A Framework for Addressing Health Disparities in Adult Neurogenic Lower Urinary Tract Dysfunction-Systematic Review and Neurogenic Bladder Research Group Recommendations.

The systematic review and workshop recommendations by the Neurogenic Bladder Research Group offer a comprehensive framework for evaluating health disparities in adult neurogenic lower urinary tract dysfunction (NLUTD). The study acknowledges the multifaceted nature of health, highlighting that medical care, though critical, is not the sole determinant of health outcomes. Social determinants of health significantly influence the disparities seen in NLUTD. This report calls for a shift in focus from traditional urologic care to a broader, more inclusive perspective that accounts for the complex interplay of social, economic, and health care factors in managing NLUTD.

The development of lateral flow devices for urinary biomarkers to assess kidney health.

Serum creatinine levels are insensitive to real-time changes in kidney function or injury. There is a growing interest in assessing kidney injury by measuring biomarkers in body fluid. From our previous studies, we identified and reported three urinary biomarkers namely Uromodulin (UMOD), Osteopontin (OPN), and Interleukin-9 (IL-9) to be associated with kidney health. The availability of a rapid point-of-care test for these urinary biomarkers will potentially accelerate its applicability and accessibility. In this study, we aimed to develop novel lateral flow device (LFD) for UMOD, OPN and IL-9. We tested paired antibodies using Enzyme Linked Immunosorbent Assay wherein we observed functionality only for UMOD and OPN and not for IL-9. A conjugation buffer pH of 7.8 and 8.5 was found suitable at a detection antibody concentration of 15 µg/mL for LFD development. The developed LFDs were found to quantitatively measure UMOD standard (LLOD of 80,000 pg/mL) and OPN standard (LLOD of 8600 pg/mL) respectively. The LFD was also able to measure human urinary UMOD and OPN with a percent CV of 12.12 and 5.23 respectively.

Epithelial development of the urinary collecting system in the human embryo.

The urinary collecting system (UCS) consists of organized ducts that collect urine from the nephrons and transport it to the ureter and bladder. Understanding the histogenesis of the UCS is critical. Thirty human embryos between the Carnegie stages (CS) 18 and 23 were selected from the Congenital Anomaly Research Center, Kyoto, Japan. Epithelia of the UCS, ureter, and bladder of each sample were randomly selected. Histological findings of the epithelia were analyzed according to the following criteria: type of epithelium, presence or absence of glycogen, percentage of migrated nuclei, percentage of cells in mitosis, and the surrounding mesenchyme. A thickened epithelium lining a narrow luminal cavity was observed in the pre-expanded pelvic specimens at CS18-CS23. At CS23, after pelvic expansion, the UCS showed a thin epithelium with a large luminal cavity mainly located on the early branches, whereas the epithelium covering the subsequent branches had medium thickness. Histological characteristics differed depending on the UCS part and sample stage. The degree of differentiation was evaluated, revealing that in CS18-CS23 pre-expanded pelvis specimens, the undifferentiated epithelium was found in the zeroth to third/fifth generation, whereas at CS23, after pelvic expansion, a differentiated epithelium covered the UCS zeroth to seventh generation. In a comparison of the urothelial epithelium between the UCS, ureter, and bladder, we found that urinary tract differentiation may be initiated in the bladder, followed by the ureter, UCS zeroth to seventh generations, and finally, UCS eighth to end generations. An understanding of the histogenesis of embryonic stage UCS can aid in the clinical management of congenital urinary tract defects and other diseases.

Deep learning prediction of renal anomalies for prenatal ultrasound diagnosis.

Deep learning algorithms have demonstrated remarkable potential in clinical diagnostics, particularly in the field of medical imaging. In this study, we investigated the application of deep learning models in early detection of fetal kidney anomalies. To provide an enhanced interpretation of those models' predictions, we proposed an adapted two-class representation and developed a multi-class model interpretation approach for problems with more than two labels and variable hierarchical grouping of labels. Additionally, we employed the explainable AI (XAI) visualization tools Grad-CAM and HiResCAM, to gain insights into model predictions and identify reasons for misclassifications. The study dataset consisted of 969 ultrasound images from unique patients; 646 control images and 323 cases of kidney anomalies, including 259 cases of unilateral urinary tract dilation and 64 cases of unilateral multicystic dysplastic kidney. The best performing model achieved a cross-validated area under the ROC curve of 91.28% ± 0.52%, with an overall accuracy of 84.03% ± 0.76%, sensitivity of 77.39% ± 1.99%, and specificity of 87.35% ± 1.28%. Our findings emphasize the potential of deep learning models in predicting kidney anomalies from limited prenatal ultrasound imagery. The proposed adaptations in model representation and interpretation represent a novel solution to multi-class prediction problems.

