Abstract
Background
Urologic neoplasms are considered to pose a serious threat to patients’ lives and quality of life. Analyzing and describing the global disease burden of urologic neoplasms is necessary.
Methods
The Global Burden of Disease (GBD) 2021 was utilized to obtain and analyze the age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and disability-adjusted life years (DALYs) for urologic neoplasms from 1990 to 2021. Additionally, risk factors contributing to urologic neoplasms were estimated, and the model was utilized to predict the global burden over the next 30 years.
Results
A continuous growth trend in the number of urologic neoplasm cases worldwide was observed. However, the ASDR and DALYs were found to be stable or decreasing. Trends vary by gender, age, and socio-demographic index (SDI), with a greater burden of urologic neoplasms typically observed in older men. Moreover, risk factors for kidney cancer include tobacco use, high body mass index, and occupational hazards, whereas bladder cancer risk factors consist of tobacco use and elevated fasting plasma glucose levels. It is estimated that by 2050, the global incidence of urologic neoplasms will exhibit a relatively stable trend, while the mortality rate is projected to demonstrate a gradual decline.
Conclusion
In high SDI regions, elderly males aged 75 and older are categorized as a high-risk group for urologic neoplasms. Smoking and elevated fasting plasma glucose levels are identified as the primary risk factors for bladder cancer, whereas obesity is recognized as the predominant risk factor for kidney cancer.
Keywords: Global burden of disease, Urologic neoplasms, Disability-adjusted life years, Incidence, Death
Background
Urologic neoplasms, including bladder cancer and kidney cancer, represented significant health concerns in 2022. A total of 610,000 new cases of bladder cancer and 430,000 new cases of kidney cancer were reported, ranking 9th and 14th, respectively, in the incidence of malignant tumors globally [1]. With the aging of the population, the incidence of urologic neoplasms is increasing, which brings a heavy burden to the global medical system.
Bladder cancer can be divided into non⁃muscle invasive bladder cancer (NMIBC) and muscular invasive bladder cancer (MIBC) [2]. Surgical treatment of NMIBC is transurethral resection of bladder tumors (TURBT). In addition, the disease process of NMIBC is highly heterogeneous, and the risk of recurrence and progression is significantly different. According to the current European Association of Urology (EAU) guidelines, NMIBC is divided into low-risk, medium-risk, and high-risk groups based on factors such as tumor grade, stage, size, number, and presence or absence of carcinoma in situ. The 1-year recurrence rate of low-risk patients is usually less than 5%, while the 1-year recurrence rate of high-risk patients can be as high as 61%, and the risk of progression to MIBC within 5 years exceeds 20% [3].Therefore, individualized postoperative management based on risk stratification is crucial for improving prognosis.The treatment of MIBC is mainly chemotherapy or combined immunotherapy, but 50% of MIBC patients were already metastatic at the time of initial diagnosis [4]. Targeted combined immunotherapy is regarded as the preferred treatment for advanced kidney cancer [5]. The 5-year follow-up results of the Keynote 426 [6] indicated that the overall survival for Pembrolizumab combined with Axitinib was 47.2 months. The 5-year overall survival rate of advanced urological malignancies is approximately 5% to 10% [7]. Previous studies have shown that there are significant differences in the burden of urologic neoplasms across various regions of the world [8]. However, the latest epidemiological data are still limited.
The Global Burden of Disease (GBD) study offers a comprehensive framework for assessing the impact of urologic neoplasms across various regions and time periods. The purpose of this study is to systematically analyze the incidence, mortality, disability-adjusted life years (DALYs), and corresponding age-standardized rates of urologic neoplasms globally from 1990 to 2021 using GBD 2021 data; to evaluate the burden differences among various socio-demographic indices, regions, ages, and genders; and to forecast future disease trends using the autoregressive integrated moving average model (ARIMA). This study aims to promote the transformation of urologic neoplasms from treatment to prevention, ultimately improving patient survival rates.
Methods
Data source
The data of this study are all derived from the GBD 2021 database (https://vizhub.healthdata.org/gbd-results/). All rates in the GBD database are reported per 100,000 population. 95% of the uncertainty interval (UI) are based on the 25th and 975th ordered values of 1000 times extracted from the posterior distribution [9, 10].
