1. Introduction

The human body harbors complex microbial communities at multiple anatomical sites; these site-specific communities are collectively referred to as “microbiomes.” ¹ These microbial communities contribute to local ecological balance and host homeostasis. In 1683, Anthonie van Leeuwenhoek first described small “animalcules” in dental plaque, providing one of the earliest observations of microorganisms in the human body ². Since then, major microbiomes have been identified in the skin, oral cavity, gut, and respiratory tract, with more recent studies demonstrating the presence of a resident microbiome in the urinary tract. For many years, urine and the bladder were considered sterile, with the presence of microbes in urine being attributed to contamination from the external genital tract or sampling errors. This view was disputed by early sequencing studies using 16S ribosomal RNA (rRNA) gene surveys beginning around 2010, which hinted at bacterial DNA in voided urine from healthy people, even though these works were not initially recognized as definitive evidence of a resident urinary microbiome ^3-5. Standard urine culture techniques developed in the mid-20th century only grow fast-growing uropathogens but fail to detect common fastidious organisms that are present in lower numbers in an uninfected “disease-free” bladder ⁶.

The mere presence of some species within specific microbiomes greatly increases the risk of certain cancers, such as head and neck squamous cell carcinoma in the presence of viruses like Epstein–Barr virus and human papillomavirus, and gastric cancer in Helicobacter pylori colonizers ^7-9. Bladder cancer is the ninth most common cancer in the world and amongst the top 10 most common cancers in the United States, with 18 cases projected to be diagnosed per 100,000 people per year ^{10, 11}. There is a noticeable disparity in incidence and treatment outcomes between men and women, with men being diagnosed nearly three times more commonly and women experiencing poorer outcomes after diagnosis ^12,13. Risk factors for bladder cancer include, but are not limited to, age (preponderance in older adults), sex (more common in males), smoking history, family history, exposure to aniline dyes, chemotherapy, radiation, presence of indwelling catheters, and schistosomiasis ^14-17. Given the heterogeneity of the affected population, diverse risk factors, and low likelihood of cancer in asymptomatic individuals, screening is not recommended ¹⁸.

This review aims to consolidate current literature on the role of the urinary microbiome in bladder carcinogenesis and in disease behavior among patients with established bladder cancer. We also highlight current knowledge gaps and unresolved questions in the literature.

2. Methods

A comprehensive literature search was performed to identify studies evaluating the role of the urinary microbiome in bladder cancer. Electronic databases, including PubMed, Scopus, and Web of Science, were searched from inception through December 2025 using combinations of the terms “urinary microbiome,” “urine microbiome,” “bladder microbiota,” “bladder cancer,” “urothelial carcinoma,” and “16S rRNA sequencing.” Only peer-reviewed human studies published in English were included in this narrative review. Eligible studies comprised observational cohorts, case–control studies, and clinical trials that characterized urinary microbial composition using microbiome-characterization methods such as 16S rRNA gene sequencing, metagenomic sequencing, and expanded quantitative urine culture. Reviews, editorials, animal-only studies, and case reports without microbiome profiling were excluded.

3. Urinary microbiome

3.1. Sampling

Because the gastrointestinal, skin, genital tract, and lower urinary tract microbiota overlap substantially, sampling methods strongly influence data interpretation. Samples can be collected by a clean catch of mid-stream urine, transurethral catheterization (TUC), or suprapubic aspiration (SPA). Studies conducted in women showed good concordance between samples collected by TUC and SPA from the same individual, allowing for the substitution of the more uncomfortable and invasive SPA with TUC. Voided samples, such as those collected by mid-stream catch, showed a higher representation of both pathogenic and fastidious bacteria that are commonly present on the skin or in the vulvovaginal tract ⁵. Urethral swabbing and first-catch voided urine specimens showed similar distribution of bacterial genera and their proportions, eliminating the need for invasive sampling ¹⁹.