Kidney and urogenital abnormalities in Down syndrome: a meta-analysis.

BACKGROUND: Reviews on Down syndrome do not or only marginally address the issue of kidney and urogenital tract abnormalities, and lower urinary tract dysfunctions. Hence, we performed a meta-analysis of the literature.  METHODS: A literature search was undertaken in the Library of Medicine, Web of Science and Excerpta Medica. The search algorithm combined various keywords: (Down syndrome OR trisomy 21 OR mongolism) AND (kidney OR urinary tract OR bladder) AND (malformation OR dysfunction OR anomaly OR abnormality OR size). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was used. RESULTS: Eight case-control studies were retained for the final analysis. Three studies addressed the prevalence of kidney and urogenital tract abnormalities: an increased pooled relative risk of 5.49 (95%-CI: 1.78-16.93) was observed in Down syndrome. Penile malformations, obstructive malformations (including urethral valves), dilated urinary tract system, and kidney hypodysplasia were especially common. Three reports addressed the prevalence of lower urinary tract dysfunction: an increased pooled relative risk of 2.95 (95%-CI: 1.15-7.56) was observed. Finally, an autoptic study and an ultrasound study disclosed a reduced kidney size in Down syndrome. CONCLUSIONS: This meta-analysis indicates that abnormalities of the kidney and urogenital tract, lower urinary tract dysfunctions, and a reduced kidney size present with an increased frequency in individuals with Down syndrome.

The Role of Metabolomics and Microbiology in Urinary Tract Infection.

One of the common illnesses that affect women's physical and mental health is urinary tract infection (UTI). The disappointing results of empirical anti-infective treatment and the lengthy time required for urine bacterial culture are two issues. Antibiotic misuse is common, especially in females who experience recurrent UTI (rUTI). This leads to a higher prevalence of antibiotic resistance in the microorganisms that cause the infection. Antibiotic therapy will face major challenges in the future, prompting clinicians to update their practices. New testing techniques are making the potential association between the urogenital microbiota and UTIs increasingly apparent. Monitoring changes in female urinary tract (UT) microbiota, as well as metabolites, may be useful in exploring newer preventive treatments for UTIs. This review focuses on advances in urogenital microbiology and organismal metabolites relevant to the identification and handling of UTIs in an attempt to provide novel methods for the identification and management of infections of the UT. Particular attention is paid to the microbiota and metabolites in the patient's urine in relation to their role in supporting host health.

Surgery for pulmonary lesions in patients with a history of urinary tract transitional cell carcinoma.

BACKGROUND: There has been little information on the actual diagnosis of pulmonary lesions in patients with a history of urinary tract transitional cell carcinoma (TCC) and short- and long- outcomes of pulmonary resection for these patients. METHODS: In the present study, the data of 37 consecutive patients with a history of TCC who underwent pulmonary resection for solitary pulmonary lesions were reviewed, and the clinical factors and short- and long-term outcomes were analyzed. RESULTS: The study population included 35 male patients, and 2 female patients. The mean age was 72.5 years. Twenty patients (80%) were smokers and showed a high incidence of chronic obstructive pulmonary disease. Pulmonary lesions and primary TCC were detected simultaneously in 5 patients and metachronously in 32 patients. The median interval between treatment for primary TCC and the detection of pulmonary lesion was 43 months. The mean tumor diameter was 23 mm. The types of resection included lobectomy (n = 19), segmentectomy (n = 8), and partial resection (n = 10). Twelve of 37 patients (32%) developed postoperative complications. The pathological diagnoses included primary lung cancer (n = 28), pulmonary metastasis from TCC (n = 7), and others (n = 2). The 5-year overall survival rate for all patients was 72%. The 5-year overall survival rate of patients with primary lung cancer was 74%, while that of patients with pulmonary metastasis from TCC was 57%. CONCLUSIONS: Surgery can be proactively considered for treating pulmonary lesions in patients with a previous history of TCC, as it provides favorable long-term outcomes.

