Cancer stands as one of the top three leading causes of death in the United States (US), second only to heart disease (1). As the US population ages, the burden of cancer on public health and, by extension, the economy will only increase. Among the different cancer types, genitourinary cancers have shown a steady increase in incidence, particularly in developed countries like the US, imposing a substantial burden in terms of morbidity, mortality, and health expenditures (2). Despite this prevalence and variability across factors like age, gender, race, ethnicity, and geography, there remains a poor understanding of the different outcomes in diverse patient groups. Previous studies have focused on individual cancer types such as prostate, bladder, and kidney cancer (3–5).

Recent advancements in surveillance methods and access to extensive datasets have allowed researchers to explore the temporal patterns of these cancers. For instance, a recent study utilized the Surveillance, Epidemiology, and End Results (SEER) to evaluate cross-sectional mortality rates, country-level geographic patterns, and short- and long-term temporal trends in the incidence and mortality of the four genitourinary cancers (prostate, bladder, kidney, and testes) (6).

Our study utilizes the Center for Disease Control and Prevention (CDC) WONDER database to investigate differences in the age-adjusted mortality rates (AAMRs) for these four genitourinary cancers based on sex, age, race, state, urban/rural residence, and region in the US from 1999 to 2020. By shedding light on these trends, we hope to empower decision-makers with targeted actions to reduce cancer-related fatalities. Furthermore, our work seeks to advocate for developing and sharing large-scale global databases to foster further research on genitourinary tumors.

Leveraging the nationwide CDC WONDER database, we observed temporal variations in genitourinary cancer mortality based on gender, race, and geography in the US from 1999 to 2020. The observed decline in the AAMRs of prostate, bladder, and kidney cancer may be attributable to the increased uptake of screening methods, such as serum prostate-specific antigen (PSA) levels and diagnostic imaging, and advances in the treatment of genitourinary cancers that have prolonged overall survival. Testicular cancer was an important exception, demonstrating a stable overall AAMR during the study period and a statistically significant increase in Whites. Nonetheless, relative to all genitourinary cancers, testicular cancer maintained the lowest AAMR and mortality burden, a testament to its favorable treatment response that leads to long-term survival in most patients (10).

The factors underpinning the disproportionate representation of Blacks/African Americans in prostate cancer incidence and mortality are still being studied. Individuals of African descent are more likely to harbor genetic variants associated with a higher risk of prostate cancer development (11). Studies have also indicated a potential racial bias in the US that puts Black men at higher risks of receiving inadequate treatment and having lower survival rates compared to White patients with prostate cancer (12–14).

The introduction of prostate cancer screening by PSA played a significant role in increasing the diagnoses of prostate cancer in its early stages during the 2000s and early 2010s, reflected in our findings as a declining mortality rate. The US Preventative Services Task Force’s (USPTF) recommendation to limit PSA-based screening in the early 2010s coincided with an increase in the incidence of advanced-stage prostate cancer (3, 15). Accordingly, we observed a rise or stabilization in overall prostate cancer AAMR after 2014, most notable among Black, White, and Asian/Pacific Islanders; American Indians/Alaskan Natives continued their steady decline. Even after the revised 2018 USPTF recommendation suggesting that high-risk individuals—namely Blacks/African Americans and those with a family history of prostate cancer—discuss the benefits and drawbacks of PSA-based screening to allow for shared decision-making, we did not observe a decline in prostate cancer AAMR in the Black/African American population.

Bladder cancer demonstrated a significantly higher AAMR in men compared to women, consistent with recent US data (2, 6). While smoking is a well-known risk factor for bladder cancer and is more prevalent among males, the higher incidence and mortality of bladder cancer in men compared to women in the US cannot be solely attributed to this factor (16, 17). Sex hormone effects on the bladder, sex-specific responses to carcinogens, and differential exposure of the urothelium to carcinogens have been suggested as additional factors behind this gender disparity (16). Regarding race, white individuals demonstrated a higher AAMR for bladder cancer as compared with other races, consistent with the higher incidence of bladder cancer in Whites (6). The reasons behind this are also poorly understood and cannot be fully explained by lifestyle differences like smoking, as it is more prevalent among Blacks/African Americans (18). However, a subset analysis assessing bladder cancer mortality rates between races stratified by gender demonstrated comparable mortality rates for bladder cancer between black and white women in the US despite black women having a 36% lower incidence of bladder cancer (19). To explain this, Black patients with muscle-invasive bladder cancer are less likely to receive optimal treatment and being black is also an independent risk factor for increased 90-day mortality for bladder cancer (19). These findings indicate a persisting racial bias in bladder cancer treatment and survival that must be addressed.