3.2. Composition

The first studies that overturned the long-held belief that urine from healthy individuals was sterile came in the early 2010s when culture-independent molecular methods were applied to study the composition of urine. In a landmark 2012 study, Wolfe et al. ⁵ used 16S rRNA gene sequencing and metaproteomics to detect and characterize bacterial DNA in the urine collected from asymptomatic adults by various sampling methods, showing that healthy urine contains diverse bacterial communities that standard culture misses because most of these microbes are low in abundance or fastidious]. The study used standard urine culturing techniques, light microscopy, and 16S rRNA gene sequencing to compare urine samples from 12 asymptomatic adult women and 11 culture-negative participants with urodynamic diseases to assess differences in urinary microbial growth. Discrepancies were also noted between growth on standard cultures and DNA obtained from 16S rRNA gene sequencing on urine from the same individual, even when sampled by different techniques, which demonstrates the high sensitivity of standard urine cultures to uropathogens but poor ability to isolate other commensal species with lower biomass ⁵.

The composition of the urinary microbiome appears to be influenced by several factors. Several studies have evaluated variation in microbial composition according to age, sex, urological conditions, urodynamic dysfunction, and catheter use.^XX Several studies have evaluated variation in microbial composition according to age ^{19, 20, 21}, sex ^{22, 23, 24}, urological conditions, urodynamic dysfunction ^{22, 23}, and catheter use ²².

3.2.1. Composition in healthy, asymptomatic individuals

The urinary microbiome of healthy, asymptomatic individuals is characterized by a complex mix of bacterial genera, with notable variability across sex and age. Studies have demonstrated a more diverse mix of genera among female participants compared to their male counterparts, with female samples having an average of 21 genera compared to 11.5 genera in males ⁶. Sex-related differences in urinary microbial composition have also been reported. The healthy female urinary microbiome has an abundance of Lactobacillus species, whereas a healthy male urinary microbiome is dominated by Corynebacterium, Streptococcus, and Staphylococcus species ^{22, 23, 24}. Several additional taxa also appear to show sex-associated distribution patterns, such as Actinobacteria and Bacteroidetes being common in females but being infrequent in male samples ^{3,22, 25}. Genera such as Prevotella, Veillonella, and Aerococcus are a part of the core urinary microbiome for both men and women, with varying degrees of representation likely influenced by other factors ²².

The urinary microbiome also varies with age. Female participants generally exhibit a greater number of detected genera than male participants, with no significant difference noted in the number of genera in premenopausal and postmenopausal women. Lactobacillus is more common in premenopausal women, and Mobiluncus in postmenopausal women ¹⁹. The decrease in Lactobacillus in postmenopausal women is perhaps better explained by vaginal atrophy and a decrease in estrogen with menopause, which could alter the urothelial and vaginal epithelium, influencing this change ²⁰. Genera like Streptococcus were noted to increase in older men, whereas the abundance of Gardnerella and Acinetobacter decreased relatively with age in both genders ²¹. Because bladder cancer primarily affects older adults, age-related changes in the urinary microbiome are particularly relevant to understanding its development and progression.

It is unclear how significantly the microbiome changes with race and geographical regions, as most studies were either done using small sample sizes or heterogeneous populations. Studies from China and Nigeria that had patient populations belonging to a single ethnicity and geographical region showed a core urinary microbiome markedly different from that typically seen in studies from the United States or other heterogeneous studies ^{21, 26}. These differences may reflect geographic variation in the urinary microbiome related to diet, environment, and lifestyle.

3.2.2. Impact of risk factors on the urinary microbiome

Smoking is a major risk factor for the development of bladder cancer. In a study comparing healthy men with men with bladder cancer, the effect of smoking on the urinary microbiome in healthy individuals was not significant ²⁷. However, there was a change in the composition of the microbiome, with Bacteroidaceae, Erysipelotrichales, Lachnospiraceae, and Bacteroides being higher in smokers than non-smokers. These findings suggest that tobacco exposure may contribute to urinary dysbiosis ²⁷. Genera like Sphingomonas, Acinetobacter, and Micrococcus have the ability to break down polycyclic aromatic hydrocarbons (PAH), a known carcinogen associated with cigarette smoke. Other PAH metabolizers, such as Enterobacter and Ralstonia, are also abundant in the urine of those with bladder cancer. The ability to metabolize PAH allows these species to dominate the urinary microbiome of smokers and would likely explain an increased presence in smokers or those with bladder cancer ²⁸. However, these associations remain largely correlative. While smoking is an established causal risk factor for bladder cancer, it may independently alter both bladder cancer risk and urinary microbial composition, with enrichment of PAH-metabolizing bacteria representing a secondary ecological effect rather than a direct contributor to carcinogenesis. Additionally, tumor development itself may alter the bladder microenvironment through changes in inflammation, nutrient availability, or epithelial integrity, thereby selecting for microbial taxa capable of metabolizing environmental carcinogens. Further studies are needed to determine whether these microbial shifts contribute directly to carcinogenesis or simply reflect smoking-related and tumor-related ecological change.

