. However, the top 10 countries with highest MIRs of bladder cancer were all from low-HDI group (Fig. 1c), consisting of Africa (Niger, Comoros, Central African, Djibouti, Liberia, Guinea-Bissau, Guinea, Uganda, Chad) and Timor-Leste. The lowest MIR was 0.119 in Iceland.
403,000 cases of kidney cancer and 175,000 related deaths occurred in 2018. New kidney cancer diagnoses were made most in very-high HDI European countries (Fig. S1e) (Belarus, Latvia, Lithuania, Czech Republic, Estonia, Slovakia, France, Hungary, Iceland, Croatia). Similarly, the distribution of MIRs of kidney cancer was from 0.165 (Korea) to 0.950 (Mali) (Fig. 1d). The lowest MIRs were achieved in very-high HDI group like Korea, Bahamas, Luxembourg, United States, Canada, Norway, Italy, Australia, and Japan. While the lowest were obtained from low-HDI African countries (Mali, Chad, South Sudan, Burkina Faso, Guinea, Sierra Leone, Eritrea).
3.2 The correlation between urologic cancer MIR and national HDI
The global MIR of prostate, bladder and kidney cancer in 2018 was 0.358, 0.251, and 0.410, respectively (Fig. 1b-d). As the above described distribution of urologic cancer MIR and developing degree, we analyzed their relationship in mathematical regression. We found that as the level of national HDI increased, the corresponding urologic cancer MIR was relatively lower, with strong correlation (prostate: r = -1.059, p < 0.0001 for 2018, r = -1.425, p < 0.0001 for 2012; bladder: r = -1.049, p < 0.0001 for 2018, r = -0.918, p < 0.0001 for 2012; kidney: r = -1.153, p < 0.0001 for 2018, r = -1.231, p < 0.0001 for 2012). We also applied nonlinear regression analysis on data, verifying the existence of a “dose-to-response” inhibitory effect between HDI values and MIRs (Fig. 2a-b, d-e, g-h). The HDI values at half maximal MIR (HDI50) of prostate, bladder and kidney cancer in 2018 was 0.639, 0.704 and 0.736, respectively.
We further compared the MIRs of urologic cancer among 4-tier HDI groups and clarified the persistent disparities associated with HDI levels (p < 0.0001, One-way ANOVA). Take prostate cancer in 2018 for example, the mean MIR in very-high HDI countries (0.224) was significantly lower than that in high- (0.424), medium- (0.522), or low- (0.641) HDI countries (p < 0.0001, Tukey's post hoc test; Fig. 2c). Similar results were obtained in other cancer sites (bladder, kidney) as well as data in 2012 (p < 0.0001, Tukey's post hoc test; Fig. 2f, i).
3.5 Temporal transition of urologic cancer burdens and outcomes fromm 2012 to 2018
It was reported that urologic cancers had a cumulative 2.1 million new cases worldwide in 2013, nearly 2.5-fold the number in 1990 [2]. Our study updated the transition of urologic cancer outcomes from 2012 to 2018 with latest data.
3.5.1 Prostate cancer
Incidence and mortality rates of prostate cancer have risen considerably since the end of last century [2]. Nevertheless, it should be noted that between 2012 and 2018, new prostate cases decreased from 1276706 to 1111689, and fell from 358989 to 307417 in deaths. In general, the MIR of prostate cancer did not change much during the past 6 years (0.251 vs 0.259). We plotted national HDIs and MIRs in 2018 and 2012 together and noticed similar distributions (Fig. 5a). Notably, there is an evident change that linear regression line has shifted to the lower-left direction from 2012 to 2018, most obviously among countries with lower HDIs. Furthermore, within both low- and medium- HDI groups, the national MIRs in 2018 decreased significantly in comparison to the 2012 data (p < 0.0001 for both groups, Mann-Whitney test; Fig. 2c). In high HDI groups, there was only decreasing tendency without significance (0.424 vs 0.460, p > 0.05; Fig. 2c). The survival rates generally increased, with only 7 out of 57 countries dropped more than 1% (p < 0.05; paired t-test) (Fig. 5b; Table 1).
