HER2 expression in upper tract urothelial carcinoma and the relationship with clinicopathological characteristics-an analysis of 155 patients in Southwest China.

OBJECTIVE: We aimed to evaluate the expression of HER2 in patients with upper tract urothelial carcinoma (UTUC) in Southwest China by using a relatively large cohort, and to determine the relationship between HER2 expression and clinicopathological characters. MATERIALS AND METHODS: We retrospectively enrolled the clinical data of 155 UTUC patients who have undergone radical nephroureterectomy (RNU) from March 2019 to September 2022. HER2 expression was assessed using immunohistochemistry and scored according to the HercepTest (Scores of 0 or 1 + were considered as negative and 2 + or 3 + as positive). Tumor molecular phenotype was classified by the panel of CK20, CK5/6, and CD44. RESULTS: HER2 was overexpressed in 55 (35.5%) patients. It was associated with pathologic characteristics such as grade (p = 0.017), tumor molecular phenotype (p < 0.001) and Ki-67 expression (p = 0.017). On univariate and multivariable logistic regression analysis, HER2 overexpression remained associated with higher grade (HR, 10.6; 95% CI 1.0-112.6; p = 0.050) and luminal molecular phenotype (HR, 8.0; 95% CI 1,6-38.4; p = 0.010). During disease progression after nephroureterectomy, the phenotype of the tumor might change and a switch phenomenon in phenotype after recurrence in the bladder was reported. CONCLUSION: According to our study, in Southwest China, one-third of UTUC patients overexpressed HER2. Tumors with high grade or luminal phenotype tended to be HER2 positive. HER2 may represent a promising target for therapy in UTUC.

Narrative review of value frameworks in urothelial carcinoma and positioning of enfortumab vedotin.

AIMS: Evaluate existing oncology value frameworks in terms of their methodology, structure, characteristics, and functionality using the example of enfortumab vedotin, an approved therapy for urothelial carcinoma. METHODS: A search of PubMed, grey literature, and official websites of relevant international organizations was performed from January 2022 to March 2023. RESULTS: Six frameworks were identified and analyzed, including the American Society of Clinical Oncology's assessment framework, European Society for Medical Oncology's Magnitude of Clinical Benefit Scale, the National Comprehensive Cancer Network's Evidence Blocks, Memorial Sloan Kettering Cancer Center's DrugAbacus, Institute for Clinical and Economic Review's assessment framework, and the Drug Assessment Framework. Comparisons across frameworks were challenging, owing to differing approaches, objectives, perspectives, methodology, and criteria. Based on the results of the EV-301 study (NCT03474107), the European Society for Medical Oncology's Magnitude of Clinical Benefit Scale assigned a score of 4 out of 5 to enfortumab vedotin administered after chemotherapy and immunotherapy. The National Comprehensive Cancer Network's Evidence Blocks enabled assessment of enfortumab vedotin compared with other treatments for locally advanced or metastatic urothelial carcinoma, resulting in the positioning of enfortumab vedotin as a preferred regimen after chemotherapy and immunotherapy. CONCLUSIONS: Application of value frameworks in oncology can contribute to informed value-based decision-making. However, comparisons across frameworks should be made with caution and limited to the same lines of treatment. Enfortumab vedotin may contribute to optimizing outcomes in patients previously treated with chemotherapy and immunotherapy for locally advanced or metastatic urothelial carcinoma.

Immunophenotypic and molecular changes during progression of papillary urothelial carcinoma.