A study based in Nigeria demonstrated a unique microbial profile within the urine of individuals infected with Schistosoma haematobium when compared to uninfected individuals ²⁶. Veillonellaceae, Fusobacteriaceae, Lactobacillaceae, and Enterococcaceae were present in significantly higher concentrations in infected cases, while Oxalobacteraceae, Enterobacteriaceae, and Staphylococcaceae were significantly elevated in the urinary microbiome of healthy individuals]. At the time this review was conducted, no studies relating the urinary microbiome to arsenic exposure in humans could be found.

3.2.3. Chronic infections and lower urinary tract symptoms

Studies have shown that patients with neurogenic bladder tend to have greater proportions of members of Enterobacteriaceae ^{22, 23}. This finding was consistent irrespective of gender. Lactobacillus crispatus, which is found in abundance in healthy, asymptomatic women, was notably absent among cultivated colonies in females with neurogenic bladders]. Males with neurogenic bladder were also found to have lower numbers of Corynebacterium species, which is otherwise a common genus in healthy asymptomatic males ²².

In a large, nested case-control study, Sutcliffe et al. ²⁹ demonstrated a positive association between a history of gonorrhea and lower urinary tract symptoms (LUTS) such as urinary retention, increased frequency, and urgency in men]. Extending this study, Michaud et al. ³⁰ performed a large prospective study that demonstrated a nearly two-fold increase in bladder cancer risk in men with gonorrhea compared to men with no history of it ^29,30. Other studies have demonstrated a clear variance in species in the urinary microbiome of those with LUTS and sexually transmitted infections, with organisms such as Prevotella and Sneathia species being almost unique to these individuals ^9,25. Taking all this information into account, the causal contribution of these factors to carcinogenesis remains unclear. It is possible that gonorrhea and other sexually transmitted infections can increase chronic inflammatory conditions of the bladder or urodynamic disease, causing urinary retention that in turn increases the risk of urinary tract infections (UTIs). This microbiome change could plausibly contribute to the persistence of UTIs due to an interplay between the microbiome species and uropathogens, assist in antibiotic resistance, or directly contribute to chronic inflammation of the bladder, thereby creating a pro-inflammatory environment that may favor carcinogenesis.

3.3. Association with bladder cancer

3.3.1. Potential mechanisms of carcinogenesis

While mechanisms such as chronic inflammation, disruption of epithelial barrier integrity, immune modulation, and production of carcinogenic metabolites have been extensively studied in other microbiome-associated malignancies, emerging evidence suggests that similar pathways may contribute to bladder cancer development.Persistent colonization by uropathogens can induce chronic inflammation within the bladder microenvironment. Activation of pattern recognition receptors such as Toll-like receptors on urothelial cells leads to downstream signaling through pathways including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), resulting in production of pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha. Chronic inflammatory signaling promotes cellular proliferation, oxidative stress, and DNA damage, all of which may facilitate tumor initiation and progression ^{31, 32}. Fusobacterium nucleatum, which has been identified in urinary microbiome studies, promotes tumor-associated inflammation through activation of NF-κB pathways and has been implicated in multiple epithelial cancers ^{33, 34}.

Microbial metabolism can generate reactive oxygen species, reactive nitrogen species, and nitrosamines, all of which can induce DNA mutations and genomic instability. Escherichia coli strains harbor the pks genomic island, which encodes colibactin, a genotoxin capable of inducing DNA double-strand breaks ³⁵. In addition, bacterial enzymes, such as β-glucuronidases produced by bacteria belonging to Clostridium spp. and Escherichia coli, may influence the metabolism of environmental carcinogens excreted in urine, potentially increasing local exposure of urothelial cells to activated carcinogenic compounds. These metabolic interactions may be particularly relevant in the bladder, where urine serves as a reservoir for xenobiotic metabolites derived from smoking and occupational exposures ³⁶.The bladder urothelium normally functions as a protective barrier, preventing microbial adherence and invasion. However, certain bacterial species can disrupt epithelial integrity through the production of toxins, proteases, and other virulence factors that impair tight junctions and epithelial adhesion molecules. Uropathogenic Escherichia coli, for example, produces toxins such as hemolysin that disrupt epithelial cells and facilitate bacterial invasion. Loss of epithelial barrier function may increase mucosal permeability, facilitate microbial invasion, and enhance inflammatory responses. Persistent epithelial injury and regenerative proliferation may contribute to malignant transformation over time. ³⁷