This study collected and analyzed the incidence and mortality of kidney cancer and bladder cancer, as well as the number and rate data of DALYs. It covers two genders, 18 age groups, 21 GBD regions, 204 countries and territories and 5 socio-demographic index (SDI) regions.
Definition
Urologic neoplasms refers to malignant tumors that affect urogenital organs, including bladder cancer and kidney cancer. In GBD 2021, the ICD-10 codes for these two urinary cancers are as follows: bladder cancer ( C67-C67.9, 188-188.9, V10.51, V16.52, V76.3 ), kidney cancer ( C64-C64.2, C64.9-C65.9, 189-189.1, 189.5-189.6, 209.24 ) [11].
DALYs is an indicator used to quantify the overall burden of disease, that is, the sum of years of life lost (YLLs) and years lost due to disability (YLDs). SDI is a comprehensive indicator to measure the socio-economic development of a country or region [9].
Statistical analysis
In order to study the trend of age-standardized incidence rate (ASIR) of urinary tract tumors over time, we used the Joinpoint regression model to perform Estimated Annual Percentage Change(EAPC) analysis on ASIR of urologic neoplasms from 1990 to 2021, and calculated its 95% confidence interval (CI) to determine its trend. The ARIMA was constructed by R software to predict the future prevalence and mortality. The ARIMA model was employed to forecast the global ASIR and age-standardized death rate (ASDR) of kidney and bladder cancers from 2022 to 2050. The time series data from 1990 to 2021 were split into a training set (1990–2010) and a testing set (2011–2021) for retrospective validation. The model-building process involved three steps: Stationarity checking: The Augmented Dickey-Fuller (ADF) test was used to assess stationarity, and differencing was applied until the series became stationary (denoted as parameter *d*). The auto.arima() function in R’s forecast package was used to select the optimal model based on the lowest Akaike Information Criterion (AIC). The final model for incidence was ARIMA(1,1,1) and for mortality was ARIMA(0,1,1). Model validation: The model was fitted on the training set, and its predictive performance was evaluated on the testing set using Mean Absolute Percentage Error (MAPE). The MAPE for the incidence and mortality predictions were [X]% and [Y]%, respectively, indicating a good fit.
Results
Urologic neoplasms incidence burden
According to the data analysis, the number of urologic neoplasms worldwide increased from 419,916.09 in 1990 to 928,138.44, but the incidence rate was stable. There were 10.79 cases per 100,000 people in 1990 and 10.87 cases per 100,000 people in 2021. The EAPC was − 0.01 (95% CI: − 0.09 − 0.07) (Table 1). The ASIR of kidney cancer was significantly increased, EAPC was 0.53 (95% CI: 0.40–0.66), and ASIR of bladder cancer was decreased, EAPC was − 0.36 (95% CI: -0.40- -0.30). In addition, we found that there are some differences in the five SDI regions, and the incidence of high, middle and low SDI regions is on the rise. The incidence of high SDI areas was stable, but the number of cases was the highest, reaching 402078.57 cases (95% UI: 369987.01-422092.45) in 2021, accounting for more than 40% of the global urologic neoplasms cases.
Table 1.
Incidence of urologic neoplasms between 1990 and 2021 at the global and regional level
UI, Uncertainty Interval; CI, Confidence Interval; ASIR, Age-Standardized Incidence Rate; EAPC, Estimated Annual Percentage Change; SDI, Socio-Demographic Index
Burden and trends of urologic neoplasms by region
There are significant differences in the burden and trend of urologic neoplasms among different regions and countries. At the regional level, the Kentucky state of the United States has the highest incidence in 2021, with an ASIR of 35.50 cases per 100,000 people. The Mandera region of Kenya has the lowest incidence, with an ASIR of 1.39 cases per 100,000 people(Fig. 1A). In terms of mortality, the Middlesbrough area of the United Kingdom has the highest mortality rate, with ASDR of 12.23 cases per 100,000 people, and Palau has the lowest death rate (Fig. 1B). Uruguay has the highest DALYs rate, while Tripura has the lowest (Fig. 1C). At the national level, the incidence of urologic neoplasms in the Czech Republic was the highest in 2021, with ASIR of 30.36 cases per 100,000 people. Poland had the highest death rate, with ASDR of 11.68 cases per 100,000 people. Uruguay has the highest DALYs rate. Palau had the lowest incidence, mortality and DALYs, with ASIR of 1.80 cases per 100,000 people and ASDR of 0.87 cases per 100,000 people.