Table 1
National HDI and 5-year net survival values of prostate cancer from 2012 to 2018
|
2012
|
|
2018
|
|
Transitions in a decade
|
Country
|
HDI
|
Survival
|
|
HDI
|
Survival
|
|
ΔHDI
|
Δsurvival
|
Algeria
|
0.713
|
50.3
|
|
0.754
|
64.1
|
|
0.041
|
13.8
|
Argentina
|
0.811
|
83.6
|
|
0.825
|
87.6
|
|
0.014
|
4
|
Australia
|
0.938
|
93.2
|
|
0.939
|
94.5
|
|
0.001
|
1.3
|
Austria
|
0.895
|
90.8
|
|
0.908
|
90.2
|
|
0.013
|
-0.6
|
Belgium
|
0.897
|
93.2
|
|
0.916
|
93.8
|
|
0.019
|
0.6
|
Brazil
|
0.73
|
92.5
|
|
0.759
|
91.6
|
|
0.029
|
-0.9
|
Bulgaria
|
0.782
|
54.8
|
|
0.813
|
68.3
|
|
0.031
|
13.5
|
Canada
|
0.911
|
94.2
|
|
0.926
|
93.6
|
|
0.015
|
-0.6
|
Chile
|
0.819
|
84.4
|
|
0.843
|
82
|
|
0.024
|
-2.4
|
China
|
0.699
|
62.5
|
|
0.752
|
69.2
|
|
0.053
|
6.7
|
Colombia
|
0.719
|
87.8
|
|
0.747
|
80.3
|
|
0.028
|
-7.5
|
Costa Rica
|
0.773
|
92.6
|
|
0.794
|
93.2
|
|
0.021
|
0.6
|
Croatia
|
0.805
|
78.3
|
|
0.831
|
80.9
|
|
0.026
|
2.6
|
Cuba
|
0.78
|
53.8
|
|
0.777
|
71.4
|
|
-0.003
|
17.6
|
Cyprus
|
0.848
|
98.3
|
|
0.869
|
99.2
|
|
0.021
|
0.9
|
Czech Republic
|
0.873
|
81.5
|
|
0.888
|
85.3
|
|
0.015
|
3.8
|
Denmark
|
0.901
|
82.5
|
|
0.929
|
85.6
|
|
0.028
|
3.1
|
Ecuador
|
0.724
|
80.7
|
|
0.752
|
82.2
|
|
0.028
|
1.5
|
Estonia
|
0.846
|
83.2
|
|
0.871
|
86.3
|
|
0.025
|
3.1
|
Finland
|
0.892
|
93.4
|
|
0.920
|
93.2
|
|
0.028
|
-0.2
|
France
|
0.893
|
93.6
|
|
0.901
|
93.1
|
|
0.008
|
-0.5
|
Germany
|
0.92
|
91.8
|
|
0.936
|
91.6
|
|
0.016
|
-0.2
|
Iceland
|
0.906
|
89.7
|
|
0.935
|
90.8
|
|
0.029
|
1.1
|
India
|
0.554
|
33.2
|
|
0.640
|
44.3
|
|
0.086
|
11.1
|
Ireland
|
0.916
|
89.7
|
|
0.938
|
91.1
|
|
0.022
|
1.4
|
Israel
|
0.9
|
95.7
|
|
0.903
|
95.6
|
|
0.003
|
-0.1
|
Italy
|
0.881
|
89.6
|
|
0.880
|
89.5
|
|
-0.001
|
-0.1
|
Japan
|
0.912
|
91.4
|
|
0.909
|
93
|
|
-0.003
|
1.6
|
Jordan
|
0.7
|
88.6
|
|
0.735
|
86.1
|
|
0.035
|
-2.5
|
Korea, Republic of
|
0.909
|
87.3
|
|
0.903
|
89.9
|
|
-0.006
|
2.6
|
Kuwait
|
0.79
|
71.9
|
|
0.803
|
84
|
|
0.013
|
12.1
|
Latvia
|
0.814
|
88.8
|
|
0.847
|
90.4
|
|
0.033
|
1.6
|
Lithuania
|
0.818
|
93.8
|
|
0.858
|
94.3
|
|
0.040
|
0.5
|
Malaysia
|
0.769
|
74.9
|
|
0.802
|
87.7
|
|
0.033
|
12.8
|
Malta
|
0.847
|
86.4
|
|
0.878
|
88.2
|
|
0.031
|
1.8
|
Mauritius
|
0.737
|
61.8
|
|
0.790
|
63.5
|
|
0.053
|
1.7
|
Netherlands
|
0.921
|
87.5