PURPOSE: Urothelial carcinoma has various molecular subtypes, each with different tumor characteristics. Although it is known that molecular changes occur during tumor progression, little is known about the specifics of these changes. In this study, we performed transcriptional analysis to understand the molecular changes during tumor progression. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tumor tissues were obtained from 12 patients with muscle-invasive bladder cancer (MIBC). The invasive and non-invasive papillary areas were identified in papillary urothelial carcinoma specimens. Immunohistochemistry (IHC) and mRNA sequencing were performed for each tumor area. RESULTS: Patients with CK5/6-negative and CK20-positive non-invasive papillary areas were selected and classified into the IHC switch subgroup (CK5/6-positive and CK20-negative in the invasive area) and the IHC unchanged subgroup (CK5/6-negative and CK20-positive in the invasive area) according to the IHC results of the invasive area. We identified differences in the mRNA expression between the non-invasive papillary and invasive areas of the papillary MIBC tissue samples. In both the non-invasive papillary and invasive areas, the IHC switch subgroup showed basal subtype gene expression, while the IHC unchanged subgroup demonstrated luminal subtype gene expression. CONCLUSIONS: The non-invasive papillary area showed a gene expression pattern similar to that of the invasive area. Therefore, even if the non-invasive papillary area exhibits a luminal phenotype on IHC, it can have a basal subtype gene expression depending on the invasive area.

Immunotherapy Plus Chemotherapy Versus Chemotherapy Alone as First-Line Treatment for Advanced Urothelial Cancer: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Platinum-based chemotherapy (CTX) has historically been the primary treatment for advanced urothelial cancer (aUC), with limited alternative options. The therapeutic landscape experienced a paradigm shift following the results of the EV-302 and Checkmate-901 trials, which led to the approval of Enfortumab vedotin plus pembrolizumab (EV-P) as the preferred first-line treatment, and nivolumab plus CTX for those unable to receive the preferred regimen. Currently, further investigations are underway to explore PD-1 and PD-L1 inhibitors in the initial treatment of aUC. PATIENTS AND METHODS: We conducted a systematic search across PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) comparing immune checkpoint inhibitors (ICI)-CTX combinations versus CTX alone as first-line treatment for advanced UC. Employing a random-effects model, we pooled hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Our analysis encompassed 3 RCTs, involving 2162 participants, with 51.16% randomized to combination therapy with platinum-based CTX. Compared to CTX alone, immune-chemotherapy significantly improved overall survival (HR 0.84; 95% CI 0.75-0.93; P < .01), progression-free survival (HR 0.78; 95% CI 0.70-0.86; P < .01), and objective response rate (RR 1.20; 95% CI 1.06-1.36; P < .01), while elevating the risk of immune-related adverse events (P-value = .02). CONCLUSION: In this meta-analysis of RCTs, ICI plus CTX demonstrated a significant association with improved survival at the expense of an increased risk of immune-related adverse events. Therefore, our findings suggest that this combination should be considered as an initial treatment for aUC in platinum-eligible patients who cannot receive EV-P.

Rates of Systemic Therapy for Metastatic Bladder Cancer Are Lower in Unmarried Males and Females.

OBJECTIVE: Systemic therapy is guideline-recommended for metastatic urothelial carcinoma of the urinary bladder (UCUB). Unmarried status represents an important barrier to treatment access in many primaries. The importance of married status is unknown in the context of systemic therapy in metastatic UCUB and was addressed in the current study. METHODS: We relied on the Surveillance, Epidemiology, and End Results database (2004-2020) to identify patients with metastatic UCUB. Univariable and multivariable logistic regression models were fitted to address systemic therapy rates. Additionally, temporal trends were plotted. RESULTS: Overall, 6873 patients with stage IV UCUB were identified. Of those, 4853 (71%) were male. Of males, 2993 (62%) were married vs. 797 (39%) of females. The rates of systemic therapy were 55% in both married males and married females. Married males and females differed from their unmarried counterparts regarding age and race/ethnicity. In males, prior to any adjustment, married status was associated with an odds ratio of 1.46 (P < .001). After adjustment for age and race/ethnicity, the odds ratio increased to 1.73 (P < .001). In females, prior to any adjustment, married status was associated with an odds ratio of 1.94 (P < .001). After adjustment for age and race/ethnicity, the odds ratio decreased to 1.57 (P < .001). CONCLUSION: Unmarried males and unmarried females are significantly exposed to lower access to systemic therapy compared to their married counterparts. In consequence, both unmarried men and unmarried women should be given very careful consideration when use of systemic therapy in metastatic UCUB is contemplated.

Metastatic Tropism in Urothelial Carcinoma With Variant Histology: A Comprehensive NCDB Analysis.

