Bladder cancer incidence trends in the US from 1992–2019

Urothelial bladder cancer epidemiology

Urothelial bladder cancer is in the top ten cancers in the US and worldwide, representing a ≈3% of all cancer-related deaths (1). Although bladder cancer mortality has been declining in recent decades, incidence remains steady with only modest reductions; This may be explained by factors including reduced smoking prevalence, greater access to healthcare, novel therapies, and longer life expectancy (2). Despite this favorable trend in incidence, globally bladder cancer represents a significant cause of morbidity and mortality, with an estimated ~1M new cases and ~397,000 deaths projected for 2040 (3). Moreover, the treatment and control of bladder cancer represent a significant economic burden (4). In the US, similar trends have been anticipated, however, when these trends are disaggregated, certain geographic locations in the country have seen opposite trends with higher incidence rates compared to the average nationwide (5). Thus, the scarcity of granular and harmonized trend data is still needed.

Disease trajectories are not only essential for resource allocation, but for guiding screening efforts and health policies. The recent study ‘Long-term Trends in Bladder Cancer Incidence Using a Harmonized Staging Variable: A SEER-Based Study’, published in Cancer Epidemiology, Biomarkers and Prevention, demonstrated that using an updated and harmonized staging provides clearer and smoother trends in bladder cancer incidence compared to older systems, showing a consistent 4% annual decrease in bladder cancer Tis (in situ) cases since 1992. By discussing the findings on this paper, here I aim to foster a constructive dialogue among authors and the broader scientific community by highlighting findings that emerged during the review while revisiting the epidemiology in bladder cancer.

Various risk factors are known to increase the risk of bladder cancer; for instance, this disease is more frequent in non-Hispanic White men (male-to-female ratio of 3.5 to 1), smokers, and people aged ≥65 years. Other risk factors include occupational exposures to aromatic amines in industries such as rubber, leather, and paint manufacturing. Furthermore, persistent urinary tract infections and arsenic in drinking water, have also been associated with higher risk of bladder cancer (6). Although more stringent controls exist to mitigate these risk factors, some still persist (7). More recently germline variation has been shown to confer a minimal but statistically significant risk with genes involved in xenobiotics metabolism (8).

In bladder cancer onset, the disease remains confined to the mucosa for long periods of time. In 48% of cases the cancer is diagnosed when localized to the primary site, while in 35% at localized stage, 7% are diagnosed with regional spread, and 5% are diagnosed with distant metastasis; the remaining cases (5%) are unclassified (9,10). This stage distribution contributes to an overall 5-year relative survival rate of 71% for all stages combined. Although survival is high, this is stage-dependent, with rates of 97% when disease is in situ, and decreasing to 71% when localized, 39% for regional, and 8% for distant metastatic disease (11); these figures underscore the critical importance of early detection and effective management of non-muscle-invasive disease to prevent progression. Moreover, notable disparities in bladder cancer exist. Mortality rates are slightly higher in Black men and women than in White, despite their lower incidence, this suggests differences in access to care, tumor aggressiveness, or comorbidities (12).

The Surveillance, Epidemiology, and End Results (SEER) database

After the National Cancer Act was passed by the U.S. Congress in 1971, the National Cancer Program was created, aiming to improve cancer research, prevention, diagnosis, and treatment. In 1973, the SEER Program was created to systematically collect cancer data, as a comprehensive cancer surveillance system (13). By systematically accumulating and analyzing data on patient demographics, tumor characteristics, and treatment, it has been possible to elucidate trends in cancer epidemiology and guide preventive efforts. Due to advancements in disease classification and stratification, the introduction of a harmonized database incorporating standardized definitions of bladder cancer staging, aligned with the American Joint Committee on Cancer (AJCC) 8^th edition allows comparative analyses of incidence trends throughout the years. However, the varying staging systems between 1992 and 2019 make it challenging to directly compare them and gain insights into disease trends. Currently, SEER provides different tier-access databases (i.e., SEER Research Plus), serving as a powerful resource for conducting longitudinal studies on cancer trajectories.

In the current work, Kumar and colleagues (14) leverage from restricted-access SEER data to evaluate the implications of staging harmonization on bladder cancer epidemiology over time. Periodically, AJCC updates its staging manuals, which can make comparing historical data difficult. This is expected to keep changing while enhanced methods allow to stratify and personalize care in bladder cancer. The SEER Program aims to optimize current and historic trends by employing complex algorithms to update historical staging data like Tumor size, Node involvement, and Metastasis (TNM) and align them with modern definitions. SEER developed the harmonized definition used in this work to establish a consistent standard for analyzing long-term trends in incidence. The revisions used in the paper involved ‘long-’ and ’short-term’ (i.e., 1992+ and 2004+, respectively) staging fields that are consistent over time permitting a more reliable analysis of stage distribution, survival, and trends from the early 1990s to date (15).