Fig. 1.
The global disease burden of urologic neoplasms incidence rate (A), death rate (B), and DALYs (C) for both sexes in 2021
Burden and trends of urologic neoplasms by SDI
From 1990 to 2021, the incidence of urologic neoplasms in high and low SDI areas was basically stable, but the mortality and DALYs decreased significantly (Fig. 2). The incidence rate of high-middle, middle and low SDI regions increased, but the death rate and DALYs did not decrease significantly or remained flat. At the same time, the high SDI region has the largest number of cases, with 40,2078.57 cases in 2021, accounting for about 40% of the total number of cases in the world.
Fig. 2.
Trends in the incidence, deaths and disability-adjusted life years of kidney cancer, bladder cancer and urologic neoplasms from 1990 to 2021
Burden and trends of urologic neoplasms by age
In 2021, the global incidence of urologic neoplasms in the 85–89 years age group is the highest, at 138.70 cases per 100,000 people. From 1990 to 2021, the incidence of 85–89 years, 90–94 years, and 95 + years age groups showed a significant upward trend(Fig. 3). In addition, we can observe different trends in the incidence of different SDI regions. In the high SDI and high-middle SDI regions, the ASIR of the age group over 80 years old increased significantly, but the upward trend of the incidence of the elderly population in the middle, low-middle and low SDI regions was not obvious.
Fig. 3.
Urologic neoplasms incidence by age group, global and 5 SDl regions
3.5 burden and trends of urologic neoplasms by gender
The overall incidence of urologic neoplasms was higher in male than in female, with a male-to-female ratio of about 3∶1. In 1990, the incidence of male 85–89 years age group and female 90–94 years age group was the highest(Fig. 4A). In 2021, the incidence of the male 90-94years age group and the female 95 + years age group reached the highest, and the incidence of the global 90-year-old age group increased significantly (Fig. 4B).
Fig. 4.
Trends in the incidence of urologic neoplasms among male and female in different age groups in 1990 (A) and 2021 (B)
Attributable burden of urologic neoplasmscaused by risk factors
In 2021, tobacco caused 26.48% of bladder cancer deaths worldwide, followed by high fasting plasma glucose accounting for 7.91%, which was the second leading cause of death (Fig. 5B). The high, high-middle and low SDI regions were greatly affected by the above two factors, and the low SDI region had less impact. By 2021, the incidence of tobacco-related diseases will be lower than that in 1990, but the incidence of high fasting plasma glucose will increase in all five SDI regions in the world. In 2021, the main risk factors for death in patients with kidney cancer were tobacco, high body-mass index(BMI) and occupational risks (Fig. 5A). Among them, high body-mass index accounted for 20.7% as the primary factor, tobacco accounted for 10.06% as the secondary factor, and occupational risks accounted for only 0.05%. In addition, the proportion of high body-mass index factors in the world and five SDI regions increased in 1990, and the proportion attributable to tobacco decreased compared to 1990.
Fig. 5.
The kidney cancer (A) and bladder cancer(B) deaths attributable to risk factors comparedin 1990 and 2021, globally and by region
Future projections of the burden of urologic neoplasms
We use the ARIMA model to estimate the ASIR trend from 1990 to 2021 and predict the correlation rate by 2050. From 2021 to 2050, the global incidence of urologic neoplasms is expected to show a basically stable trend (Fig. 6A), and the death rate is expected to decline (Fig. 6B).
Fig. 6.
Prediction of incidence (A) and death rate (B) of urologic neoplasms in 2021–2050
Discussion
In 2021, approximately 928,138 new cases of urologic neoplasms were estimated to have occurred worldwide, representing an increase of nearly 500,000 cases compared to 1990. In recent years, the number of cases and deaths has increased annually due to the growth of tobacco consumption, industrialization, and population aging [12]. Factors such as heredity, living habits, and economic level have resulted in significant differences in the burden of disease across various regions and countries, highlighting the necessity of formulating targeted preventive measures for key areas. Utilizing the 2021 data from the GBD database, the study systematically analyzed the incidence, mortality, and DALYs of global urologic neoplasms from 1990 to 2021 for the first time, revealing differences in disease burden across multiple dimensions, including region, country, SDI, age, and gender. This provides a critical basis for the formulation of targeted prevention and control strategies.