INTRODUCTION: Bladder cancer (BCa) with variant histology (VH) is notably aggressive and not as well studied as pure urothelial carcinoma (UC). The characteristics of variant BCa in the setting of metastatic disease may contribute to treatment response/resistance and subsequent disease progression. In this study, we sought to assess VH's impact on metastasis sites at presentation in metastatic BCa. METHODS: The National Cancer Database was queried from 2004 to 2019 to analyze cT1-4 cN0-3 cM1 patients with UC and VH BCa. The primary endpoint was the presence of metastasis to different organs. Binomial multivariable logistic regression was performed to determine the impact of VH on metastatic sites while controlling for multiple variables. RESULTS: Total 6005 eligible patients diagnosed with either UC or VH were included. Patients with small cell histology, the second most common VH, were more likely to have liver metastasis (OR: 4.335) while less likely to have lung metastases (OR: 0.521). Squamous cell carcinoma decreased the odds of bone metastasis (OR: 0.449). Adenocarcinoma increased the odds of lung metastases (OR: 1.690). Micropapillary VH is less likely to metastasize to the lungs (OR: 0.182) but more likely to spread to nonregional lymph nodes (OR: 2.623). Sarcomatoid subtype did not exhibit a statistically significant variation in the odds ratio for any of the metastatic sites. CONCLUSION: This study comprehensively analyzes the limited research regarding metastatic BCa and VH. Our analysis underscores each subtype exhibiting heterogeneous metastatic tropism. Importantly, these findings illustrate the role of routine somatic gene expression profiling to guide adequate staging and treatment intensification and to offer a foundation for future studies of VH BCa care.

An evaluation of mitomycin-containing reverse thermal gel for the treatment of low-grade upper tract urothelial carcinoma.

INTRODUCTION: Endoscopic management of upper tract urothelial carcinoma (UTUC) is increasingly relevant with greater detection of low-grade disease and guidelines recommending kidney preservation for low-risk disease. Historically, laser or thermal ablation has served as the primary tool for endoscopic management of UTUC, however, chemoablation is rapidly being developed to serve as a primary or adjuvant treatment option, which warrants review. AREAS COVERED: The current literature was reviewed to compare the outcomes and clinical utility of endoscopic treatment modalities for low-grade UTUC, with a focus on mitomycin-containing reverse thermal gel (UGN-101). EXPERT OPINION: The overall outcomes of mitomycin-containing gel therapy are promising, but adverse effects such as ureteral stricture call for careful consideration when using this treatment. We believe it is reasonable to consider use of mitomycin-containing gel as an adjuvant chemotherapy with endoscopic laser resection of low-grade upper tract urothelial carcinoma.

The Impact of Fibroblast Growth Factor Receptor Alterations in Clinical Outcomes of Patients With Advanced Urothelial Carcinoma: Real-World Data From a Latin American Population.

INTRODUCTION: Fibroblast growth factor receptor (FGFR) mutations and fusions are relevant biomarkers in metastatic urothelial carcinoma (mUC). However, the prevalence of genomic alterations and their impact on clinical outcomes in a Latin American population remains unknown. This study aimed to explore the prevalence of FGFR mutations and/or fusions in patients with mUC in Latin America (LATAM) and its association with clinicopathological characteristics, Bellmunt's prognostic model, and survival outcomes. PATIENTS AND METHODS: A multicenter retrospective cohort study from 2016 to 2019 of patients with mUC from several LACOG LATAM institutions. FGFR alterations were analyzed by real-time PCR and/or next-generation sequencing in tumor samples and clinicopathologic characteristics and survival outcomes data were collected. The prevalence of FGFR, patient characteristics, and treatment in real-world settings were summarized. Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate the associations of FGFR mutation and/or fusion status with median overall survival (mOS), median time to treatment failure (mTTF), and clinicopathological characteristics. RESULTS: In total, 222 patients were screened. Of these, 196 patients were considered eligible and were included in the analysis. FGFR mutations and/or fusions were found in 35 (17.9%) patients. There was no statistical difference in mOS and mTTF in FGFR-altered and non-altered patients (13.1 vs. 16.8 months, P = .20 and 3.9 vs. 4.1 months, P = .96, respectively). Bellmunt's prognostic model correctly predicted overall survival (P = .049). CONCLUSIONS: This is the largest study evaluating the prevalence of FGFR alterations in patients with mUC in the LATAM population. FGFR alterations in mUC were found in 17.9% of the patients, and the presence of this biomarker was not associated with OS. We validated Bellmunt's prognostic model in this cohort.