Surgical procedure and recurrence of upper urinary tract stone: a national-wide study based on hospitalized patients.

PURPOSE: This study aimed to investigate the influence of surgical intervention on recurrence risk of upper urinary tract stone and compare the medical burden of various surgical procedures. METHODS: This study analyzed data from patients with upper urinary tract stone extracted from a national database of hospitalized patients in China, from January 2013 to December 2018. Surgical recurrence was defined as patients experience surgical procedures for upper urinary tract stone again with a time interval over 90 days. Associations of surgical procedures with surgical recurrence were evaluated by Cox regression. RESULTS: In total, 556,217 patients with upper urinary tract stone were included in the present analysis. The mean age of the population was 49.9 ± 13.1 years and 64.1% were men. During a median follow-up of 2.7 years (IQR 1.5-4.0 years), 23,012 patients (4.1%) had surgical recurrence with an incidence rate of 14.9 per 1000 person-years. Compared to patients receiving open surgery, ESWL (HR, 1.59; 95% CI 1.49-1.70), URS (HR, 1.38; 95% CI 1.31-1.45), and PCNL (HR, 1.11; 95% CI 1.06-1.18) showed a greater risk for surgical recurrence. Patients receiving ESWL had the shortest hospital stay length and the lowest cost among the 4 procedures. CONCLUSIONS: Compared with open surgery, ESWL, URS, and PCNL are associated with higher risks of surgical recurrence for upper urinary tract stone, while ESWL showed the least medical burden including both expenditure and hospital stay length. How to keep balance of intervention efficacy and medical expenditure is an important issue to be weighed cautiously in clinic practice and studied more in the future.

Renal toxicity of ifosfamide in children with cancer: an exploratory study integrating aldehyde dehydrogenase enzymatic activity data and a wide-array urinary metabolomics approach.

BACKGROUND: Ifosfamide is a major anti-cancer drug in children with well-known renal toxicity. Understanding the mechanisms underlying this toxicity could help identify children at increased risk of toxicity. METHODS: The IFOS01 study included children undergoing ifosfamide-based chemotherapy for Ewing sarcoma or rhabdomyosarcoma. A fully evaluation of renal function was performed during and after chemotherapy. Proton nuclear magnetic resonance (NMR) and conventional biochemistry were used to detect early signs of ifosfamide-induced tubulopathy. The enzymatic activity of aldehyde dehydrogenase (ALDH) was measured in the peripheral blood lymphocytes as a marker of ifosfamide-derived chloroacetaldehyde detoxification capacity. Plasma and urine concentrations of ifosfamide and dechloroethylated metabolites were quantified. RESULTS: The 15 participants received a median total ifosfamide dose of 59 g/m2 (range: 24-102), given over a median of 7 cycles (range: 4-14). All children had acute proximal tubular toxicity during chemotherapy that was reversible post-cycle, seen with both conventional assays and NMR. After a median follow-up of 31 months, 8/13 children presented overall chronic toxicity among which 7 had decreased glomerular filtration rate. ALDH enzymatic activity showed high inter- and intra-individual variations across cycles, though overall activity looked lower in children who subsequently developed chronic nephrotoxicity. Concentrations of ifosfamide and metabolites were similar in all children. CONCLUSIONS: Acute renal toxicity was frequent during chemotherapy and did not allow identification of children at risk for long-term toxicity. A role of ALDH in late renal dysfunction is possible so further exploration of its enzymatic activity and polymorphism should be encouraged to improve the understanding of ifosfamide-induced nephrotoxicity.

Impact of timing of urinary drainage on clinical outcomes in patients with obstructive pyelonephritis associated with upper urinary tract stones: a propensity score-matched analysis.

OBJECTIVE: We aimed to assess the impact of the timing of urinary drainage on clinical outcomes in patients with obstructive pyelonephritis (OPN) associated with upper urinary tract (UUT) stones. METHODS: We retrospectively evaluated the multicenter dataset of 240 patients with OPN associated with UUT stones who underwent urinary drainage. We divided the patients into two groups depending on the timing of urinary drainage; emergency drainage, defined as within 12 h from admission, and delayed drainage, defined as between 12 and 48 h from admission. The outcomes were the length of hospital stay, time to leukocyte normalization, and time to body temperature normalization. One-to-two propensity score matching (PSM) was applied to minimize the effect of confounders between the two groups. Subsequently, predictive patient factors for emergency drainage were analyzed using the logistic regression model. RESULTS: Only the time from admission to normal body temperature was significantly shorter in the emergency drainage group when compared with the delayed drainage group (median: 2 vs. 3 days; p = 0.02), while there was no difference in time from drainage to body temperature normalization between the two groups. On multivariable analysis, high pretreatment C-reactive protein (CRP) was associated with implementing emergency drainage within 12 h. CONCLUSIONS: The timing of urinary drainage was only associated with the duration of high fever, but it did not affect the postdrainage course. Emergency urinary drainage is more likely to be performed in severe patients, such as high pretreatment CRP.