The microbiome may also influence antitumor immunity within the bladder. Microbial components and metabolites can shape the local immune landscape by altering dendritic cell activation, T-cell differentiation, and cytokine production. These effects may impact immune surveillance and tumor progression.

3.3.2. Signature urotypes in bladder cancer

Several studies have tried to establish a “urotype” associated with bladder cancer and have reported heterogeneous microbial profiles. The common theme seems to be a notable depletion in the dominant commensal in both men and women, which could have been protective in healthy adults ³⁸. The phyla Firmicutes and Bacteroidetes were most represented in patients with bladder cancer, followed by Proteobacteria and Actinobacteria, making up 98.53% of the total microbiota. The most frequent genera were Bacteroides, Escherichia–Shigella, Staphylococcus, and Enterococcus, representing 31.99% of the total microbiota ³⁹. Smokers with bladder cancer often have an increased representation of Bacteroidaceae, Erysipelotrichales, and Lachnospiraceae ²⁷. The bladder microbiome also appears to vary according to muscle-invasiveness status, an important prognostic feature in bladder cancer. Anoxybacillus, Massilia, Thermomonas, Brachybacterium, Micrococcus, Nocardioides, Larkinella, Jeotgalibacillus, and Geomicrobium were found to be increased in the urine of those with recurrent non–muscle-invasive bladder cancer (NMIBC), potentially making their detection a surveillance tool for treatment response. Haemophilus, Veillonella, Bacteroides, and Faecalibacterium genera were more abundant in the urine of muscle-invasive bladder cancer patients ^{38, 40}. Studies have also shown differences between the urinary microbiome and tumor tissue microbiome, with a significant difference in microbiome composition of urine and mucosal tissue sampling on beta diversity analysis ⁴¹. This finding may reflect niche-selection by tumor-associated metabolites or site-specific microbial adaptation, although mechanistic inference remains premature ⁴².

3.3.3. Lactobacillus as a protective agent against bladder carcinogenesis

Lactobacillus plays a key role in suppressing uropathogens and promoting immune surveillance through the generation of organic acids, hydrogen peroxide, and bacteriocins. Lactobacillus crispatus, which is a dominant commensal in healthy women and men, effectively inhibited the growth of Proteus by exerting an antibacterial effect through acidification of urine and biofilm inhibition ⁴³. In women, vaginal Lactobacillus spp. may inhibit Neisseria gonorrheae epithelial interactions, suggesting a possible protective role against gonococcal colonization, which may reduce the risk of chronic LUTS ⁴⁴. Loss of this organism and other commensals with age, hormonal imbalance, frequent antibiotic use, or their suppression by other uropathogens, causing dysbiosis in chronic UTIs and LUTS, may favor persistent inflammation, epithelial damage, and immune dysfunction, thereby promoting a microenvironment that may favor tumorigenesis and immune evasion.

3.4. Effect on and variability with treatment

The urinary microbiome appears to influence the way chemotherapeutic agents are metabolized in the bladder, affecting treatment outcomes ⁴⁵. Antibiotic-induced dysbiosis, chronic UTIs along with the secondary metabolites they produce, and the presence of urodynamic diseases, may all result in an increased risk of carcinogenesis in the bladder ⁴⁶.

3.4.1. Bacillus Calmette–Guérin

The influence of the urinary microbiome is evident in response to intravesical Bacillus Calmette–Guérin (BCG), which remains the cornerstone of treatment for NMIBC. BCG efficacy relies on robust innate immune activation and recruitment of neutrophils, macrophages, and T cells. A favorable urinary microbiome, characterized by higher microbial diversity and increased abundance of Lactobacillus, appears to amplify these immune responses, whereas alterations in the urinary microbiome may blunt immune activation or promote immune tolerance, contributing to BCG failure and disease recurrence ⁴⁷.