CT and MRI features of sarcomatoid urothelial carcinoma of the bladder and its differential diagnosis with conventional urothelial carcinoma.

BACKGROUND: Sarcomatoid urothelial carcinoma (SUC) is a rare and highly malignant form of bladder cancer with a poor prognosis. Currently, there is limited information on the imaging features of bladder SUC and reliable indicators for distinguishing it from conventional urothelial carcinoma (CUC). The objective of our study was to identify the unique imaging characteristics of bladder SUC and determine factors that aid in its differential diagnosis. MATERIALS AND METHODS: This retrospective study enrolled 22 participants with bladder SUC and 61 participants with CUC. The clinical, pathologic, and CT/MRI data from both groups were recorded, and a comparison was conducted using univariate analysis and multinomial logistic regression for distinguishing SUC from CUC. RESULTS: The majority of SUCs were located in the trigone of the bladder and exhibited large tumor size, irregular shape, low ADC values, Vesical Imaging-Reporting and Data System (VI-RADS) score ≥ 4, the presence of necrosis, and an invasive nature. Univariate analysis revealed significant differences in terms of tumor location, shape, the maximum long-axis diameter (LAD), the short-axis diameter (SAD), ADC-value, VI-RADS scores, necrosis, extravesical extension (EVE), pelvic peritoneal spread (PPS), and hydronephrosis/ureteral effusion (p < .001 ~ p = .037) between SUCs and CUCs. Multinomial logistic regression found that only SAD (p = .014) and necrosis (p = .003) emerged as independent predictors for differentiating between SUC and CUC. The model based on these two factors achieved an area under curve (AUC) of 0.849 in ROC curve analysis. CONCLUSION: Bladder SUC demonstrates several distinct imaging features, including a high incidence of trigone involvement, large tumor size, and obvious invasiveness accompanied by necrosis. A bladder tumor with a large SAD and evidence of necrosis is more likely to be SUC rather than CUC.

Differential effect of surgical technique on intravesical recurrence after radical nephroureterectomy in patients with upper tract urothelial cancer: a systematic review and Meta-analysis.

CONTEXT: Radical nephroureterectomy (RNU) with bladder cuff resection is the standard treatment in patients with high-risk upper tract urothelial cancer (UTUC). However, it is unclear which specific surgical technique may lead to improve oncological outcomes in term of intravesical recurrence (IVR) in patients with UTUC. OBJECTIVE: To evaluate the efficacy of surgical techniques and approaches of RNU in reducing IVR in UTUC patients. EVIDENCE ACQUISITION: Three databases were queried in January 2024 for studies analyzing UTUC patients who underwent RNU. The primary outcome of interest was the rate of IVR among various types of surgical techniques and approaches of RNU. EVIDENCE SYNTHESIS: Thirty-one studies, comprising 1 randomized controlled trial and 1 prospective study, were included for a systematic review and meta-analysis. The rate of IVR was significantly lower in RNU patients who had an early ligation (EL) of the ureter compared to those who did not (HR: 0.64, 95% CI: 0.44-0.94, p = 0.02). Laparoscopic RNU significantly increased the IVR compared to open RNU (HR: 1.28, 95% CI: 1.06-1.54, p < 0.001). Intravesical bladder cuff removal significantly reduced the IVR compared to both extravesical and transurethral bladder cuff removal (HR: 0.65, 95% CI: 0.51-0.83, p = 0.02 and HR: 1.64, 95% CI: 1.15-2.34, p = 0.006, respectively). CONCLUSIONS: EL of the affected upper tract system, ureteral management, open RNU, and intravesical bladder cuff removal seem to yield the lowest IVR rate in patients with UTUC. Well-designed prospective studies are needed to conclusively elucidate the optimal surgical technique in the setting of single post-operative intravesical chemotherapy.

