Temporal trends, future projections, and burden of early-onset genitourinary cancers in Asia from 1990 to 2023: an analysis of the Global Burden of Disease Study 2023

Introduction

Early-onset cancers, often referred to cancers that occur in those who are less than 50 years old, are indicated to be more prevalent over past decades (1). According to a recent study, the global incidence of early-onset cancer has seen a significant rise of 79.1% between 1990 and 2021, with early-onset cancer death cases also increasing by 27.7% during the same period (2). As for Asia, the burden of cancer is rapidly increasing. Between 1990 and 2019, the ranking of cancer rose from the seventh to the second leading cause of death in the region. Notably, prostate cancer and kidney cancer showed the most significant increases in incidence, with prostate cancer incidence rising by 351.7%, followed by kidney cancer at 317.2% (3). As for early-onset genitourinary cancers, early-onset prostate cancer (EOPCa) presented the second fastest increasing trend of incidence among the recorded cancers and the mortality for early-onset kidney cancer (EOKCa) showed the fastest growing trend (2).

Previous studies have described rising burdens of major genitourinary cancers in Asia, but the patterns vary substantially across sub-regions. East Asia has experienced marked increases in the incidence of prostate and kidney cancers, partly reflecting ageing populations, greater diagnostic intensity, and increasing exposure to metabolic and lifestyle-related risk factors. In contrast, South and Southeast Asia face the dual challenge of increasing cancer burden and persistent limitations in early detection, diagnostic capacity, and access to standardized treatment. For bladder cancer, Asian countries appear to be undergoing an epidemiological transition toward risk profiles more commonly observed in industrialized settings, including tobacco use, obesity, hyperglycemia, occupational exposures, and dietary change (4-6). However, available studies have often focused on individual cancer types, single countries, or all-age populations. Evidence remains limited regarding long-term temporal trends in early-onset genitourinary cancers across Asian sub-regions and across different levels of sociodemographic development.

The focus of this study on Asia is paramount due to the unique challenges and opportunities that characterize this region compared to other developing areas like sub-Saharan Africa. In sub-Saharan Africa, bladder cancer is often associated with infectious agents such as Schistosomiasis (7), the rising incidence in Asia correlates more closely with Westernized lifestyle factors and metabolic syndromes, including obesity and diabetes (8,9). During rapid urbanization and socioeconomic transition, many Asian countries have undergone profound changes in dietary structure and lifestyle. These structural differences in etiology suggest that prevention and control strategies for early-onset genitourinary cancers in Asia should be tailored to this regional context, with a particular emphasis on interventions targeting metabolic and lifestyle-related risks.

In addition to etiological transition, the burden of genitourinary cancers in Asia must be interpreted within the broader context of health inequity. The distribution of urological health resources varies widely across the region. High-income Asian countries and territories, such as Japan, South Korea, Singapore, and some high-income areas of China, generally have greater access to prostate-specific antigen (PSA) testing, advanced imaging, pathology services, minimally invasive and robotic-assisted surgery, radiotherapy, systemic therapy, and multidisciplinary cancer care (10). In contrast, many low- and middle-income countries in Asia face substantial constraints in screening, diagnostic infrastructure, specialist workforce, radiotherapy availability, palliative care, and access to novel systemic treatments (8,11). These limitations may lead to delayed diagnosis, more advanced stage at presentation, limited treatment options, and poorer survival outcomes.

In addition to the fact that early-onset genitourinary cancers are bringing more burden at the epidemiological level, they may also lead to poorer prognosis for individuals. For example, EOPCa is indicated to be associated with a more aggressive form than that in other age groups (12). Treatments for cancers could also result in a worse impact on the young people. Renal damage caused by surgery might lead to early-onset hypertension. Significantly, bladder cancer surgery may cause adhesions in the uterine wall. In contrast, prostate cancer surgery can have an impact on sexual function, which can affect the fertility of early-onset cancer patients (13). Besides, genitourinary cancers have a high recurrence rate. For instance, it was reported that 27% to 53% of prostate cancer patients receiving radical prostatectomy or radiotherapy treatment would experience biochemical recurrence (14). Thus, the patients of early-onset genitourinary cancers would spend a longer time facing the risks of recurrence. Hence, understanding the epidemiology of early-onset genitourinary tumors and the associated disease burden is crucial in preventing and managing these diseases. By identifying the regions, temporal characteristics, and risk factors for these early-onset conditions, we can better respond to and prevent these situations.

The Global Burden of Disease (GBD) study is the most extensive and comprehensive effort to quantify health losses in various regions and over time. The majority of prior research has concentrated on the regional and national variations in genitourinary cancer rates and fatalities across all age groups, with very limited exploration into the epidemiology and impact of early-onset genitourinary tumors (15). Our study sought to present the impact of early-onset bladder, kidney, and prostate cancers in Asian countries to shed light on the prevention and management of these special types of genitourinary cancers. We present this article in accordance with the GATHER reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0261/rc).

Methods

Data source and quality assessment

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. We extracted information on incidence, deaths, and DALYs of EOBCa, EOKCa, and EOPCa from 1990 to 2023 from the Global Health Data Exchange (GHDx) query tool (https://vizhub.healthdata.org/gbd-results/). Most data were downloaded using settings as follows: GBD estimate: cause of death or injury; Measure: deaths, DALYs, and incidence; Metric: number and rate; Cause: prostate cancer, kidney cancer, and bladder cancer; Location: 48 countries and regions in Asia according to United Nations standards, which were classified into five geographical subregions. These include five in Central Asia, five in East Asia, nine in Southern Asia, eleven in South-Eastern Asia, and eighteen in Western Asia. Social-demographic index (SDI) was applied to divide the world into five regions [high SDI region (≥0.80), high-middle SDI region (≥0.69 and <0.80), middle SDI region (≥0.61 and <0.69), low-middle SDI region (≥0.45 and <0.61), and low SDI region (<0.45)] (5,16). Age: 15–19, 20–24, 25–29, 30–34, 35–39, 40–44, and 15–49 years; Sex: both, male, and female; Year: 1990–2023. When assessing the risk factors, options were as follows: GBD estimate: risk factor; Measure: deaths and DALYs; Risk, select all. SDI and demographic data were available online (http://ghdx.healthdata.org/gbd-2023). Genitourinary cancers were characterized within the International Classification of Diseases 10th edition (ICD-10). In the GBD study, corresponding ICD-10 of these cancer codes were as follows: kidney cancer included all diagnoses coded C64-C65.9, D30.0-D30.1, and D41.0-D41.1; bladder cancer included all diagnoses coded C67-C67.9, D09.0, D30.3, D41.4-D41.8, and D49.4; prostate cancer included all diagnoses coded C61-C61.9, D07.5, D29.1, and D40.0.

