This study used GBD 2021 data to characterize long-term trends in BC incidence, mortality, YLLs, YLDs, and DALYs in the U.S. from 1980 to 2021. At the national level, age-standardized incidence rates gradually declined beginning in the late 2010s, accompanied by a more modest decrease in age-standardized mortality rates. These improvements likely reflect advances in preventive strategies, evolving treatment strategies, and broader access to specialized care. However, national averages obscure substantial heterogeneity at the state level. While several Northeastern states experienced pronounced declines in both incidence and mortality-particularly among men-other states, including West Virginia, Kentucky, Delaware, and Nevada, showed persistently elevated or plateauing trends. Among states with consistently extreme values, Maine exhibited the highest age-standardized incidence rates throughout most of the study period, albeit with recent declines, whereas Hawaii consistently reported the lowest incidence and mortality rates Supporting Files. These contrasts likely reflect regional differences in environmental exposures, healthcare access, and the effectiveness of public health interventions.

Despite having one of the highest per-capita healthcare expenditures globally (49), the U.S. continues to report comparatively high age-standardized incidence rates of BC relative to many high-income and high-SDI regions, consistent with prior reports (3). This pattern likely reflects the country’s advanced diagnostic capacity and widespread use of cystoscopy and imaging, which facilitate more complete case ascertainment rather than a true excess in underlying disease risk (50–52). At the same time, this discrepancy highlights a potential imbalance in healthcare priorities, with disproportionate emphasis on diagnosis and treatment relative to prevention and risk reduction (53). The persistently high incidence is particularly concerning given evidence that up to 80% of BC cases diagnosed over the past two decades may be attributable to preventable exposures (54), whereas inherited genetic factors account for only a small proportion of cases in Western populations (55). Together, these findings underscore the importance of strengthening prevention-oriented public health strategies, including smoking cessation, occupational safety, and mitigation of environmental carcinogen exposure (56).

Age-specific analyses revealed a consistent increase in BC incidence, mortality, and DALYs with advancing age across all states, in line with prior literature (3). Although age-specific patterns remained largely stable over time, data from 2021 demonstrated particularly high incidence and mortality rates in the 75-80+ age groups in several populous states, including California, Texas, and Connecticut Supporting Files. This trend likely reflects demographic aging, as the U.S. population aged 65 years and older increased by 38.6% between 2010 and 2020 (56). In addition, recent evidence suggests that the oldest adults-especially men aged 85 years and older-have not experienced the same improvements in cancer mortality as younger seniors, with the largest relative increases observed in individuals aged 75-79 years and 80 years or older (57). These findings indicate that, despite overall progress, the burden of BC among older adults remains a significant public health challenge.

Consistent with prior studies, our analysis confirms that men experience BC burden rates approximately four times higher than women (15). Age-period analyses across states revealed broadly similar age-related trajectories in both sexes, characterized by a sharp rise after age 60; however, women consistently exhibited lower absolute rates and a slower decline in mortality over time. Previous studies have shown that women are more likely to present with advanced disease and have poorer survival outcomes (16,58,59). One contributing factor may be delayed evaluation of hematuria in women, as symptoms are more frequently attributed to urinary tract infections or gynecologic conditions (58,60). Addressing these disparities will require improved adherence to updated clinical guidelines, including the 2025 American Urological Association recommendations (61), alongside the incorporation of validated biomarkers for risk stratification and the adoption of sex-aware diagnostic pathways, which account for different presentations and burden rates in both genders in primary care settings.

Beyond healthcare delivery factors, emerging evidence points to biological mechanisms underlying sex-based disparities in BC. Differences in immune surveillance, hormonal milieu, hormone receptor signaling, and genetic or epigenetic alterations have been implicated (62). For example, androgen signaling may promote oncogenic pathways in men, whereas sex-specific immune responses may influence tumor behavior and progression in women (63,64). Importantly, these differences persist even after adjustment for known exposures such as smoking and occupational hazards (65). Ongoing research into sex hormones, immune checkpoints, and tumor genomics may help clarify why men are disproportionately affected by BC and why women experience worse outcomes once diagnosed.

Geographic heterogeneity observed in this study align with previous reports demonstrating the highest BC incidence among men and in Northeastern states, including Maine, New Hampshire, and Vermont (10). Current evidence has been unable to explain these patterns by factoring for smoking alone (66), which indicates that other public health factors are involved in these disparities. Environmental carcinogens, particularly arsenic contamination of drinking water from private domestic wells, have been implicated in elevated incidence in New England (66,67). Recent declines in incidence in some Northeastern states may reflect improvements in water treatment and broader public health interventions (68). For example, professionally installed and maintained household arsenic treatment systems in Maine and New Jersey have achieved substantial reductions in exposure and associated cancer risk (69), although incomplete effectiveness in a subset of systems highlights the need for continued monitoring and maintenance. Regulatory actions, such as New Hampshire’s adoption of a stricter arsenic standard for public drinking water in 2021 (70), represent important steps toward long-term risk reduction, although the long latency of BC means that benefits may take decades to fully emerge. However, interstate comparisons within the Northeast should be interpreted cautiously. States such as New York differ substantially from more rural neighboring states in terms of population density, reliance on private domestic wells, and patterns of environmental exposure, which may partially explain observed differences in temporal trends independent of policy effectiveness.

In contrast, several states in the South and West exhibit disproportionately high BC mortality despite more moderate incidence. Nevada and Southern states such as West Virginia, Kentucky, and Alabama demonstrated some of the highest age-standardized mortality rates, consistent with prior studies (13,71). Elevated mortality in these regions may reflect higher smoking-attributable cancer burdens (72), greater rurality (73,74), and reduced access to timely diagnostic and treatment services (74,75). Lower insurance coverage and longer travel distances to specialized care centers may further contribute to delayed diagnosis and worse outcomes (76). By contrast, the Northeast’s relatively low uninsured rates (77) may partially explain why states in this region experience high incidence but comparatively lower mortality, resulting in a clear regional mismatch between disease occurrence and survival.

Hawaii represents a notable outlier, with consistently low BC incidence and mortality. Several factors likely contribute to this favorable profile, including a predominantly Asian and Pacific Islander population, which has historically lower BC risk compared with non-Hispanic White populations (78), low adult smoking prevalence (79), and strong tobacco control policies (80). In addition, industrial and environmental carcinogen exposures are generally less prevalent, and access to healthcare and insurance coverage is relatively high (81). Together, these demographic, behavioral, and structural factors likely explain Hawaii’s consistently low BC burden, underscoring the potential impact of comprehensive prevention and access-to-care strategies.

The strengths of this study include the use of robust, population-based estimates to examine long-term temporal trends and state-level disparities in BC burden across the U.S. Nevertheless, our findings must be interpreted within the context of the study design. GBD estimates rely on modeled data due to incomplete or heterogeneous primary data sources, which may introduce uncertainty, particularly in states with sparse reporting. Although advanced statistical methods are used to mitigate these limitations, some degree of imprecision is unavoidable. Additionally, the inherent lag in GBD data availability means that trends beyond 2021 are not captured. Finally, this analysis is primarily descriptive and does not directly evaluate individual-level risk factors or clinical characteristics, limiting causal inference regarding the drivers of observed patterns. Most of the trends reported in this study are age-standardized; therefore, discrepancies with surveillance systems that report crude or partially adjusted rates, such as some Centers for Disease Control and Prevention (CDC) summaries, likely reflect methodological differences rather than true epidemiological disagreement. Notably, Nevada remained among the states with persistently elevated mortality trends even after age standardization.