Do we need a re-TUR after en bloc resection of T1 stage bladder cancer?

BACKGROUND: A second look trans-urethral resection of the bladder (re-TUR) is recommended after the diagnosis of T1 high grade (T1HG) bladder cancer. Few studies have evaluated the results of re-TUR after a first en bloc resection (EBR) and none of them have specifically reported the pathological results on the field of previous T1 disease. OBJECTIVE: To report the rate of upstaging and the rate of residual disease (RD) on the field of T1HG lesions resected with EBR. MATERIALS AND METHODS: Between 01/2014 and 06/2022, patients from 2 centers who had a re-TUR after an EBR for T1HG urothelial carcinoma were retrospectively included. Primary endpoint was the rate of RD including the rate of upstaging to T2 disease on the scar of the primary resection. Secondary endpoints were the rate of any residual disease outside the field. RESULTS: Seventy-five patients were included. No muscle invasive bladder cancer lesions were found after re-TUR. Among the 16 patients who had a RD, 4 were on the resection scar. All of these lesions were papillary and high grade. RD outside the field of the first EBR was observed in 12 patients. CONCLUSION: After EBR of T1HG disease, none of our patients had an upstaging to MIBC. However, the rate of RD either on and outside the field of the EBR remains quite significant. We suggested that predictive factors of residual papillary disease (number of tumors at the initial TUR and concomitant CIS) might be suitable to select patient who will benefit of the re-TUR.

Primary exophytic urothelial carcinoma of the bladder: A case report.

RATIONALE: Bladder urothelial carcinoma (UC) is a common urinary system tumor that is generally diagnosed by cystoscopy combined with pathological biopsy. However, complete exophytic UC of the bladder is very rare and difficult to diagnose. Early diagnosis and accurate identification of such tumors, followed by aggressive surgical treatment, is essential for the management of these patients. PATIENT CONCERNS: An 84-year-old man was admitted to the hospital with dysuria, a poor diet, and significant weight loss. DIAGNOSIS: Pelvic computed tomography and magnetic resonance imaging revealed an exteriophytic round mass on the right lateral wall of the bladder. Cystoscopy revealed a necrotic mass on the right lateral wall of the bladder cavity, and no tumor cells were found following the biopsy. The tumor was removed via partial cystectomy, and the pathological result indicated high-grade muscle-invasive UC. INTERVENTIONS: The patient refused radical cystectomy and underwent laparoscopic partial cystectomy plus pelvic lymph node dissection followed by cisplatin plus gemcitabine chemotherapy. OUTCOMES: The patient's mental state and appetite were significantly improved after the urinary tube was removed 1 week after surgery. His general state was significantly improved after 1 month of follow-up but died of acute cerebral infarction 3 months after surgery. LESSONS: UC of the bladder may grow completely out of the bladder without symptoms such as gross hematuria; thus, early diagnosis is difficult. For high-risk individuals, regular imaging tests may help to detect tumors early. Partial cystectomy is a reliable surgical modality for bladder preservation in such patients.

Radiotherapy plus pembrolizumab for advanced urothelial carcinoma: results from the ARON-2 real-world study.

The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p < 0.001). The 1y-OS rate in the SBRT subgroup were significantly higher for both lower (63%) and upper tract UC (68%), for pure urothelial histology (63%) and variant histologies (58%), and for patients with bone (40%) and lymph-node metastases (61%). Median PFS was 4.8 months, 9.6 months and 5.8 months in the CRT, SBRT and no RT subgroups, respectively (p = 0.060). The 1y-PFS rate was significantly higher (48%) in the SBRT population and was confirmed in all patient subsets. The difference in terms of ORR was in favour of SBRT. Our real-world analysis showed that the use of SBRT/pembrolizumab combination may play a role in a subset of aUC patients to increase disease control and possibly overall survival.

The impact of bladder cuff excision on outcomes after nephroureterectomy for upper tract urothelial carcinoma: An analysis of the ROBUUST 2.0 registry.