Kidney cancer is twice as common in men than in women (20). This was reflected in our study as a higher AAMR in males than in females. Females also demonstrate better survival outcomes from kidney cancer, and global data has reported a decrease in kidney cancer mortality in females by 11.3% between 1990 and 2013, while a 9.9% increase was observed in males (21). Our US-based data showed that AAMR decreased in both genders, with a steeper annual decline in females and a recent statistically non-significant increase in AAMR in males between 2018 and 2020. American Indian/Alaska Natives have the highest incidence of kidney cancer, perhaps due to a higher prevalence of risk factors such as smoking and higher BMI in this group (22). However, we observed the highest AAMRs of kidney cancer in White people. A recent study utilizing the CDC WONDER database to report disparities in kidney cancer AAMR between 1999 and 2020 also demonstrated the highest AAMR in White individuals. Still, American Indians/Alaska Natives initially had the highest AAMR in 1999 (5). This contrasts our findings, where White individuals displayed the highest AAMR throughout the study period. These discrepant results may be due to the CDC WONDER database being constantly updated, including additional records or corrections not present during the prior study.

The higher cancer mortality burden and a slower decline in genitourinary cancer-related mortality in rural versus urban communities are well documented (23). Our results showing a statistically significant increase in bladder cancer AAMR and a stable kidney cancer AAMR in rural populations are concerning and have recently been reproduced (23). Reasons for poorer cancer outcomes in rural areas include unequal access to cancer screening facilities, a failure to control lifestyle risk factors such as obesity and smoking, and poorer health literacy among rural residents (24). Cancer patients from rural communities are also more prone to missing appointments, having to travel longer distances to get treatment, being diagnosed at a later stage, being treated at smaller treatment facilities and not at specialist centers, and having fewer opportunities for enrollment into clinical trials as compared to urban neighborhoods, hence resulting in poorer outcomes (25).

On geographic disparities, our findings are consistent with a recent SEER database analysis demonstrating a higher prostate cancer mortality in Midwestern and Western states despite its relatively low incidence in these regions (6). This is unlikely to be because of inequalities in access to healthcare, as the Western states have some of the highest percentages of insurance coverage. While the incidence of kidney cancer is highest in Appalachia and other Southern states, we observed its mortality is highest in the Midwest (6). Although bladder cancer incidence is highest in the Northeast, widely believed to be due to arsenic contaminating water wells in this region (26), we observed the highest mortality of bladder cancer in the South. We also identified clusters of high mortality for specific genitourinary cancers in specific states. Importantly, Mokdad et al. (27) showed that clusters of high mortality existed for kidney, bladder, prostate, and testicular cancer in counties that may be masked when only looking at overall AMMR or at the level of the state. Potential explanations for these variations in mortality can be divided into distinct aspects of cancer epidemiology: a varying prevalence of risk factors (e.g., lifestyle factors such as obesity, diabetes and smoking, and genetic risk factors that negatively impact prognosis); different levels of success of public health screening and prevention policies; varying degrees of access to cancer treatment and structural factors like the healthcare infrastructure itself and insurance coverage; and different cancer treatment strategies (6, 28). The public health response to these findings should involve improving cancer screening opportunities for malignancies where screening benefits have been shown, controlling risk factors and comorbidities associated with genitourinary cancers, and improving access to the standard-of-care cancer therapies.

An examination of different data sources enriches our understanding of cancer epidemiology. A recent study by Schafer et al. (6) examined incidence and mortality trends of genitourinary cancers in the US, spanning a period similar to the present analysis. This study utilized the SEER database, a population-based nationwide database that offers detailed information on cancer incidence and survival and includes comprehensive historical and demographic data crucial for ascertaining temporal trends in cancer incidence and mortality (29). However, the SEER database covers only approximately 34% of the US population, potentially limiting the generalizability of its findings. Another database, the National Cancer Database (NCDB), contains data from hospital registries from Commission on Cancer-accredited facilities, capturing about 70% of the country’s newly diagnosed cancer cases (30). While the NCDB contains detailed clinical information that can be used to ascertain the quality of cancer treatment and response rates, this database is limited to CoC-accredited facilities and, therefore, may not be fully representative of cancer outcomes, especially across racial and ethnic minorities and those who do not have access to these facilities.

The SEER database is often the database of choice when assessing sociodemographic disparities in cancer incidence and mortality trends. We utilized the CDC-WONDER database, which, on the one hand, is easily accessible and provides comprehensive national coverage by incorporating mortality data from all US states and territories, but on the other hand, may not capture the same level of detail regarding cancer-specific mortality and sociodemographic data as the SEER database. However, our study utilizing the CDC WONDER database is the first direct comparison of different national databases, and our findings are largely concordant with the recent findings of Schafer et al., who utilized the SEER database (6).