Serratia, Brochothrix, Negativicoccus, Escherichia–Shigella, and Pseudomonas are more common in the urine microbiomes of BCG responders compared to those who did not respond to BCG ⁴⁰. Proteobacteria were common in patients undergoing BCG therapy who had a recurrence of NMIBC. The presence of Lactobacillus was once again protective, as it was more abundant in patients without recurrence ⁴⁸.

3.4.2. Immune checkpoint inhibitors

Microbiome and immune system interactions may represent a critical and previously underrecognized determinant of immunotherapy responsiveness in bladder cancer. In particular, the microbiome has been proposed as a key biological contributor to heterogeneity in clinical responses to both intravesical BCG and immune checkpoint inhibitors (ICIs), beyond tumor-intrinsic factors such as programmed death-ligand 1 (PD-L1) expression or mutational burden ⁴⁹. Increasing evidence supports a role for both the gut and urinary microbiota in modulating antitumor immune responses in bladder cancer ⁵⁰. Associations between urinary microbial composition and immune checkpoint regulation support the functional relevance of urinary dysbiosis in cases of bladder cancer ⁵¹.

The gut microbiome provides the strongest existing evidence for microbiome-mediated modulation of ICI responsiveness. High microbial diversity and production of immunologically active metabolites, particularly short-chain fatty acids (SCFAs) such as butyrate and propionate, enhance systemic antitumor immune responses by promoting dendritic cell maturation, increasing cytotoxic CD8⁺ T-cell function, and supporting effector cytokine production required for effective programmed cell death protein 1 (PD-1)/PD-L1 blockade ^{50, 52}. These metabolites exert their effects through epigenetic regulation, G-protein–coupled receptor signaling, and modulation of T-cell exhaustion pathways, directly influencing antitumor immunity ^{50, 52}. This well-described interaction between the gut microbiome and the immune system provides a useful framework for understanding how the urinary microbiome may similarly influence immune responses within the bladder tumor microenvironment. Urinary microbes can interact directly with urothelial and immune cells through pattern-recognition receptors, including Toll-like receptors and nucleotide-binding and oligomerization domain-like receptors, leading to changes in cytokine signaling, antigen presentation, and immune cell recruitment ⁴⁷. When microbial signaling is balanced, these interactions support effective innate immune activation; however, its disruption may promote chronic inflammation that favors immune suppression and reduced responsiveness to ICIs ⁵⁰.

Converging evidence links microbial dysbiosis to both immune checkpoint pathway regulation and clinical outcomes in bladder cancer. In male patients with NMIBC, PD-L1-positive tumors exhibited significantly higher urinary microbial diversity compared to PD-L1-negative tumors, with a dose-response relationship observed that, as the number of PD-L1-positive cells increased, urinary microbial richness also increased ⁵¹.

Importantly, antibiotic-induced disruption of this microbial-immune axis translates directly to worse clinical outcomes in patients receiving ICIs. In patients with muscle-invasive bladder cancer treated with neoadjuvant pembrolizumab, antibiotic use was associated with lower pathologic complete response rates (15% vs. 50%) and worse 24-month relapse-free survival (63% vs. 90%), with fluoroquinolones showing particularly poor outcomes ⁵³. These findings demonstrate that a healthy, diverse microbiome is essential for optimal ICI responsiveness, and its disruption by antibiotics, whether affecting gut or urinary microbial communities, impairs the antitumor immune responses necessary for effective PD-1/PD-L1 blockade.

This integrated understanding raises several critical questions for future investigation, including whether baseline urinary or gut microbiome profiling can identify patients with microbial signatures predictive of both PD-L1 expression and ICI responsiveness. Furthermore, the potential for microbiome restoration strategies, such as fecal microbiota transplantation or targeted probiotics, to rescue ICI responsiveness in patients requiring antibiotics warrants investigation. Finally, these findings raise the question of whether antibiotic stewardship protocols should be specifically tailored for patients planned for or currently receiving immunotherapy.

4. Diagnostic/prognostic use of microbiome studies/clinical trials in progress

Intravesical instillations of Lactobacillus species have been researched as an alternative to BCG for the treatment of bladder cancer in animal models with success, with a reduction in pro-inflammatory state ⁵⁴. Accurate assessment of the microbial profile of the urine, especially in those with more than one unmodifiable risk factor, can help track any changes in the microbiome, perhaps even using it as an early sign of a developing tumor microenvironment. Exploring microbial deficiencies in specific urotypes will allow us to specifically replenish the urine microbiome in an attempt to restore “eubiosis.”