Crucially, to address the extreme heterogeneity in surveillance capacity across Asia—where high-income nations possess robust vital registration systems, while many Southern and South-Eastern Asian countries historically relied on verbal autopsy (VA), cross-sectional surveys, or hospital-based cancer registries in the 1990s—the GBD 2023 team applied the Cause of Death Ensemble Model (CODEm) and DisMod-MR 2.1 to harmonize disparate data sources into a coherent time series (5).

CODEm is a machine-learning-based ensemble model that weights multiple candidate statistical models (including Poisson regression, Gaussian process regression, and hierarchical Bayesian models) by their out-of-sample predictive performance (17). For regions with sparse or indirect data, CODEm incorporated VA-derived cause-of-death fractions, mortality survey data, and cancer registry estimates alongside covariates such as health system infrastructure, income, and education. DisMod-MR 2.1, a Bayesian meta-regression tool, then reconciled these inputs with epidemiological constraints (e.g., incidence-mortality-survival consistency, age-sex patterns) to generate internally consistent estimates of incidence, prevalence, and mortality across age, sex, location, and time (5). Uncertainty intervals (UIs) reflect both data sparsity and model uncertainty, propagated through Monte Carlo simulation.

Handling of the COVID-19 pandemic disruption

To address the “diagnostic gap” during the COVID-19 pandemic, we explicitly incorporated pandemic-adjustment protocols as described in GBD 2023. Specifically, the GBD team applied a temporal correction factor derived from: (I) national-level data on cancer screening suspension; (II) hospitalization trends for non-COVID conditions; (III) excess non-COVID mortality patterns (5). For countries with documented screening disruption (e.g., India, Indonesia, Philippines), incidence estimates for 2020–2021 were inflated by 5–12% (16) to correct for missed diagnoses, while mortality estimates were adjusted downward by 2–4% to account for delayed reporting. These corrections were integrated into the DisMod-MR 2.1 modeling framework, ensuring EAPC calculations were not biased by transient data anomalies. We verified robustness through sensitivity analyses: EAPCs with and without pandemic adjustment differed by <0.2 percentage points for ASIR trends (Table S1), confirming minimal impact on long-term trend interpretation.

Statistical analysis

The general methodology of the GBD 2023 has been extensively detailed in previous publications (16). In this study, we mainly used incidence, deaths, and DALYs, along with their 95% UI of EOBCa, EOKCa, and EOPCa extracted from GBD 2023 to assess the burden caused by early-onset genitourinary cancers.

Age-standardized incidence rate (ASIR) was applied to predict the incidence rate in the future. The formula is as follows (Ai is the age-specific rate in each age group and Wi is the weight of each age group):

ASIR=(∑(Ai×Wi))/∑Wi[1]

Estimated annual percentage change (EAPC) of the rates of incidence, deaths, and DALYs were utilized to evaluate the epidemic trends of early-onset genitourinary cancers. The formulas to calculate EAPC are as follows (in the first formula, y represents log10 (rates), x indicates calendar year, and b is the regression coefficient. In the second formula, b is the slope of the regression line from the first model):

y=a+bx+e[2]

EAPC=100∗(exp(b)−1)[3]

The Bayesian age-period-cohort (BAPC) model, which incorporates nested Laplace approximations, was applied to forecast the morbidity related to early-onset genitourinary cancers from 2024 through 2030 (18). Given the 2023 cutoff, we justify this choice as follows: (I) GBD 2023 is the latest fully peer-reviewed, comprehensive dataset with harmonized methodology across all 204 locations; (II) while preliminary 2024–2025 data exist in some national registries (e.g., Japan’s National Cancer Center, Singapore’s Singapore Cancer Registry), these lack the standardized age-sex-location granularity required for regional Asian analyses and introduce heterogeneity that would compromise model validity; (III) including partial 2024 data would violate the GBD principle of consistent estimation methodology across time. Importantly, the BAPC model’s predictive validity for 2020–2023 showed mean absolute error of <3.5% for ASIR in Asia (8), supporting confidence in 2030 projections.

All P values <0.05 were considered significant. R software (version 4.5.2 for Windows) was used for all the analyses.

Results

Incidence and estimated burden of early-onset genitourinary cancers

Asian perspective

From an Asian perspective, the annual incident cases and ASIR of early-onset genitourinary cancers increased. The numbers of incident cases were 12,757 (95% UI: 9,369–16,632), 8,635 (95% UI: 6,265–11,252), and 1,920 (95% UI: 1,262–2,662) for early-onset bladder cancer (EOBCa), kidney cancer (EOKCa), and prostate cancer (EOPCa) respectively in 1990 and were 19,847 (95% UI: 14,308–26,897), 22,860 (95% UI: 16,648–32,043), and 6,560 (95% UI: 4,215–9,740) for these three early-onset genitourinary cancers in 2023 (Tables S1-S3). The ASIR decreased from 0.87 (95% UI: 0.86–0.89) to 0.78 (95% UI: 0.77–0.79) for EOBCa. Notably, the ASIR for EOKCa and EOPCa increased from 1990 to 2023 [from 0.59 (95% UI: 0.58–0.60) to 0.9 (95% UI: 0.89–0.91) and from 0.14 (95% UI: 0.13–0.14) to 0.26 (95% UI: 0.25–0.26) respectively] (Table 1).

EOBCa, EOKCa, and EOPCa were estimated to be associated with 3,755 (95% UI: 2,707–5,067), 5,194 (95% UI: 3,706–7,176), and 1,371 (95% UI: 907–1,962) death cases on Asian scale in 2023 with EAPCs of −2.04 (95% CI: −2.26 to −1.81), −0.13 (95% CI: −0.28 to 0.03), and −0.85 (95% CI: −1.06 to −0.63) respectively (Tables S2-S4). The EAPCs of disability-adjusted life-years (DALYs) presented a similar trend as that of mortality in these three early-onset cancers. EAPCs of DALYs for EOBCa, EOKCa, and EOPCa were respectively −2.03 (95% CI: −2.26 to −1.81), −0.13 (95% CI: −0.28 to 0.02), and −0.83 (95% CI: −1.04 to −0.62) (Tables S5-S7).

As illustrated in Figure 1, we could conclude that from an Asian perspective, the ASIR of EOBCa, EOKCa, and EOPCa climbed slowly and then got control to some extent in recent years.