The present study highlights several critical areas for future research. The increase in prostate cancer AAMR after the change in PSA-based screening guidelines particularly underscores the importance of informed decision-making on PSA-based screening, particularly in Black individuals, as well as the identification of more genetic variants and lifestyle factors that enable an individualized screening strategy (31). Interpreting PSA levels considering race may also offer valuable insights (32). Our study also advocates for adopting the American Urological Association’s PSA screening guidelines, which recommends routine screening of at-risk individuals beginning at age 40–45 years, as well as offering baseline screening and frequent screening intervals in all men starting at age 45 years (33). We reproduced rural–urban disparities in genitourinary cancer mortality, which have remained unchanged over the past two decades. We observed a discrepancy in genitourinary cancer mortality in different geographic regions of the United States, which was not concordant with incidence data reported from previous studies and required further studies to identify the root causes.

Our study’s strengths include utilizing a comprehensive, nationwide database over a two-decade period, which allowed us to assess changes in mortality in light of technological and treatment advancements and changing cancer screening guidelines. However, limitations include inaccuracies in reporting data, such as misclassification of gender, race, and cause of death from death certificates, which could mislead the mortality data for American Indian/Alaska Natives and Asian/Pacific Islanders because of their relatively low representation in national databases. We did not identify gender disparities in the AAMR of genitourinary cancers within the studied racial groups, nor did we address racial disparities regarding genitourinary cancer mortality in rural/non-metropolitan areas. Thirdly, we did not compare mortality trends between Hispanic and non-Hispanic ethnicities.

For future studies, improving the representation of varying races and ethnicities in cancer databases is essential to obtain a more accurate understanding of incidence and mortality trends. For example, American Indian/Alaskan Natives and Asian/Pacific Islanders currently exhibit the lowest incident genitourinary cancer capture rates in the National Cancer Database. In contrast, capture rates are highest among Whites (34). Moreover, our study period does not cover the COVID-19 pandemic, which significantly impacted cancer care and disproportionately affected the treatment of cancer patients belonging to racial minority groups and those in rural areas, as well as increased the prevalence of obesity in US adults (35). Therefore, we recommend that future studies document mortality trends during this period.

Our study provides insights into the temporal trends and disparities in the death rates from genitourinary cancers in the US. Over the past 2 decades, the significant decline in mortality rates of genitourinary cancers represents a tremendous advance. Still, we demonstrated considerable gender, racial, and geographic disparities in genitourinary cancer mortality rates that continue to exist today. Understanding the burden of risk factors contributing to genitourinary cancer incidence and mortality across diverse patient groups and geographic regions will be essential for devising effective public health policies to better these trends.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

Ethical approval was not required for the study involving humans in accordance with the local legislation and institutional requirements. Written informed consent to participate in this study was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and the institutional requirements.

YG: Writing – original draft, Validation, Supervision, Project administration, Methodology, Investigation, Data curation, Conceptualization. MAlg: Writing – review & editing, Writing – original draft, Supervision, Project administration, Methodology, Investigation, Data curation, Conceptualization. MS: Writing – original draft, Methodology, Investigation, Data curation, Conceptualization. ASh: Writing – review & editing, Supervision, Writing – original draft, Methodology, Investigation, Data curation, Conceptualization. BS: Validation, Project administration, Writing – review & editing, Writing – original draft, Supervision, Methodology, Investigation, Data curation, Conceptualization. TA: Writing – review & editing, Writing – original draft, Supervision, Project administration, Methodology, Investigation, Data curation, Conceptualization. AR: Writing – review & editing, Writing – original draft, Visualization, Investigation, Conceptualization. ASa: Writing – review & editing, Writing – original draft, Methodology, Investigation, Data curation, Conceptualization. MAla: Writing – original draft, Methodology, Investigation, Data curation, Conceptualization. WA: Writing – original draft, Investigation, Conceptualization. AO: Writing – original draft, Investigation, Conceptualization. SA: Writing – original draft, Investigation, Conceptualization. KS: Writing – original draft, Investigation. MAlK: Writing – original draft, Investigation. AhA: Writing – original draft, Project administration, Methodology, Investigation, Conceptualization. AbA: Writing – original draft, Supervision, Project administration, Methodology, Investigation, Conceptualization. BA: Writing – original draft, Supervision, Methodology, Investigation, Conceptualization. AAd: Writing – original draft, Methodology, Investigation, Conceptualization. LA: Writing – original draft, Investigation. AAA: Writing – original draft, Investigation, Data curation. ZM: Writing – review & editing, Writing – original draft, Supervision, Project administration, Methodology, Investigation, Data curation, Conceptualization.