OBJECTIVES: We sought to determine whether bladder cuff excision and its technique influence outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS AND MATERIALS: A multicenter, international, retrospective analysis using the ROBotic surgery for Upper tract Urothelial cancer Study (ROBUUST) 2.0 registry identified 1,718 patients undergoing RNU for UTUC between 2015 and 2023 at 17 centers across the United States, Europe, and Asia. Data was gathered on (1) whether bladder cuff excision was performed and (2) what technique was used, including formal excision or other techniques (pluck technique, stripping/intussusception technique) and outcomes. Multivariate and survival analyses were performed to compare the groups. RESULTS: Most patients (90%, 1,540/1,718) underwent formal bladder cuff excision in accordance with EAU and AUA guidelines. Only 4% (68/1,718) underwent resection using other techniques, and 6% (110/1,718) did not have a bladder cuff excised. Median follow up for the cohort was 24 months (IQR 9-44). When comparing formal bladder cuff excision to other excision techniques, there were no differences in oncologic or survival outcomes including bladder recurrence-free survival (BRFS), recurrence-free survival (RFS), metastasis-free survival (MFS), overall survival (OS), or cancer-specific survival (CSS). However, excision of any kind conferred a decreased risk of bladder-specific recurrence compared to no excision. There was no difference in RFS, MFS, OS, or CSS when comparing bladder cuff excision, other techniques, and no excision. CONCLUSIONS: Bladder cuff excision improves recurrence-free survival, particularly when considering bladder recurrence. This benefit is conferred regardless of technique, as long as the intramural ureter and ureteral orifice are excised. However, the benefit of bladder cuff excision on metastasis-free, overall, and cancer-specific survival is unclear.

[Several key and difficult issues related to the grading of urothelial carcinoma of urinary bladder].

Grading and staging are the most important prognostic factors for both non-invasive and invasive urothelial carcinomas, and are also one of the most common difficulties encountered by pathologists in the daily diagnostic practice of urothelial carcinoma. Recently, the International Society of Urological Pathology organized a survey and questionnaire conference on various issues related to the diagnosis, grading, and staging of urothelial carcinoma, and ultimately formed a series of consensus opinions. This article briefly summarizes the consensus opinions of this series, and combines them with the current pathological diagnosis status of urothelial carcinoma in China. It briefly comments on how to apply this series of consensus opinions in the daily diagnostic practice of pathologists, deeply understand relevant diagnostic problems, and carry out relevant clinical pathological research to further solve problems.

No difference in oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving radical nephroureterectomy.

Patients with end stage renal disease (ESRD) are at high risk of developing upper tract urothelial carcinoma (UTUC). Due to high recurrence rate of UTUC in contralateral kidney and ureter, and high risk of complications related to surgery and anesthesia, whether it's necessary to remove both kineys and ureters at one time remains in debate. We utilized Taiwanese UTUC Registry Database to valuate the difference of oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving surgical resection. Patients with ESRD and UTUC were divided into three groups, unilateral UTUC, previous history of unilateral UTUC with metachronous contralateral UTUC, and concurrent bilatetral UTUC. Oncological outcomes, perioperative complications, and length of hospital stays were investiaged. We found that there is no diffence of oncological outcomes including overall survival, cancer specific survival, disease free survival and bladder recurrence free survival between these three groups. Complication rate and length of hospital stay are similar. Adverse oncological features such as advanced tumor stage, lymph node involvement, lymphovascular invasion, and positive surgical margin would negatively affect oncological outcomes.

Urinary Tract Cytopathology: Current and Future Impact on Patient Care.

Urine cytology is a non-invasive, cost-efficient, and sensitive test to detect high-grade urothelial carcinoma. The Paris System (TPS) for Reporting Urinary Cytology is an evidence-based system that uses the risk of malignancy to guide patient management. Since its inception, TPS has standardized urine cytology reports, facilitating communication among pathologists and between pathologists and clinicians. It is imperative to correlate the urine cytology findings with the concurrent tissue sample to avoid false-negative and false-positive results when possible. Several ancillary tests and artificial intelligence algorithms are being developed to increase the accuracy of urine cytology interpretation.