Primary Health Care nurses' role in treating Lower Urinary Tract Dysfunction.

OBJECTIVE: To understand Primary Health Care nurses' role in treating Lower Urinary Tract Dysfunction. METHOD: Cross-sectional multi-methodological research, composed of quantitative and qualitative steps, independently and sequentially. Data collected remotely, through a questionnaire and focus group, analyzed using descriptive statistics and thematic analysis by Braun and Clarke, respectively. The project was approved under Opinion 22691119.0.0000.0030. RESULTS: A total of 145 nurses participated in the study in the quantitative step and 20 in the qualitative step, working in Primary Health Care in Brazil. Of the 93.1% nurses who reported having already cared for people with Urinary Tract Dysfunction, only 54.4% provided guidance, mainly for training the pelvic floor muscles. CONCLUSION: Even though they have legal support and access to demand, nurses do not have the knowledge to offer conservative treatment for Lower Urinary Tract Dysfunction. Despite this, they were motivated to do so as long as they received specific training.

Relationship Between Availability of Urologists and Primary Care Providers and Stage of Diagnosis for Invasive Urinary Bladder Cancer.

INTRODUCTION: With no recommended screening approach, urinary bladder cancer patients rely on referral to urologists to ensure timely diagnosis of bladder cancer. This requires coordination between primary and specialty care. We provide estimates of the relative association between primary care physician and urologist density on stage of urinary bladder cancer diagnosis. METHODS: We used 2010 to 2016 Pennsylvania Cancer Registry data to identify all adult patients diagnosed with bladder cancer. Our primary outcome was locoregional stage of diagnosis, since treatment modality changes and prognosis worsens beyond this stage. Based on patient's residential location at the time of diagnosis we defined both density of urologists and number of primary care providers (defined as providers per population) within the patient's county. We used univariate and multivariate logistic regression to estimate the association between provider density and likelihood of locoregional stage of diagnosis. We also controlled for age, sex, race/ethnicity, insurance type, and year. RESULTS: Our sample included 11,771 urinary bladder cancer patients with 10,607 diagnosed at locoregional stage and 1164 at distant stage. Multivariate regression results show primary care density was associated with significantly higher odds of locoregional stage of diagnosis (odds ratio of 1.05 [95% CI: 1.02-1.08]) while urologist density was associated with significantly lower odds of locoregional stage (odds ratio of 0.65 [95% CI: 0.48-0.89]). CONCLUSIONS: We found primary care density but not urologist density was associated with earlier stage of diagnosis, highlighting the importance of access to primary care and need for timely referral to urologic care.

Urinary catheter placement and adverse urinary outcomes with a focus on elevated risk in men with indwelling Foley catheters.

BACKGROUND: Prior studies indicated a link between urinary catheter use and urinary complications, highlighting the need for comprehensive, gender-specific investigations. This study explored the association through a national retrospective cohort, emphasizing gender disparities and long-term outcomes. METHODS: Our study utilized data from the entire population covered by Taiwan's National Health Insurance Research Database from 2000 to 2017. We included 148,304 patients who had undergone Foley catheter placement and their propensity-scores matched controls in the study. We evaluated urinary complications, which encompassed urinary tract cancer, urolithiasis, urethral stricture, obstructive uropathy, reflux uropathy, fistula, diverticulum, caruncle, false passage, prolapsed urethral mucosa, urinary tract rupture, and urinary tract infection. These were assessed using the Fine and Gray sub-distribution proportional hazards model to compare between the Foley and non-Foley groups. Sensitivity analyses were conducted with different matching ratios. RESULTS: In the study, the non-Foley group presented a marginally higher mean age (75.24 ± 10.47 years) than the Foley group (74.09 ± 10.47 years). The mean duration of Foley catheterization was 6.1 ± 4.19 years. Men with Foley catheterization exhibited the highest adjusted sub-distribution hazard ratios for urinary tract cancer (6.57, 95% CI: 5.85-7.37), followed by women with Foley catheterization (4.48, 95% CI: 3.98-5.05), and men without catheterization (1.58, 95% CI: 1.39-1.8) in comparison with women without the procedure. Furthermore, men with Foley catheterization were found to be at the greatest risk for complications such as urolithiasis, urethral stricture, obstructive and reflux uropathy, fistula, diverticulum, caruncle, false passage, prolapsed urethral mucosa, and urinary tract rupture. Conversely, women with urinary catheterization were most susceptible to urinary tract infections. CONCLUSIONS: The evidence confirms that urinary catheterization significantly increases urinary complications, particularly among men. Our study underscores the crucial need for healthcare providers to carefully evaluate the necessity of catheterization, aim to shorten its duration whenever feasible, and strictly adhere to established protocols to minimize complications.