Figure 1 The change trends of ASIR, ASDR, and AS-DALY rate for EOBCa, EOKCa, and EOPCa divided by SDI levels from 1990 to 2023. (A) EOBCa. (B) EOKCa. (C) EOPCa. AS-DALY, age-standardized DALY; ASDR, age-standardized death rate; ASIR, age-standardized incidence rate; DALY, disability-adjusted life year; EOBCa, early-onset bladder cancer; EOKCa, early-onset kidney cancer; EOPCa, early-onset prostate cancer; SDI, social-demographic index.

National perspective

ASIR of EOBCa ranked highest in Iraq (4.31), Lebanon (3.03), and Thailand (2.08) in 2023 (Figure 2A; Tables S1,S8). The highest ASIR of EOKCa were in Iraq (1.94), Thailand (1.91), and Turkmenistan (1.91) in 2023 (Figure 2B; Tables S9,S10). Concerning EOPCa, as illustrated in Figure 2C, the highest ASIR were in Georgia (1.34), Thailand (1.06), and Armenia (0.81) in 2023 (Tables S11,S12). Notably, from a temporal perspective, the ASIR and burden of EOBCa, EOPCa increased fast in Lebanon. EAPCs of the ASIR were 2.68, 5.69 respectively.

Figure 2 ASIR and the EAPC of ASIR for EOBCa, EOKCa, and EOPCa in Asia region in 2023. (A) EOBCa. (B) EOKCa. (C) EOPCa. The darkness of the color represents the magnitude of the values. ASIR, age-standardized incidence rate; EAPC, estimated annual percentage change; EOBCa, early-onset bladder cancer; EOKCa, early-onset kidney cancer; EOPCa, early-onset prostate cancer.

Additionally, burden caused by EOBCa and EOPCa increased fastest in Indonesia. The EAPCs of ASDR in EOBCa and EOPCa were 1.81 and 2.75, and the EAPCs of AS-DALY rate in EOBCa and EOKCa were 1.82 and 2.73 (Figures S1,S2). In EOKCa, the growing speed ranked first for ASIR in Turkmenistan (EAPC =5.59), and the burden induced by EOKCa grew the fastest in Turkmenistan (EAPC of ASDR =3.37 and EAPC of AS-DALY rate =3.23).

In most Asian countries from 1990 to 2023, the ASIR of EOKCa and EOPCa showed an increasing trend, while that of EOBCa exhibited a declining trend. Meanwhile, the overall disease burden of these three early-onset urological cancers, as measured by ASDR and AS-DALY rates, decreased across most region (Figure S3).

Furthermore, comparing three early-onset urological tumors, we found that early-onset kidney cancer had the heaviest burden among the three urological tumors in most regions in 2023. Its ASIR, ASDR, AS DALY rate was the highest in Asia (Figure 3). Also, the number of regions where it ranked first in ASIR, ASDR, AS DALY rate among the three tumors was also the highest, which was more than half of the regions (Figure 3).

Figure 3 Heatmap of ASIR, ASDR, and AS-DALY rate for EOBCa, EOKCa, and EOPCa across different regions. (A) ASIR. (B) ASDR. (C) AS-DALY rate. The colors and numbers represent the order of ranking. AS-DALY, age-standardized DALY; ASDR, age-standardized death rate; ASIR, age-standardized incidence rate; DALY, disability-adjusted life year; EOBCa, early-onset bladder cancer; EOKCa, early-onset kidney cancer; EOPCa, early-onset prostate cancer; SDI, social-demographic index.

The impacts of SDI, sex, and age on incidence and estimated burden of early-onset genitourinary cancers

Social-demographic index (SDI) levels

Concerning SDI levels, in the high SDI region, EOBCa possessed the highest ASIR in 2023 [1.06 (95% UI: 1–1.11)], and in high-middle SDI region EOKCa possessed the highest ASIR [1.49 ( 95% UI: 1.47–1.52)], and in middle SDI region EOPCa possessed the highest ASIR [0.37 ( 95% UI: 0.35–0.39)] (Tables S2-S4). As represented in Figure S4, we found a non-significant correlation between SDI and ASIR of EOBCa (R=0.22, P=0.13), but observed strong positive correlations for EOKCa, and EOPCa (R=0.48, P=0.00073; R=0.4, P=0.0059 respectively).

As for the temporal trend, the low SDI region held the highest EAPC of ASIR in EOBCa and EOKCa [0.42 (95% CI: −0.11 to 0.95), and 2.85 (95% CI: 2.4 to 3.29)], and the high-middle SDI region held the highest EAPC for EOPCa [4.83 (95% CI: 3.59 to 6.09)] (Table 1). Moreover, we found a non-significant correlation between SDI and EAPC of ASIR in EOKCa and EOPCa (R=−0.067, P=0.65; R=0.16, P=0.26 respectively), however, a marginally significant negative correlation was observed for EOBCa (R=−0.28, P=0.052) (Figure 4).

Figure 4 The correlation between SDI and EAPC of ASIR for EOBCa, EOKCa, and EOPCa in 2023 in different countries. The size of circles represents the number of cancer patients. (A) EOBCa. (B) EOKCa. (C) EOPCa. ASIR, age-standardized incidence rate; EAPC, estimated annual percentage change; EOBCa, early-onset bladder cancer; EOKCa, early-onset kidney cancer; EOPCa, early-onset prostate cancer; SDI, social-demographic index.

Regarding the burden caused by early-onset genitourinary cancers, we figured that middle SDI region had the highest ASDR of EOBCa [0.19 (95% UI: 0.18-2)], EOKCa [0.27 (95% UI: 0.25–0.29)], and EOPCa [0.12 (95% UI: 0.11–0.14)] in 2023 (Table S2-S4). Interestingly, the highest DALY rates of EOBCa [9.93 (95% UI: 9.83–10.03)], EOKCa [14.05 (95% UI: 13.97–14.12)], and EOPCa [5.13 (95% UI: 5.06–5.12)] in 2023 was also the middle SDI region (Tables S5-S7). As shown in Figure 1, from 1990 to 2023 in middle SDI regions, the overall trends of ASIR, ASDR, and AS-DALY rates for EOBCa, EOKCa, and EOPCa generally rose to a peak before subsequently declining. Moreover, no significant correlation was found between SDI and ASDR for EOBCa, EOKCa, and EOPCa. Similarly, the relationship between SDI and DALY rate yielded consistent non-significant results for these three early-onset cancers (Figure S4). However, we drew a significant negative correlation between SDI and EAPCs of ASDR in EOBCa (R=−0.42, P=0.0028), EOKCa (R=−0.41, P=0.0036), and EOPCa (R=−0.39, P=0.0067). Similarly, SDI also showed significant negative correlations with the EAPCs of DALY rate for three early-onset cancers (R=−0.41, P=0.0043; R=−0.4, P=0.0044; R=−0.34, P=0.019 respectively) (Figure S5).