Restaging bladder cancer

Kumar and colleagues (14) harmonized the staging definition for bladder cancer based on the AJCC 8^th edition (Bladder Chapter) on 176,234 cases diagnosed between 1992 and 2019 using data from the SEER 12 registry. The latest AJCC edition serves as a consistent staging base for reclassifying bladder cancer cases. The authors employed a mapping algorithm to retrieve extent of disease (EOD) codes and derive the consistent TNM stages. The EOD data collection system provides detailed clinical and pathological information about the disease status at diagnosis. This process allowed for the establishment of a standard definition for the T, N, and M variables for the long-term trend analysis. Overall, 9% of cases were reclassified for T stage, with the highest reclassification occurring in the earliest period [1992–2003]. Reclassification generally involved shifts within muscle-invasive bladder cancer (MIBC) or non-muscle-invasive bladder cancer (NMIBC) stages, with minimal movement between these two groups, except for a small number of cases in 2016–2017 period. The proposed restaging had minimal to no impact when recategorizing invasiveness, thus, it is unlikely that restaging will have clinical implications for management and care of MIBC. In 1992–2003 major changes occurred among Tis, Ta (non-invasive), T1 (invading connective tissue), T2 (growing into muscle), and T3 (growing through muscle into the perivesical fat tissue) stages, and the proportion of TX cases decreased. Whereas for 2004–2015, 2016–2017, and 2018–2019 periods a negligible amount was defined as TX; moreover, the vast majority of these cases already had metastatic disease at diagnosis. For N stage, 11% of cases were reclassified, primarily due to recoding NX cases as N0 (no regional lymph nodes), leading to a marked reduction in NX under the revised system. For M stage, reclassification was modest (2%). Most changes involved recoding MX cases to M0, eliminating MX classifications entirely, which is relevant in the clinical management of patients with metastasis. According to the original staging system, Tis case incidence rose from 1992 to 2006 [annual percent change (APC) 3.2%] and then declined (APC −4.8%). On the contrary, the revised system showed a consistent annual decline of 4% since 1992.

Challenges analyzing trends

A key challenge when analyzing long-term trends in bladder cancer is the constant evolution of its staging classification systems since 1992. Since 1920s methods to stage and classify bladder cancer have been employed; in the sixties the Jewett-Strong-Marshall system was widely adopted, however, in 1983 (16) the more popular staging system used in the clinic was established, the TNM classification, replacing all previous systems (17).

These systems have progressively refined tumor (T) staging and lymph node (N) assessment; for instance, the AJCC 6^th edition introduced a more granular N classification, while the 7^th edition prioritized the number and location of positive nodes over their size. The introduction of a dedicated metastasis (M) field in 2004 further improved specificity. The algorithmic mapping employed by Kumar and colleagues (14) necessitates a harmonized definition for primary sites and histology over time, ensuring comparability across cases since 1992, despite adaptations in EOD coding in alignment with evolving AJCC standards. The implementation of two temporal frameworks for the SEER Staging Over Time (SOT) adjusted variables—1992 forward for ‘long-term’ trends and—2004 forward for ’short-term’ trends, addressed the systematic discrepancies in staging data collection methodologies prior to and post-2004; Nevertheless, changes in classification are not expected to change the effective disease burden.

A caveat in the current work (14), as suggested by the authors, was the comparison of the original and revised trends, while in SEER website it is mentioned (15) that using different staging systems in the same analysis is not recommended (may introduce bias), it is unclear how readers should interpret the difference observed between revised and original trends. Thus, caution must exist given that differences may arise from mere reclassification rather than real epidemiologic changes. Although this study represents an opportunity to examine incidence trends at the TNM level, the numbers remained closely similar, except when calculating APC, where the authors found a statistically significant decreasing trend of T2 and T3 cases after 2003 (APC −2.3%). More importantly, this refinement process had a minimal impact on the fundamental clinical distinction between MIBC and NMIBC, with only 50 of 176,234 cases changing between categories. The minimal change between these categories is explained due to a more intricate pathological profile compared to limited disease. These finding confirm that, overall, observed trends for MIBC and NMIBC may persist independent of staging revisions.

A strength in this work is that data completeness improved under the revised system, with fewer cases having an unknown N stage and M stage now determined for all cases; suggesting this may be a better strategy to preserve sample size during data analysis without assuming imputed data. As Kumar and colleagues acknowledged, although undetermined/unknown stages reduced with the revised staging system, it remains constrained by the original data collected at diagnosis in those years. Moreover, the ascertainment of histology and nodal positivity data likely changed in recent years, and authors had to make assumptions without possibly testing them or conducting appropriate sensitivity analyses.

Lastly, while the authors completed a thorough TNM analysis, future work could benefit from disaggregated trend analyses by geographic location and demographic factors such as age, sex, and race/ethnicity. Such granular investigations would strengthen the epidemiological insights and generate additional hypotheses for future research. This study highlights the importance of using consistent, long-term staging variables for trend analysis in bladder cancer, yet disaggregated data is still very much needed. The authors make an interesting case that these refinements could unveil hidden patterns. While the modest scale of reclassification suggests trends would likely remain comparable to the original data, there are genuine advantages to the revised system: it produces clearer, more interpretable incidence patterns over time. These findings also aligned with reported trends in other regions (18), which is reassuring. Moreover, this harmonization approach should also be applied to other cancer types to better assess the impact of restaging. Together, they confirm an overall decline in US bladder cancer incidence. Moving forward, it would be valuable to thoughtfully assess the clinical and policy benefits of this resource-intensive restaging approach. I hope this commentary will support and inspire future studies that strengthen cancer trend analysis and help translate these insights into impactful public health interventions and clinical improvements.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Cancer Epidemiology. The article has undergone external peer review.

Peer Review File: Available at https://ace.amegroups.com/article/view/10.21037/ace-2026-1-0007/prf

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://ace.amegroups.com/article/view/10.21037/ace-2026-1-0007/coif). The author has no conflicts of interest to declare.

Ethical Statement: The author is 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.

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