Given the significant overlap between the urogenital and colonic microbiomes, it would be interesting to observe any influence that changes in the stool microbiome have on the urinary microbiome. If there is significant bacterial translocation through the bloodstream or interstitium between the two systems, rather than a passive contiguous spread of microbes, one could attempt to target urine eubiosis through nutritional interventions that would then heal gut dysbiosis. Another option would be fecal microbiota transfer from healthy individuals to those with bladder cancer. This could also be attempted to treat chronic LUTS or recurrent UTIs if they are found in the future to be purely driven by urinary dysbiosis.

Due consideration should also be given to antibiotic use, which can kill beneficial commensals. Narrowing the antibiotics to specifically target uropathogens and spare commensals can help prevent antibiotic-induced dysbiosis, which can take months to heal. Organisms that are slow metabolizers or inhibit local degradation of chemotherapeutic agents can be used as intravesical adjuvants, potentially leading to a decrease in systemic side effects due to the lower dose of antineoplastic agents being used in this scenario. In contrast, fast metabolizer species can be used as adjuvants in patients receiving toxic chemotherapeutic or other medical regimens that can concentrate in the bladder, leading to cystitis, in an attempt to reduce toxicity. Clinical trials and prospective studies are needed on this subject to better determine the feasibility of these ideas.

5. Currently active clinical trials exploring the role of the urinary microbiome in bladder cancer

Currently active clinical trials exploring the role of urinary microbiome in bladder cancer are summarized in Table 1. There are currently five active clinical trials exploring the role of urinary microbiome in patients with bladder cancer, of which three are currently recruiting patients. The studies are primarily aiming to evaluate whether certain microbial signatures predict response to BCG and chemotherapy, predict risk of relapse, and overall prognosis. Also, some studies are trying to create a local urinary microbiome registry that may facilitate the development of more personalized therapeutic strategies for patients with bladder cancer in the future.

6. Conclusion

There is growing evidence associating alterations in the urinary microbial ecosystem with bladder cancer. Across multiple studies, patients with bladder cancer demonstrate consistent shifts in urinary bacterial communities, including loss of potentially protective organisms such as Lactobacillus and enrichment of taxa like Fusobacterium, Prevotella, Acinetobacter, and Streptococcus, organisms known to drive inflammation or alter epithelial biology in other cancers. These patterns are not random; instead, they cluster into recognizable community types that appear to correlate with tumor presence, recurrence risk, and even response to intravesical therapies.

While very intriguing, we are just beginning to understand this association and possible causation. Most existing studies are small, cross-sectional, and methodologically heterogeneous, differing in urine collection techniques, sequencing platforms, and contamination controls. Antibiotic use can substantially alter microbiome composition, diversity, and resilience, and many studies used only a short antibiotic washout period for their participants. Because urine is a low-biomass sample, even minor technical differences can dramatically influence results, which likely explains why no single microbial signature has yet emerged as “definitive.” While there is little doubt that there is a urinary microbiome, it still remains unclear whether its alteration contributes to malignant transformation or simply reflects changes in the bladder microenvironment created by the tumor itself.

Currently active clinical trials are trying to answer some of these questions. Knowing the prognostic significance of the microbial profile and having a local registry will pave the way for personalized bladder cancer treatment, including treatments to positively modify the urinary microbiome, improving outcomes in bladder cancer patients. If found to predict risk of recurrence, altering the urinary microbiome could be a safe and cost-effective solution to prevent recurrence of bladder cancer. It will also be very interesting to see if we can change the urinary microbiome to reduce the risk of bladder cancer in patients at risk. Urinary microbiome profiles could become powerful non-invasive biomarkers for early detection, risk stratification, and surveillance.

In short, bladder cancer can no longer be viewed purely as a disease of malignant urothelial cells. It appears to exist within a dynamic microbial ecosystem that may influence its initiation, progression, and treatment response. Understanding this ecosystem is not merely an academic exercise; it has the potential to fundamentally change how we screen, treat, and ultimately prevent bladder cancer.