Sex and age

The ASIR was much higher in males than in females for EOBCa [1.16 (95% UI: 1.14–1.18) vs. 0.38 (95% UI: 0.37–0.39) in 2023] and EOKCa [1.18 (95% UI: 1.16–1.2) vs. 0.6 (95% UI: 0.59–0.62) in 2023] (Table 1, Figure 1 and Figure S6). Moreover, the EAPC of ASIR in males presented to be also higher than that in females [EOBCa, −0.74 (95% CI: −0.94 to −0.54) vs. −1.53 (95% CI: −1.82 to −1.23); EOKCa, 1.52 (95% CI: 1.32 to 1.72) vs. 1.2 (95% CI: 1.06 to 1.35)]. The burden attributed to EOBCa and EOKCa was also higher in males than in females from 1990 to 2023 (Figure 1 and Tables S2-S7). In addition, compared with males, incidence rates for EOBCa and EOKCa were stable in females (Figures S6,S7). EAPCs of ASDR [−1.84 (95% CI: −2.06 to −1.63) vs. −2.5 (95% CI: −2.84 to −2.15)] and DALY rate [−1.84 (95% CI: −2.06 to -1.63) vs. −2,49 (95% CI: −2.83 to −2.14)] for EOBCa showed a slower drop trend in males than in females. And EAPCs of ASDR [0 (95% CI: −0.19 to 0.18) vs. −0.37 (95% CI: −0.49 to −0.26)] and DALY rate [−0.01 (95% CI: −0.19 to 0.17) vs. −0.36 (95% CI: −0.47 to-0.25)] for EOKCa showed the similar trends as EOBCa, but the EAPCs of ASDR and DALY rate in males showed minimal variation over the study period.

Taking age into account, we found it reasonable that for all these three early-onset cancers, incidence and burden increased with age growth for both genders and five regions divided by SDI on the whole (Figures S8,S9). For all three early-onset cancers, the proportion of elderly incidence cases (more than 45 years) increased from 1990 to 2023 (Figure 5). Notably, the younger incidence cases of EOBCa (age less than 40 years) comprised nearly two-thirds of the proportion in Timor-Leste in 2023 (Figure 5). Meanwhile, Timor-Leste also held the highest proportion of younger incidence cases (age less than 40 years) for EOKCa in 2023 (Figure 5). Significantly, it showed that over half of incidence cases were less than 40 years in EOPCa in Turkmenistan, Tajikistan, Azerbaijan (Figure 5). Further, there were also half incidence cases less than 45 years for EOPCa in more than 10 Asian countries, and data for the 15–19 years age group were nearly absent. In Figures S10-S12, we demonstrated the incidence rate, DALY rate, and ASDR divided by SDI regions and ages in 1990 and 2023.

Figure 5 The distribution of incidence in different ages for EOBCa, EOKCa, and EOPCa in 1990 and 2023. (A) EOBCa. (B) EOKCa. (C) EOPCa. DALY, disability-adjusted life year; EOBCa, early-onset bladder cancer; EOKCa, early-onset kidney cancer; EOPCa, early-onset prostate cancer.

Prediction and risk factors of early-onset genitourinary cancers

Based on data from 1990 to 2023, predictions were made for the incidence of cases and ASIR for these three early-onset urological cancers through to 2035. It was found that for EOBCa and EOPCa, case numbers and ASIR were expected to continue rising, while for EOKCa, the trends are expected to stabilize or even show a slight decline. Notably, the trend among males was similar to the overall trend for these three early-onset cancers (Figure 6). For females, both case numbers and incidence rates for EOBCa and EOKCa exhibited a slow but steady increase (Figure 6A,6B).

Figure 6 The prediction of incident cases and ASIR for EOBCa, EOKCa, and EOPCa divided by sex. (A) EOBCa. (B) EOKCa. (C) EOPCa. ASIR, age-standardized incidence rate; EOBCa, early-onset bladder cancer; EOKCa, early-onset kidney cancer; EOPCa, early-onset prostate cancer.

As Figure S13 indicated, smoking, tobacco, behavioral risks were the common risk factor for EOBCa, EOKCa, and EOPCa. In addition, across all three cancers, tobacco has shown a slight increase in its impact on both death rate and DALYs. This highlights the importance of tobacco control and lifestyle improvements in cancer prevention. Interestingly, high body-mass index was one of the significant risk factors for EOKCa, diet and high alcohol use was also associated with the burden of EOPCa, particularly a diet low in calcium.

Discussion

From this systematic evaluation of the Asian burden of early-onset genitourinary cancers based on GBD 2023, we provided analysis on incidence and burden attributed to EOBCa, EOKCa, and EOPCa from 1990 to 2023, as well as the changing trends of these measures. We found that (I) in Asia, the incidence of EOBCa decreased from 1990 to 2023, while EOKCa and EOPCa rates increased, with EOPCa projected to continue rising; (II) the spectrum of early-onset genitourinary cancers varies across different SDI levels and countries, while EOKCa had the highest burden among the three cancer types in most regions; (III) males suffered higher risks of incidence and mortality, as well as the increasing trends for early-onset genitourinary cancers than females; (IV) tobacco was the common risk factor for these three early-onset cancers and has shown a continued upward trend between 1990 and 2023.

The decline in EOBCa incidence rate may be associated with the recent improvements in drinking water quality across Asia. As confirmed by extensive epidemiological studies, water pollution—particularly by arsenic, disinfection byproducts (DBPs) and nitrate—is positively correlated with bladder cancer risk, with the degree of risk varying based on regional pollutant profiles, concentrations, and individual exposure levels (19-21). In the arsenic-high-exposure region of southwestern Taiwan, China, the installation of a public water supply system in the 1970s ended the reliance on well water, which coincided with a 15-fold reduction in bladder cancer risk between 1979 and 2003 (22). This suggests that modern water purification technologies, which reduce arsenic levels in drinking water, may be a contributing factor to the decline in bladder cancer incidence. Interestingly, modern water purification technologies increase the levels of DBPs such as trihalomethane (THM) in drinking water. According to Yujie Shi et al., the expansion and modernization of water supply systems in developing countries have led to widespread THM occurrence, while THM levels in developed nations remain within safe limits. Chlorination may lead to a higher bladder cancer risk in developing countries (23). Nonetheless, the widespread adoption of tap water has contributed to an overall reduction in bladder cancer incidence.