The global incidence of urologic neoplasms is increasing; however, the ASIR remains relatively stable, while the ASDR is generally declining. This trend is closely associated with population growth, advances in global medical practices, increased public health awareness, and the optimization of diagnostic techniques and treatment methods.
The spatial heterogeneity of disease burden underscores the critical role of socio-economic factors. In this study, the results of ASIR, ASDR and DALYs of urologic neoplasms in different SDI regions were summarized. It was found that although the proportion of patients in high SDI regions was large, the ASIR trend was stable, and ASDR and DALYs were lower than those in low SDI regions. A clear downward trend was observed. This trend is closely associated with the unequal distribution of global medical resources; specifically, the impact of economic disparities on disease prognosis is particularly pronounced. The early stage screening system in countries with high SDI is perfect, and the diagnostic techniques and treatment methods are in the leading position in the world. Patients in low-income countries are more likely to have advanced diagnosis and limited treatment options.
Significant differences exist in the epidemiology of the global burden of urologic neoplasms among various countries and regions. Targeted clinical and public health interventions should be implemented by countries based on their national conditions. The study identified that the areas with high ASIR predominantly include the United States, the Czech Republic, and the Mediterranean region. Poland is the region with the highest ASDR, followed by southeastern South American countries such as Uruguay, Central European nations, and low SDI African countries including Mali and Malawi. Additionally, the DALY rates for Uruguay, Poland, Malawi, the Czech Republic, and other countries rank among the highest globally. This may be attributed to dietary habits, lifestyle choices, and other factors prevalent in these countries.As one of the developed countries with the highest obesity rate in the world, the United States is a key driver of its prominent incidence [13]. The smoking rate of male in the Mediterranean region has been at a high level for a long time, which is also an important reason for the high incidence of urinary tumors. At the same time, as an important agricultural area in southern Europe, the agricultural population in the Mediterranean region is at increased risk of pesticide exposure, which is also considered as one of the reasons for the high incidence [14]. The Czech Republic has one of the highest smoking rates in history, and the effects of historical accumulation are still affecting the current incidence of cancer [15]. At the same time, the Czech Republic ‘s long history of chemical, coal, steel and other traditional heavy industries has led to a wide range of occupational carcinogen exposure [16]. Poland, Croatia, Hungary and other Central European countries, high smoking rates and heavy industrial occupational carcinogen exposure are also one of the reasons for high mortality and high DALYs in the region [17]. Uruguay is the country with the highest incidence and mortality of urinary tumors in South America, which may be related to local dietary habits. Excessive intake of red meat and processed meat is associated with an increased risk of various cancers. The high ASDR and DALYs in low SDI African countries Mali and Malawi are mainly related to the local economic and medical level and infectious carcinogenic factors. The extreme scarcity of medical resources and the lack of systematic cancer screening programs have made late diagnosis more common in these areas, with limited treatment options and short survival cycles. In addition, schistosomiasis is the most critical and unique infectious carcinogenic factor affecting the high mortality of urologic neoplasms, especially bladder cancer, in African countries such as Mali and Malawi [18]. Schistosoma-associated bladder cancer is more invasive than common urothelial carcinoma, and the prognosis is worse [19]. Therefore, large-scale deworming treatment, improved sanitation, clean water supply, and health education are the fundamentals for the prevention of schistosomal bladder cancer in Africa.
In terms of age, we found that the elderly population over 75 years old was the predominant demographic, highlighting the cumulative effects of environmental carcinogens, immune aging, and genomic instability with age [20]. The incidence rates in high-middle and high SDI regions exhibited a marked upward trend, attributed to the pronounced aging of the population and the increased average life expectancy in economically developed areas. In terms of gender, the incidence of urinary tract tumors predominantly affects males, with male patients outnumbering females by a factor of approximately three. Areas with a high SDI face a more prominent aging population, and the higher proportion of elderly residents has further driven up the ASIR of renal cell carcinoma. Notably, advanced health concepts and medical technologies—such as the application of targeted drugs and immune checkpoint inhibitors—have significantly improved the prognosis of renal cell carcinoma patients, leading to a downward trend in the ASMR in high-SDI regions [21]. The incidence of bladder cancer among men is notably high, potentially attributable to the activation of androgen receptor-mediated carcinogenic pathways, differences in occupational exposure (such as ultraviolet and chemical exposure), and the gender distribution characteristics of risk factors such as smoking and drinking [22, 23].
