Our analysis estimated that more than $6.5 billion were spent in 2021 to treat new and recurrent patients with bladder cancer in the USA, what is similar to a study published by Mariotto et al. [4] in 2019, that estimated the bladder cancer cost in the USA to be $7.54 billion. The model showed that the cost profile varied based on the stage of disease. Average costs for patients with metastatic disease were much higher than costs for those patients with NMIBC or MIBC. This was true for both newly diagnosed patients as well as those patients presenting with a recurrence or progression. These findings are in accordance with a previous study that evaluated the costs of bladder cancer care to Medicare [21].

The contributing factors to total costs also differed according to the stages: costs for NMIBC were mostly associated with diagnostic and surveillance procedures while for patients with metastatic disease major drivers of cost were treatment related. Patients with MIBC were positioned in between, with surgical procedures being a higher driver of costs in this population. The high impact of surveillance procedures and local treatment in the costs of NMIBC has been recognized for more than 20 years [6, 16, 22, 23] and, as our data confirmed, has not changed. Several studies have evaluated the cost-effectiveness of various treatment strategies to help guide clinicians and payers in the market [5, 15, 24, 25]. For example, intravesical maintenance therapy with BCG is a mainstay of NMIBC treatment, and recent evidence suggests that BCG maintenance should be prioritized for patients with high-risk disease, as they are more likely to progress [15]. The global BCG shortage that started in 2019 due to a reduction in pharmaceutical manufacturers has inadvertently led to this prioritization of high-risk patients for BCG therapy when shortages exist, as well as reductions in maintenance BCG [26, 27].

This model showed a higher average cost of treatment for patients with metastatic bladder cancer than that reported in some previous publications: while we found that the average cost to the system for stage IVB patients was almost $170,000, other publications have found this cost to be lower. Aly et al. [10] and Yeung et al. [5] found an average lifetime cost for patients with stage IV bladder cancer to be closer to $120,000 and $107,000 dollars, respectively, while Sloan et al. [21] estimated the cost to be close to $50,000 dollars for the first year of treatment. Possible explanations for these differences are the timing of the studies and the methods used, including differences in payers. All three studies [5, 10, 21] were performed before the use of immunooncology became standard of care in bladder cancer.

The financial impact of bladder cancer management is substantial and varies significantly by region, with the USA experiencing notably higher costs than other countries [28]. A pan-European analysis by Leal et al. highlighted that bladder cancer represents 5% of total healthcare cancer expenditures across Europe, with an average cost per patient of €6942 (equivalent to $7526 in May 2024) [28]. France reported the highest national average cost at €11,937 ($12,904) per patient [28], while Quignot’s research in Germany documented the annual costs of treating NMIBC at €9250 ($10,028) and MIBC at €17,893 ($19,400) [29]. Similarly, Cox’s study in the UK calculated the cost of NMIBC treatment at approximately £8735 ($11,750) per patient [30]. Our model’s projections for the USA substantially surpass these figures (Table 1), confirming a pronounced disparity in bladder cancer management costs between the USA and other countries.

The analysis of patients with recurrent bladder cancer, highlights that recurrence drives up the costs of bladder cancer to the healthcare system. Total costs to treat recurrence are more than 50% higher than those to treat primary disease in our model. Mossanen et al. [16] had called attention to this fact in 2019, when their study showed that progressive disease contributed to 81% and 92% of the overall 5 years cost for intermediate- and high-risk NMIBC. This increase in cost for recurrent disease is driven both by the increased likelihood of disease recurrence with higher stage at initial diagnosis and the increased likelihood of a recurrence being at a higher stage than initial diagnosis [2, 14, 16]. Additionally, patients with recurrent disease are treated more aggressively, further increasing costs [2, 14, 16].

Given the high rates of recurrence seen in clinical practice (51–66%) [7] and the higher cost of treating the disease as it progresses and/or recurs described here and elsewhere [14, 16], an unmet need exists for treatments that could create a durable response with higher rates of complete response, reducing the likelihood of or delaying progression/recurrence. Some promising new diagnostics and therapies being investigated include urinary biomarkers, genomic profiling, and new intravesical and immunotherapy combination protocols which have the potential to improve the care and outcomes of patients with bladder cancer [16, 31,32,33]. While new therapies for NMIBC and MIBC are likely to increase costs for non-metastatic bladder cancer, they may be cost effective if they could prevent or delay progression to metastatic disease for which outcomes are poor [2, 3].

This study has a number of limitations. First, the model included patients diagnosed in 2021 as well as those expected to experience a recurrence/relapse within the same year. However, it does not account for patients who were under surveillance without confirmed evidence of disease. Surveillance strategies are known to be costly and can significantly impact the overall cost of managing patients with bladder cancer [6]. This consideration is crucial for the interpretation of our findings and must be integrated into any examination of our data, given that it may lead to an underestimation of our overall cost projections. Most of the information used to build the clinical evolution, patterns of care, and outcomes of the model, were collected from a physician survey. While this approach provides direct insights from healthcare providers, it is inherently limited by the potential for recall bias [34]. This bias may affect the accuracy of the reported practices and outcomes, introducing a layer of uncertainty to our findings. Another critical limitation stems from our reliance on the Department of Veterans Affairs (VA) database [18] as the primary source of cost data. While the VA database offers a robust and publicly accessible resource and is largely used in economic analyses in the USA, it may not accurately reflect the broader national cost landscape. The VA’s unique pricing negotiations and federal subsidization afford it lower costs for services and medications, which may not be representative of costs encountered in private or other public healthcare systems across the USA. This discrepancy can lead to an underestimation of the actual costs associated with bladder cancer management on a national scale, as costs in other healthcare settings can vary widely based on regional, insurance, and provider network differences [35]. Despite our team conducting a thorough internal validation analysis, involving expert consultations and benchmarking our findings against existing literature, we acknowledge that the absence of external model validation represents a limitation of our study. And finally, the absence of sensitivity analysis in our economic model limits the robustness of our conclusions, as it prevents the assessment of how variations in key assumptions may impact the results [36].