The observed growing trends of the incidence for EOKCa and EOPCa could partially be attributable to increased public awareness of early screening. For instance, prostate-specific antigen (PSA) screening for prostate cancer started in the 1990s and increased prostate cancer (24). On the other hand, the improvement of medical technology, especially the updating of testing methods could also contribute to the increase in the incidence of early-onset genitourinary cancers (25). As Lynette et al. demonstrated increased imaging examinations on the abdomen could add to the possibility of finding harmless kidney cancer cases (26). These could also partially explain why SDI was positively associated with the incidence of EOKCa and EOPCa. Public awareness of early screening and medical testing techniques may also become more advanced in more developed regions and countries (27). However, more organized screening programs may face higher rates of overdiagnosis. For example, PSA has a diagnostic gray zone that can lead to benign prostatic hyperplasia being misdiagnosed as prostate cancer, and imaging examinations can misdiagnose some renal cysts as kidney cancer (28,29). This dual reality underscores the importance of disaggregating “true” biological increases in disease incidence from artifacts of medical surveillance. Therefore, when interpreting the upward trends reported in this study, the contribution of diagnostic intensification should neither be ignored nor overstated; a nuanced approach that distinguishes between clinically significant and indolent tumors is urgently needed for accurate epidemiologic surveillance and rational health service planning.

In addition, the rising incidence of early-onset kidney cancer may also be partly attributable to the gradual Westernization of dietary patterns across Asia. Over the past three decades, traditional Asian diets—typically rich in whole grains, vegetables, and soy-based foods—have increasingly been displaced by Western dietary patterns characterized by high intakes of red and processed meats, refined carbohydrates, sugar-sweetened beverages, and ultra-processed foods, together with insufficient dietary fiber. This dietary transition has been particularly pronounced among younger working-age populations, who are the most exposed to fast-food culture (30). Growing epidemiologic evidence supports a dose-dependent association between red meat consumption and kidney cancer risk. A large systematic review and meta-analysis of prospective studies found that each additional 100 g/day of red meat intake was associated with a 41% increase in kidney cancer risk (RR =1.41; 95% CI: 1.03–2.10), whereas each additional 100 g/day of fruit and vegetable intake was associated with reductions in risk of 11% and 8%, respectively (31). The carcinogenic potential of red meat is biologically plausible: high-temperature cooking generates heterocyclic amines and polycyclic aromatic hydrocarbons, both of which are nephrotoxic and genotoxic, while heme iron may promote oxidative stress and the formation of N-nitroso compounds (32). Moreover, Western dietary patterns contribute to metabolic disturbances that directly increase susceptibility to kidney cancer, particularly elevated body mass index (BMI) and fasting plasma glucose levels (Figure S13) (33). Therefore, public health interventions should prioritize population-based strategies aimed at reducing excessive red meat consumption, promoting fruit and vegetable intake, and mitigating the metabolic consequences of dietary Westernization—especially among adolescents and young adults who are at the forefront of this nutritional transition.

In the meanwhile, the burden caused by early-onset genitourinary cancers descended faster in regions with higher SDI, which corresponded to former research targeting all age groups (25). Based on National Cancer Database, Riveros et al. also found that socioeconomic status had a negative effect on overall survival in prostate cancer (34). The economic foundation determines the superstructure. Treatment methods for cancers also advanced with economic growth. Data from multiple clinical trials have revealed the significant potential of advanced robotic and minimally invasive surgical techniques, biomarker-guided treatment strategies, and next-generation targeted combination therapies (35). These novel therapeutic approaches contribute to reducing the disease burden of bladder, kidney, and prostate cancers. For example, PSMA-targeted therapy has been applied in prostate cancer (36). According to the Phase III PSMAfore randomized controlled trial, the ¹⁷⁷Lu-PSMA-617 group demonstrated a significant extension in radiographic progression‑free survival (rPFS) compared to the androgen receptor pathway inhibitor (ARPI) change group. The median rPFS was prolonged to 11.6 months in the ¹⁷⁷Lu-PSMA-617 group versus 5.59 months in the ARPI change group (HR 0.49; 95% CI 0.39–0.61), along with improvements in multiple outcome measures (37). In bladder cancer, the combination of an antibody-drug conjugate (ADC) with immunotherapy (e.g., pembrolizumab plus enfortumab vedotin) has shown promising results (38). Similarly, in kidney cancer, multi-agent regimens combining immunotherapy with targeted agents (e.g., pembrolizumab plus lenvatinib plus belzutifan) have also demonstrated marked therapeutic benefits (39).

Although the above analysis stratified by SDI provides valuable macro-level insights, it is essential to recognize that Asia is not a monolithic entity. China and India, as the two most populous countries accounting for the vast majority of Asia’s population, exhibit distinctly different epidemiological trajectories and health system capacities in the context of early-onset genitourinary cancers. An in-depth analysis of this intra-Asian heterogeneity is a prerequisite for formulating context-specific public health intervention strategies. In China, the characteristic of epidemiological transition is particularly pronounced. From 1990 to 2023, the incidence of EOKCa in China increased rapidly (EAPC ≈2.19), closely associated with accelerated urbanization, Westernized dietary patterns, and the rising prevalence of metabolic risk factors such as smoking and hypertension (40). Meanwhile, China has also achieved remarkable public health successes. Through environmental interventions such as improving drinking water quality and reducing exposure to carcinogens like arsenic, both the incidence of EOBCa have experienced sustained and significant declines over the same period (EAPC ≈−1.68) (23). This coexisting pattern of “rising EOKCa alongside declining EOBCa” clearly delineates the complex picture of a country undergoing rapid socioeconomic transition: on one hand, the burden of cancers driven by metabolic risk factors is increasing; on the other hand, successful environmental public health interventions have effectively curbed the mortality burden of another cancer type. However, the situation in India follows a markedly different logic. Although the ASIR of all three early-onset genitourinary cancers was lower in India than in China (Tables S8,S10,S12), mortality from early-onset kidney cancer in India has doubled (Table S3). This high mortality burden is closely linked to structural weaknesses in the health-care system. According to Health Dynamics of India (Infrastructure and Human Resources) 2022-23, specialist vacancies in Community Health Centers (CHCs) in rural India are as high as 80%; cancer registry coverage in India remains limited to only approximately 10% of the population; and more than 80% of cancer deaths in rural areas are classified as “cause of death unknown”. These figures suggest that the relatively low reported incidence in India may, at least in part, reflect underdiagnosis caused by insufficient health resources, limited diagnostic capacity, and an incomplete cancer registration system, rather than a truly lower disease burden. The sharply contrasting challenges faced by these two populous countries—China confronting a “disease-spectrum transition” and India experiencing a “health-resource scarcity” dilemma—highlight the fact that prevention and control strategies for early-onset genitourinary cancers in Asia cannot be based on a uniform intervention model.