|
|
0.931
|
88.5
|
|
0.010
|
1
|
New Zealand
|
0.919
|
89.3
|
|
0.917
|
90.3
|
|
-0.002
|
1
|
Nigeria
|
0.471
|
73.9
|
|
0.532
|
58.7
|
|
0.061
|
-15.2
|
Norway
|
0.955
|
90.3
|
|
0.953
|
92.9
|
|
-0.002
|
2.6
|
Poland
|
0.821
|
75
|
|
0.865
|
78.1
|
|
0.044
|
3.1
|
Portugal
|
0.816
|
90
|
|
0.847
|
90.9
|
|
0.031
|
0.9
|
Qatar
|
0.834
|
98.2
|
|
0.856
|
89.6
|
|
0.022
|
-8.6
|
Romania
|
0.786
|
78.2
|
|
0.811
|
77.1
|
|
0.025
|
-1.1
|
Russian Federation
|
0.788
|
68.6
|
|
0.816
|
79.3
|
|
0.028
|
10.7
|
Singapore
|
0.895
|
86.7
|
|
0.932
|
87.8
|
|
0.037
|
1.1
|
Slovakia
|
0.84
|
74.4
|
|
0.855
|
74.7
|
|
0.015
|
0.3
|
Slovenia
|
0.892
|
83.2
|
|
0.896
|
85
|
|
0.004
|
1.8
|
South Africa
|
0.629
|
38.6
|
|
0.699
|
37.8
|
|
0.070
|
-0.8
|
Spain
|
0.885
|
90.4
|
|
0.891
|
89.7
|
|
0.006
|
-0.7
|
Sweden
|
0.916
|
90.1
|
|
0.933
|
90.7
|
|
0.017
|
0.6
|
Switzerland
|
0.913
|
88.6
|
|
0.944
|
89.2
|
|
0.031
|
0.6
|
Thailand
|
0.69
|
71.8
|
|
0.755
|
68
|
|
0.065
|
-3.8
|
Turkey
|
0.722
|
81.2
|
|
0.791
|
83.8
|
|
0.069
|
2.6
|
United Kingdom
|
0.875
|
86.7
|
|
0.922
|
88.7
|
|
0.047
|
2
|
United States of America
|
0.937
|
98.1
|
|
0.924
|
97.4
|
|
-0.013
|
-0.7
|
Uruguay
|
0.792
|
84.7
|
|
0.804
|
86.5
|
|
0.012
|
1.8
|
Note: A total of 57 countries with survival rates available in both years; HDI, Human Development Index. |
3.5.2 Bladder cancer
New bladder cancer diagnoses shrank nearly a quarter between 2012 and 2018 (549 393 vs 429 793). It is remarkable that MIR of bladder cancer in 2018 had a slight increase when compared with 2012, though not significantly (0.358 vs 0.333; p > 0.05, Fig. 2f, Fig. 5c). There was also only tiny fluctuation between MIR of 2012 and 2018 within each specific HDI group (Fig. 2f).
3.5.3 Kidney cancer
The incidence of kidney cancer also reduced during 2012–2018 (337 860 vs 403 262). In the scatter diagram of HDI-MIR, current MIR of kidney cancer also shifted in the direction of lower-left when comparing with 2012 (Fig. 5d). Remarkably, two regression lines were nearly parallel (r2018 = -1.153, r2012 = -1.231; p < 0.01, Mann-Whitney test). Meanwhile, MIRs of kidney cancer declined overall, across all development status (p < 0.01 for the low-, p < 0.0001 for the medium-, p < 0.001 for the high-, and p = 0.23 for the very-high-HDI group, Mann-Whitney test; Fig. 2i).