Utility of The Paris System (TPS) for upper urinary tract cytopathology: correlation with histology follow-up and UroVysion fluorescence in situ hybridization (FISH) analysis.

INTRODUCTION: The Paris System (TPS) provides a uniform reporting system of urine cytology based on well-defined cytologic criteria. Due to their rarity, there are limited data on the utility of TPS in upper urinary tract (UUT) lesions and follow-up histology of cases with abnormal cytology. We aimed to evaluate the utility of TPS for UUT lesions by correlating the cytologic diagnoses using TPS criteria with subsequent histology. Additionally, the diagnostic utility of UroVysion (Abbott) fluorescence in situ hybridization (FISH) was assessed. MATERIALS AND METHODS: A total of 148 UUT cytology specimens were retrospectively identified (2018-2022). Cytologic interpretation was performed using TPS, and then correlated with the findings of concurrent or subsequent histologic specimens. The performance of UroVysion FISH was analyzed. Sensitivity and specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting high-grade urothelial carcinoma (HGUC) were determined. RESULTS: Among 83 patients who had concurrent or subsequent histologic specimens, cyto-histologic discrepancy was seen in 7 cases (8.4%). The sensitivity, specificity, PPV, and NPV using TPS criteria for detecting HGUC were 87%, and 92%, 96.4%, and 73%, respectively. UroVysion FISH was performed in 21 patients with atypical cytologic findings. The sensitivity and specificity of UroVysion for detecting HGUC was 75% and 86%, respectively, while PPV and NPV were 86% and 75%, respectively. CONCLUSIONS: In our experience, the application of TPS criteria for reporting upper urinary cytology was reliable at detecting UUT lesions, especially HGUC. UroVysion FISH was a valuable ancillary test for detecting HGUC of UUT.

Retzius-sparing vs. posterior urethral suspension: similar early-phase post-robotic radical prostatectomy continence outcomes.

Stress urinary incontinence (SUI) is a risk of robotic-assisted radical prostatectomy (RP) which can be a frustrating problem for both surgeons and patients. We aim to compare short-term continence outcomes between patients undergoing Retzius Sparing RP (RS-RP) and those undergoing standard RP with the inclusion of a PUS suture technique and suprapubic tube (PUS-RP). A retrospective review of 105 consecutive patients who underwent RP was performed, comparing patients who underwent RS-RP and PUS-RP. Our main outcome was pad usage as a surrogate for SUI. Patients were evaluated 4 weeks following RP and again at approximately 3 months. Continence was defined as no pad usage or up to one safety pad per day. Risk factors associated with not being continent were identified using univariate and multivariate analyses. In our cohort, 52 patients underwent RS-RP and 53 patients underwent PUS-RP. The two groups had similar patient demographics. Although not statistically significant, there was a higher rate of a positive surgical margin in the RS-RP compared to PUS-RP (25% vs 15%, p = 0.204). At one month follow-up for PUS-RP and RS-RP, there was no significant difference in the frequency of continent men (69.2% vs. 76.9%, p = 0.302). At 3-month follow-up for the two groups of patients, again, there was no significant difference in the frequency of continence for PUS-RP and RS-RP (86.2% vs 88%, p = 0.824). Patients who underwent RS-RP had similar rates of continence to those patients undergoing PUS-RP in the short-term post-operative period.

Frequency of Treatment Failure of UTIs in Children With Congenital Urinary Tract Anomalies.