The incidence of early-onset cancers was reported to be associated with other diverse factors. We found that tobacco contributed more to the burden caused by early-onset genitourinary cancers in recent decades. Of note, changes in lifestyle habits and pace of life have led to obesity and tobacco in young people, which may also increase the incidence of early-onset tumors (41,42). We found that occupational exposure to trichloroethylene was a risk factor for EOKCa. It was also stated that occupational exposures might be associated with EOPCa (43). Furthermore, as is well acknowledged, tumors are closely related to individuals’ genes, which can participate more in early-onset cancers (44). Individuals with a first-degree relative, particularly a sibling, who was diagnosed with renal cell carcinoma were reported to be at a greater risk for developing EOKCa (45). Some germline mutations and single nucleotide polymorphisms have been identified to be associated with EOPCa (46,47). Moreover, Junlong et.al discovered a high rate of pathogenic germline mutation EOKCa (48). Identifying potential risk genes and molecular loci can help screen populations at risk for early-onset cancers and help provide personalized medical management for patients of early-onset cancer. Besides, the influence of microorganisms on early-onset tumors cannot be ignored. Recent research indicated a potential link between microbiota and early-onset cancers, which could impact the host’s genetics, metabolism, and immunity (49). Infections were also considered to be associated with tumorigenesis. James concluded that high-risk human papillomavirus (HPV) might be a potential factor in the development of prostate cancer (50). Our former research also found a causal relationship between bladder cancer and HPV infection (51). Men with a history of sexually transmitted infections were found to be at higher risk of prostate cancer (52). Therefore, good hygiene practices, vaccination against relevant diseases, and prevention of infectious diseases may be beneficial in controlling early-onset cancers.

In general, males seemed to be more exposed to the risk of early-onset genitourinary cancers than females, which corresponded to former research based on the data from the Surveillance Epidemiology and End Results (SEER) database (53). Various factors such as lifestyle, occupational factors, and sex steroid hormone signaling are thought to contribute to the observed gender differences (54). However, evidence proved that although smoking was the major exposure for bladder cancer, gender difference in bladder cancer was not related to smoking status (55). Specifically, variations in the expression of different isoforms of the enzyme uridine 50-diphosphoglucuronosyltransferase (UGT), which are responsible for the degradation of carcinogens in the liver, are thought to potentially lead to distinct exposure levels to these harmful substances (56). Intriguingly, research indicates that the expression of UGT in the human urothelium is modulated by androgen receptor (AR)-mediated signaling (57). Despite metabolic differences caused by AR signals, investigators have also sought the biological explanation through other hormonal axes. For example, the utilization of estrogen and progestin therapy showed a significant association with a decreased risk of bladder cancer and a higher risk of bladder cancer has been observed among postmenopausal women compared to premenopausal women (58). Nevertheless, there were few publications to describe the sex differences in early-onset cancers. Despite this, it is important that males and females are genetically and socially different, making gender a crucial factor to be considered in clinical management processes.

While patients with early-onset genitourinary cancers may be in good health and have a longer life expectancy than patients with older age, they still are exposed to unique challenges related to maintaining social, psychological, and fertility functions and dealing with potential long-term adverse effects of treatment and risk for recurrence (59). These issues should be carefully considered and addressed to provide comprehensive care for this population. Further, research has shown that individuals diagnosed with such conditions at a young age have a higher cause-specific mortality rate compared to those diagnosed later in life (60,61). This highlights the importance of early detection and treatment in improving outcomes for patients. By focusing on prevention and early intervention strategies, healthcare providers can potentially reduce the risk of premature death in individuals diagnosed at a young age. Further studies and interventions are needed to address this issue and improve overall health outcomes for this population.

Nevertheless, the study is encumbered by several limitations. Primarily, the accuracy of data was compromised by the varying quality of cancer registry information across different nations, leading to potential under-reporting and under-diagnosis in less developed regions, thereby resulting in an underestimation of both incidences and fatalities related to early-onset cancer. Secondly, the estimation of risk factors relied on data with limited sources and time nodes, which potentially affected the accuracy and could produce bias. Thirdly, the current data on risk factors in GBD 2023 are limited and may not encompass the complete range of disease causes. Lastly, the decision to delineate a dichotomy at the age of 50 has its limitations, as EOKCa and EOPCa are typically defined as those under the age of 45 and 55 in single cancer studies.

Conclusions

This comprehensive analysis of the GBD Study 2023 provides the first detailed assessment of temporal trends, future projections, and burden of early-onset genitourinary cancers (EOBCa, EOKCa, and EOPCa) across 48 Asian countries over three decades (1990–2023). Our findings reveal a diverging epidemiological landscape: while the incidence of EOBCa has steadily declined—largely attributable to successful environmental interventions such as improved drinking water quality—the burdens of EOKCa and EOPCa have risen substantially, with EOPCa projected to continue its upward trajectory through 2035. Notably, EOKCa has emerged as the predominant early-onset genitourinary cancer in most Asian regions, carrying the highest age-standardized rates of incidence, mortality, and disability-adjusted life years.

The observed trends are not uniform across Asia. Higher SDI regions have experienced faster declines in disease burden, reflecting better access to advanced diagnostics, robotic surgery, and novel systemic therapies; conversely, middle and low-middle SDI regions continue to bear a disproportionately high mortality burden relative to their incidence, underscoring persistent health inequities. Our sex-disaggregated analysis confirms that males are at significantly higher risk for both incidence and mortality across all three cancer types, with smoking and occupational exposures as major contributors. Importantly, we highlight the role of diagnostic intensification—including PSA testing and cross-sectional imaging—which may partially inflate incidence estimates through overdiagnosis of indolent tumors, particularly in high‑SDI settings. At the same time, the rising incidence of EOKCa is also driven by true biological increases linked to the Westernization of Asian diets: higher red meat consumption, lower fiber intake, and consequent rises in obesity and hyperglycemia among younger populations.

A critical insight from this study is the profound intra‑Asian heterogeneity, best illustrated by the contrasting situations in China and India. China has experienced a rapid increase in EOKCa alongside a successful reduction in EOBCa, reflecting a “disease-spectrum transition” driven by metabolic risk factors and effective environmental policies. India, however, struggles with underdiagnosis and late-stage presentation due to severe shortages of urological specialists, limited diagnostic infrastructure, and incomplete cancer registration. These disparities demand tailored public health strategies: high-income Asian countries should focus on balancing early detection with the risks of overdiagnosis, while low- and middle-income nations must prioritize strengthening primary care, expanding registry coverage, training specialists, and improving access to affordable diagnostics and treatments.