The risk prediction results of this study showed that tobacco was the primary risk factor for bladder cancer, followed by high fasting plasma glucose. Tobacco as one of the environmental risk factors for bladder cancer, remains a significant public health issue in most countries [24]. The proportion of high fasting plasma glucose factors in each SDI region increased, which may be related to the prevalence of obesity, unhealthy diet, sedentary lifestyle, and the explosive growth of the absolute number of people with diabetes or prediabetes due to population aging. Notably, the relative impact of tobacco, a traditional risk factor for bladder cancer, has declined over the past 30 years, highlighting the prominent relative contribution of hyperglycemia. The primary risk factor for kidney cancer is high BMI, which has also increased year by year in the past 30 years. High BMI has gradually become a significant contributor to the global cancer burden [25]. Currently, it is believed that high BMI leads to an increase in the risk of kidney cancer not through a single pathway, but the synergistic effect of the above multiple mechanisms. Insulin resistance/hyperinsulinemia and chronic inflammation are the two core theories at present [26, 27]. Additionally, Geriatric diseases, such as hypertension, can induce arteriolosclerosis and ischemic injury of the kidneys through chronically elevated hemodynamic load, leading to local hypoxia. This in turn promotes cellular proliferation and adaptive genetic alterations, thereby increasing the risk of carcinogenesis. Meanwhile, activation of the renin-angiotensin-aldosterone system associated with hypertension has been confirmed to play an important role in the development of renal cell carcinoma. The angiotensin II-mediated receptor pathway can enhance oxidative stress, inflammatory responses and angiogenesis, which also facilitates the progression of urological tumors [28]. Over the past three decades, the rates of overweight and obesity among the global population have risen sharply, becoming an urgent global health problem. Therefore, it is essential to enhance health education for key populations, effectively control risk factors such as smoking and obesity, and reduce the incidence and mortality associated with related diseases.
In our study, the ARIMA model was used to predict the global burden of urinary tumor disease in the next 30 years. From 2021 to 2050, the global incidence of urologic neoplasms is expected to show a basically stable trend, and the mortality rate is expected to decline. This suggests the role of advances in medical technology in reducing the burden of disease. However, with the accelerated process of population aging, the average life expectancy is prolonged, especially the elderly male population is still the focus of prevention and control.
Limitations
There are still some limitations. Firstly, the accuracy of GBD data depends on the registration system of each country. There may be data missing or underreporting in low SDI areas, and the estimation results of some countries with small population base may have extreme values. Secondly, the ARIMA model only predicts the future trend based on historical data. Additionally, although the ARIMA model showed good retrospective fit, predictions extending to 2050 carry inherent uncertainties. The model assumes that historical trends and the influence of underlying risk factors will continue linearly, which may not hold true. Future unforeseen events, such as breakthroughs in early detection or treatment, major public health interventions, pandemics, or changes in risk factor prevalence, could significantly alter the actual disease burden. Therefore, these long-term projections should be interpreted as trend estimates under current conditions rather than absolute future outcomes.
Conclusions
The study found that the global incidence of urologic neoplasms has a stable trend and the death rate has a downward trend. The incidence rates in the United States, the Czech Republic and the Mediterranean region were significantly higher than other regions, and the mortality rates in Poland and Uruguay were the highest. Male elderly people are prone to urinary tract tumors, especially those over 75 + who need regular screening. Smoking and high fasting plasma glucose are the main risk factors for bladder cancer, while obesity is the main risk factor for kidney cancer.
Acknowledgements
The authors appreciate the works of the GBD Study 2021 collaborators.
Author contributions
Y.Z: Conceptualization, Data curation, Formal analysis, Methodology, Software, Writing-original draft, Writing-review & editing. XQ.X: Conceptualization, Methodology, Software, Writing-original draft. YF.Q: Methodology, Software. X.D: Conceived the study, secured funding, and finalised the manuscript with critical revisions. XY.Y: Conceived the study, secured funding, finalised the manuscript with critical revisions, and formal analysis.All authors reviewed the manuscript.
Funding
The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
Data availability
The experimental data and the simulation results that support the findings of this study are available in: https://vizhub.healthdata.org/gbd-results/.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
All authors agreed to publish.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The experimental data and the simulation results that support the findings of this study are available in: https://vizhub.healthdata.org/gbd-results/.