OBJECTIVES: Children with certain congenital anomalies of the kidney and urinary tract and neurogenic bladder (CAKUT/NGB) are at higher risk of treatment failure for urinary tract infections (UTIs) than children with normal genitourinary anatomy, but the literature describing treatment and outcomes is limited. The objectives of this study were to describe the rate of treatment failure in children with CAKUT/NGB and compare duration of antibiotics between those with and without treatment failure. METHODS: Multicenter retrospective cohort of children 0 to 17 years old with CAKUT/NGB who presented to the emergency department with fever or hypothermia and were diagnosed with UTI between 2017 and 2018. The outcome of interest was treatment failure, defined as subsequent emergency department visit or hospitalization for UTI because of the same pathogen within 30 days of the index encounter. Descriptive statistics and univariates analyses were used to compare covariates between groups. RESULTS: Of the 2014 patient encounters identified, 482 were included. Twenty-nine (6.0%) of the 482 included encounters had treatment failure. There was no difference in the mean duration of intravenous antibiotics (3.4 ± 2.5 days, 3.5 ± 2.8 days, P = .87) or total antibiotics between children with and without treatment failure (10.2 ± 3.8 days, 10.8 ± 4.0 days, P = .39) Of note, there was a higher rate of bacteremia in children with treatment failure (P = .04). CONCLUSIONS: In children with CAKUT/NGB and UTI, 6.0% of encounters had treatment failure. Duration of antibiotics was not associated with treatment failure. Larger studies are needed to assess whether bacteremia modifies the risk of treatment failure.

Association of Androgen Receptor and PD-L1 Expression in Upper Urinary Tract Urothelial Carcinoma.

BACKGROUND/AIM: The response to immune checkpoint inhibitors (ICIs) or enfortumab vedotin is limited in patients with upper urinary tract urothelial carcinoma (UTUC), and the development of new targeted therapy for UTUC is eagerly needed. Several biomarkers, including programmed cell death-ligand 1 (PD-L1), have already been reported as predictors of response to ICIs therapy for UTUC. Recently, several studies have shown that steroid hormone receptors, including the androgen receptor (AR), are associated with progression of urothelial carcinoma. MATERIALS AND METHODS: We prepared tissue microarrays (TMA) from paraffin blocks of UTUC specimens in 99 non-metastatic UTUC patients who underwent radical nephroureterectomy. With these TMA sections, we performed immunohistochemical staining for PD-L1 and AR and examined PD-L1 and AR expression levels in tumor cells. In addition, we analyzed the correlation between these markers and clinical prognosis in UTUC cases. RESULTS: PD-L1 was positive in 24 (24%) of the 99 samples, whereas AR was positive in 20 (20%) patients. AR-negative samples had significantly higher PD-L1 expression level than that the AR-positive samples (mean value 4.70% versus 2.55%, p=0.0324). Among AR-positive cases, patients with absence of PD-L1 expression had significantly lower cancer-specific survival (CSS) than that in PD-L1 expression-positive cases (p=0.049), although PD-L1 expression had no significant impact on CSS in AR-negative cases (p=0.920). CONCLUSION: Our findings suggest that AR is the promising target for UTUC treatment, especially in PD-L1-negative cases.

One Size Fits Some: Approaching Rare Malignancies of the Urinary Tract.

OPINION STATEMENT: Urothelial carcinoma is the predominant cancer of the urinary tract but when divergent and subtype histology (non-urothelial) are identified at time of pathologic diagnosis, therapeutic and diagnostic challenges transpire. To this end, pathologic review to confirm any non-urothelial histology is key since these subtypes can often be overlooked. Few prospective trials are dedicated to understanding these non-urothelial histologic types; however, current, and past trials did allow patients with these non-urothelial histologic types to enroll, and inferences can be made about treatment efficacy and survival. Existing treatment regimens for non-urothelial bladder cancers are akin to standard urothelial cancer regimens using surgical approaches for localized disease and platinum-based chemotherapy for advanced disease. The reported clinical trials, that will be discussed, center on non-urothelial histologic types. These studies, albeit limited, provide critical insight into tumor biology and response to standard platinum-based chemotherapy, immune checkpoint inhibitors, and antibody drug conjugates. The inclusion of non-urothelial histologic types will be essential for clinical trials in development to provide further therapeutic advances and provide essential efficacy data.