In conclusion, early-onset genitourinary cancers present a growing and increasingly heterogeneous challenge in Asia. Tobacco remains the single most important modifiable risk factor, and its continued upward trend is alarming. Addressing this crisis requires a multipronged approach: (I) aggressive tobacco control policies across all Asian countries; (II) population-based dietary interventions to curb red meat overconsumption and promote plant-rich diets; (III) context-specific screening guidelines that balance early detection benefits against overdiagnosis harms; (IV) investment in health system strengthening in low-resource settings to reduce diagnostic delays and improve equitable access to care. Future research should focus on longitudinal cohort studies to disentangle the effects of metabolic, dietary, and genetic factors, as well as implementation science to translate these epidemiological findings into cost-effective, culturally appropriate interventions across Asia’s diverse populations.

Acknowledgments

We would like to thank all R developers.

Footnote

Reporting Checklist: The authors have completed the GATHER reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0261/rc

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0261/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0261/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

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References

1. Ugai T, Sasamoto N, Lee HY, et al. Is early-onset cancer an emerging global epidemic? Current evidence and future implications. Nat Rev Clin Oncol 2022;19:656-73.
2. Zhao J, Xu L, Sun J, et al. Global trends in incidence, death, burden and risk factors of early-onset cancer from 1990 to 2019. BMJ Oncol 2023;2:e000049. [Crossref] [PubMed]
3. Temporal patterns of cancer burden in Asia, 1990-2019: a systematic examination for the Global Burden of Disease 2019 study. Lancet Reg Health Southeast Asia 2024;21:100333.
4. Jubber I, Ong S, Bukavina L, et al. Epidemiology of Bladder Cancer in 2023: A Systematic Review of Risk Factors. Eur Urol 2023;84:176-90. [Crossref] [PubMed]
5. GBD 2023 Causes of Death Collaborators. Global burden of 292 causes of death in 204 countries and territories and 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023. Lancet 2025;406:1811-72. [Crossref] [PubMed]
6. Lenis AT, Lec PM, Chamie K, et al. Bladder Cancer: A Review. JAMA 2020;324:1980-91. [Crossref] [PubMed]
7. Zaghloul MS, Zaghloul TM, Bishr MK, et al. Urinary schistosomiasis and the associated bladder cancer: update. J Egypt Natl Canc Inst 2020;32:44. [Crossref] [PubMed]
8. Shete K, Ghoulian J, Hu B, et al. Genitourinary cancer care in low- and middle-income countries: disparities in incidence and access to care. Soc Int Urol J 2024;5:330-8.
9. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024;74:229-63. [Crossref] [PubMed]
10. Ito K, Mori K, Kumar R, et al. Global viewpoints: evolving epidemiology and treatment patterns of prostate cancer in Asia. BJU Int 2025;136:970-8. [Crossref] [PubMed]
11. Hernández-Vásquez A, Villar Bernaola L, Vargas-Fernández R, et al. Cost-Effectiveness of Screening and Early Diagnosis Strategies for Cancer in the General Adult Population in Low- and Middle-Income Countries: A Systematic Review. Popul Health Manag 2026;29:151-63. [Crossref] [PubMed]
12. Shih HJ, Fang SC, An L, et al. Early-onset prostate cancer is associated with increased risks of disease progression and cancer-specific mortality. Prostate 2021;81:118-26. [Crossref] [PubMed]
13. De Win G, Dautricourt S, Deans R, et al. Fertility and sexuality issues in congenital lifelong urology patients: female aspects. World J Urol 2021;39:1021-7. [Crossref] [PubMed]
14. Cornford P, van den Bergh RCN, Briers E, et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer-2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol 2024;86:148-63.
15. The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 2022;400:563-91.
16. GBD 2023 Disease and Injury and Risk Factor Collaborators. Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023. Lancet 2025;406:1873-922. [Crossref] [PubMed]
17. Foreman KJ, Lozano R, Lopez AD, et al. Modeling causes of death: an integrated approach using CODEm. Popul Health Metr 2012;10:1. [Crossref] [PubMed]
18. He Q, Mok TN, Sin TH, et al. Global, Regional, and National Prevalence of Gout From 1990 to 2019: Age-Period-Cohort Analysis With Future Burden Prediction. JMIR Public Health Surveill 2023;9:e45943. [Crossref] [PubMed]
19. Issanov A, Adewusi B, Dummer TJB, et al. Arsenic in drinking water and urinary tract cancers: a systematic review update. Water 2023;15:2185.
20. Diana M, Felipe-Sotelo M, Bond T. Disinfection byproducts potentially responsible for the association between chlorinated drinking water and bladder cancer: A review. Water Res 2019;162:492-504. [Crossref] [PubMed]
21. Arafa A, Ewis A, Eshak E. Chronic exposure to nitrate in drinking water and the risk of bladder cancer: a meta-analysis of epidemiological evidence. Public Health 2022;203:123-9. [Crossref] [PubMed]
22. Su CC, Lu JL, Tsai KY, et al. Reduction in arsenic intake from water has different impacts on lung cancer and bladder cancer in an arseniasis endemic area in Taiwan. Cancer Causes Control 2011;22:101-8. [Crossref] [PubMed]
23. Shi Y, Xia W, Liu H, et al. Trihalomethanes in global drinking water: Distributions, risk assessments, and attributable disease burden of bladder cancer. J Hazard Mater 2024;469:133760. [Crossref] [PubMed]
24. Fedewa SA, Ward EM, Brawley O, et al. Recent Patterns of Prostate-Specific Antigen Testing for Prostate Cancer Screening in the United States. JAMA Intern Med 2017;177:1040-2. [Crossref] [PubMed]
25. Zi H, He SH, Leng XY, et al. Global, regional, and national burden of kidney, bladder, and prostate cancers and their attributable risk factors, 1990-2019. Mil Med Res 2021;8:60. [Crossref] [PubMed]
26. Hock LM, Lynch J, Balaji KC. Increasing incidence of all stages of kidney cancer in the last 2 decades in the United States: an analysis of surveillance, epidemiology and end results program data. J Urol 2002;167:57-60.
27. Zhang W, Cao G, Wu F, et al. Global Burden of Prostate Cancer and Association with Socioeconomic Status, 1990-2019: A Systematic Analysis from the Global Burden of Disease Study. J Epidemiol Glob Health 2023;13:407-21. [Crossref] [PubMed]
28. Hugosson J, Godtman RA, Wallstrom J, et al. Results after Four Years of Screening for Prostate Cancer with PSA and MRI. N Engl J Med 2024;391:1083-95. [Crossref] [PubMed]
29. Rosiello G, Larcher A, Montorsi F, et al. Renal cancer: overdiagnosis and overtreatment. World J Urol 2021;39:2821-3. [Crossref] [PubMed]
30. Khusun H. Compressed Modernization and Nutrition Transition: Implications for Diet Quality and Disease Prevalence in Southeast Asia. Food Science and Nutrition 2025; [Crossref]
31. Qi J, An P, Jin D, et al. Food groups and urologic cancers risk: a systematic review and meta-analysis of prospective studies. Front Nutr 2023;10:1154996. [Crossref] [PubMed]
32. Oz E, Aoudeh E, Murkovic M, et al. Heterocyclic aromatic amines in meat: Formation mechanisms, toxicological implications, occurrence, risk evaluation, and analytical methods. Meat Sci 2023;205:109312. [Crossref] [PubMed]
33. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 2023;402:203-34.
34. Riveros C, Al-Toubat M, Chalfant V, et al. The impact of socioeconomic status on the survival of men with early-onset prostate cancer. Am J Clin Exp Urol 2023;11:146-54.
35. Ling H, Sun K, Xia Q. Advances in precision treatment of urinary tumors in 2024. Journal of Urology for Clinicians (Electronic Version) 2025;73-80.
36. Chakrabarti D, Albertsen P, Adkins A, et al. The contemporary management of prostate cancer. CA Cancer J Clin 2025;75:552-86. [Crossref] [PubMed]
37. Morris MJ, Castellano D, Herrmann K, et al. (177)Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. Lancet 2024;404:1227-39. [Crossref] [PubMed]
38. Powles T, Valderrama BP, Gupta S, et al. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N Engl J Med 2024;390:875-88. [Crossref] [PubMed]
39. Suarez C, Rojas C, Shin SJ, et al. Novel pembrolizumab-based treatments as first-line therapy in advanced clear-cell renal cell carcinoma: substudy 03A of the open-label, umbrella platform, phase I/II KEYMAKER-U03 trial. Ann Oncol 2026;37:229-40. [Crossref] [PubMed]
40. Li C, Kuang X, Zou S, et al. Rising incidence and clinical impact of kidney cancer in China and worldwide: a call for targeted prevention, early diagnosis, and equitable treatment. Transl Androl Urol 2025;14:1391-407. [Crossref] [PubMed]
41. Sung H, Siegel RL, Rosenberg PS, et al. Emerging cancer trends among young adults in the USA: analysis of a population-based cancer registry. Lancet Public Health 2019;4:e137-47. [Crossref] [PubMed]
42. GBD 2021 Risk Factors Collaborators. Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 2024;403:2162-203. [Crossref] [PubMed]
43. Barry KH, Martinsen JI, Alavanja MCR, et al. Risk of early-onset prostate cancer associated with occupation in the Nordic countries. Eur J Cancer 2017;87:92-100. [Crossref] [PubMed]
44. Salinas CA, Tsodikov A, Ishak-Howard M, et al. Prostate cancer in young men: an important clinical entity. Nat Rev Urol 2014;11:317-23. [Crossref] [PubMed]
45. Hemminki K, Li X. Age-specific familial risks for renal cell carcinoma with evidence on recessive heritable effects. Kidney Int 2004;65:2298-302. [Crossref] [PubMed]
46. Beebe-Dimmer JL, Levin AM, Ray AM, et al. Chromosome 8q24 markers: risk of early-onset and familial prostate cancer. Int J Cancer 2008;122:2876-9. [Crossref] [PubMed]
47. Tang T, Tan X, Wang Z, et al. Germline Mutations in Patients With Early-Onset Prostate Cancer. Front Oncol 2022;12:826778. [Crossref] [PubMed]
48. Wu J, Wang H, Ricketts CJ, et al. Germline mutations of renal cancer predisposition genes and clinical relevance in Chinese patients with sporadic, early-onset disease. Cancer 2019;125:1060-9. [Crossref] [PubMed]
49. Mima K, Hamada T, Inamura K, et al. The microbiome and rise of early-onset cancers: knowledge gaps and research opportunities. Gut Microbes 2023;15:2269623. [Crossref] [PubMed]
50. Lawson JS, Glenn WK. Multiple pathogens and prostate cancer. Infect Agent Cancer 2022;17:23. [Crossref] [PubMed]
51. Sun JX, Xu JZ, Liu CQ, et al. The association between human papillomavirus and bladder cancer: Evidence from meta-analysis and two-sample mendelian randomization. J Med Virol 2023;95:e28208. [Crossref] [PubMed]
52. Caini S, Gandini S, Dudas M, et al. Sexually transmitted infections and prostate cancer risk: a systematic review and meta-analysis. Cancer Epidemiol 2014;38:329-38. [Crossref] [PubMed]
53. Wu K, Liu X, Wang Y, et al. Clinicopathological characteristics and outcomes of synchronous renal cell carcinoma and urothelial carcinoma: A population-based analysis. Front Public Health 2022;10:994351. [Crossref] [PubMed]
54. Lucca I, Klatte T, Fajkovic H, et al. Gender differences in incidence and outcomes of urothelial and kidney cancer. Nat Rev Urol 2015;12:653. [Crossref] [PubMed]
55. Dobruch J, Daneshmand S, Fisch M, et al. Gender and Bladder Cancer: A Collaborative Review of Etiology, Biology, and Outcomes. Eur Urol 2016;69:300-10. [Crossref] [PubMed]
56. Zhu S, Zhao H. Sexual dimorphism in bladder cancer: a review of etiology, biology, diagnosis, and outcomes. Front Pharmacol 2023;14:1326627. [Crossref] [PubMed]
57. Sundi D, Collier KA, Yang Y, et al. Roles of Androgen Receptor Signaling in Urothelial Carcinoma. Cancers (Basel) 2024;16:746. [Crossref] [PubMed]
58. Daugherty SE, Lacey JV Jr, Pfeiffer RM, et al. Reproductive factors and menopausal hormone therapy and bladder cancer risk in the NIH-AARP Diet and Health Study. Int J Cancer 2013;133:462-72. [Crossref] [PubMed]
59. Li CK, Dalvi R, Yonemori K, et al. Care of adolescents and young adults with cancer in Asia: results of an ESMO/SIOPE/SIOP Asia survey. ESMO Open 2019;4:e000467. [Crossref] [PubMed]
60. Siegel DA, O'Neil ME, Richards TB, et al. Prostate Cancer Incidence and Survival, by Stage and Race/Ethnicity - United States, 2001-2017. MMWR Morb Mortal Wkly Rep 2020;69:1473-80. [Crossref] [PubMed]
61. Bleyer A, Spreafico F, Barr R. Prostate cancer in young men: An emerging young adult and older adolescent challenge. Cancer 2020;126:46-57. [Crossref] [PubMed]