Metachronous urothelial carcinoma in the renal pelvis,bladder,and urethra:A case report

BACKGROUND Urothelial carcinoma(UC)is a common malignancy of the urinary system that can occur anywhere from the renal pelvis to the proximal urethra.Most UCs are in the bladder and have multifocal growth.Upper urinary tract UC(UTUC),which occurs in the renal pelvis or ureter,accounts for only 5%to 10%of UCs.CASE SUMMARY In March 2015,a 70-year-old male who initially presented to a local hospital with a complaint of painless hematuria was diagnosed with UTUC of the right renal pelvis.The doctors administered radical nephroureterectomy and bladder cuff excision.Although the doctors recommended intravesical chemotherapy and regular follow-up,he rejected this advice.In December 2016,the patient presented at our hospital with dysuria.We identified UC in the residual bladder and administered radical cystectomy and left cutaneous ureterostomy.In November 2021,he presented again with urethral bleeding.We detected urethral UC as the cause of urethral orifice bleeding and administered radical urethrectomy.Since then,he has visited regularly for 6-mo follow-ups,and was in stable condition as of December 2022.CONCLUSION UTUC is prone to seeding and recurrence.Adjuvant instillation therapy and intense surveillance are crucial for these patients.

Hyperprogression after anti-programmed death-1 therapy in a patient with urothelial bladder carcinoma:A case report

BACKGROUND Immune checkpoint inhibitors,including programmed death-ligand 1(PD-L1)and programmed death-1(PD-1)have recently been approved to treat locally advanced and metastatic urothelial carcinoma(UC).However,some patients experience rapid tumor progression rather than any clinical benefit from anti-PDL1/PD-1 therapy.CASE SUMMARY A 73-year-old woman with bladder UC showed the progression of multiple metastases after surgery and chemotherapy for over 12 mo.The patient could not tolerate further chemotherapy.Next-generation sequencing was performed,and the results indicated that the tumor mutational burden was 6.4 mutations/Mb.The patient received the anti-PD-L1 agent toripalimab combined with albuminbound paclitaxel.Compared with the baseline staging before immunotherapy,the patient had a treatment failure time of<2 mo,an increase in tumor burden of>50%,and a>2-fold increase in progression,indicating hyperprogression.CONCLUSION Selecting patients most likely to respond to treatment with immunotherapeutic agents remains challenging.For older patients with advanced UC who have already exhausted multi-line chemotherapy options,immunotherapy should be used prudently if no effective biomarker is available.Further studies are required to clarify the causes and mechanisms of hyperprogression.

WNT/β-catenin signaling in urothelial carcinoma of bladder

Urothelial carcinoma of bladder is the second most prevalent genitourinary disease.It is a highly heterogeneous disease as it represents a spectrum of neoplasms,including non-muscle invasive bladder cancer(NMIBC),muscle invasive bladder cancer(MIBC)and metastatic lesions.Genome-wide approaches and candidate gene analysis suggest that malignant transformation of the bladder is multifactorial and a multitude of genes are involved in the development of MIBC or NMIBC phenotypes.Wnt signaling is being examined to control and maintain balance between stemness and differentiation in adult stem cell niches.Owing to its participation in urothelial development and maintenance of adult urothelial tissue homeostasis,the components of Wnt signaling are reported as an important diagnostic and prognostic markers as well as novel therapeutic targets.Mutations/epigenetic alterations in the key molecules of Wnt/β-catenin canonical pathway have been linked with tumorigenesis,development of drug resistance and enhanced survival.Present review extends our understanding on the functions of key regulatory molecules of canonical Wnt/β-catenin pathway in urothelial tumorigenesis by inducing cancer stem cell phenotype(UCSCs).UCSCs may be responsible for tumor heterogeneity,high recurrence rates and complex biological behavior of bladder cancer.Therefore,understanding the role of UCSCs and the regulatory mechanisms that are responsible for high relapse rates and metastasis could help to develop pathway inhibitors and augment current therapies.Potential implications in the treatment of urothelial carcinoma of bladder by targeting this pathway primarily in UCSCs as well as in bulk tumor population that are responsible for high relapse rates and metastasis may facilitate potential therapeutic avenues and better prognosis.

The role of aberrant promoter hypermethylation of DACT1 in bladder urothelial carcinoma

The purpose of this study was to determine the relationship between hypermethylation of DACT1 gene pro-moter and lower mRNA expression in bladder urothelial carcinoma tissue.The methylation status of 29 urothelial carcinoma samples and 29 normal tissue samples were examined by methylation-specific polymerase chain reac-tion（MSP）.The DACT1 mRNA transcript levels and DACT1 protein levels in all samples were then evaluated to define the relationship between the methylation status of the DACT1 promoter and its expression at the transcrip-tional and translational levels.Decreased expression of DACT1 was detected in 89.66% of urothelial carcinomas（26/29;P 〈 0.005）.Promoter hypermethylation was found in 58.62%（17/29） urothelial carcinomas and 25%（7/29） normal tissues,respectively（P 〈 0.05）.DACT1 expression was lower in tissues where the DACT1 gene promoter was hypermethylated than in unmethylated tissues（0.25±0.17 vs 0.69±0.30,P 〈 0.05）.DACT1 gene hyper-methylation was closely related to tumor size,grade and stage（P 〈 0.05）.Our results indicate that silencing and downregulation of DACT1 mRNA may be implicated in carcinogenesis and the progression of bladder urothelial carcinoma,and may be a potential prognostic factor.

Infiltration Related miRNAs in Bladder Urothelial Carcinoma

This study aimed to investigate infiltration related microRNAs(miRNAs) in bladder urothelial carcinoma(BUC).Twenty patients with BUC were enrolled and divided into 2 groups according to infiltration or not:infiltrating BUC group(n=12) and non-infiltrating BUC group(n=8).Gene chip was used to detect infiltration related miRNAs in the BUC samples.In other recruited 17 patients with BUC who were divided into infiltrating BUC samples(n=14) and non-infiltrating BUC samples(n=3),and in 4 BUC cell lines(EJ,5637,T24 and BIU-87),the expression of miRNAs was assayed by using reverse transcription-polymerase chain reaction(RT-PCR).In infiltrating BUC group,as compared with non-infiltrating BUC group,there were 7 differentially expressed miRNAs:hsa-miR-29c,hsa-miR-200a,hsa-miR-378,hsa-miR-429,hsa-miR-200c and hsa-miR-141 were up-regulated,while hsa-miR-451 was down-regulated.In the BUC samples,the results of RT-PCR were consistent with those by the miRNA array.In the cancer cell lines,RT-PCR in T24 only revealed the similar expression pattern of miRNAs to that by the miRNA array.It is suggested that infiltration of BUC is related with different expression of miRNAs,which may provide a novel platform for further study on function and action mechanism of miRNAs.

Complete response to trastuzumab and chemotherapy in recurrent urothelial bladder carcinoma with HER2 gene amplification: A case report

BACKGROUND Targeted treatments may greatly affect the natural history of urothelial carcinoma based on their pharmacokinetics. A phase II trial has explored the combination of cytotoxic chemotherapy with the anti-HER-2 monoclonal antibody trastuzumab in selected patients with metastatic bladder cancer, but it failed.CASE SUMMARY Here, we report a case of recurrent urothelial bladder carcinoma(UBC) in a patient who has undergone three operations, and further illuminate its diagnosis and treatment. The diagnosis of UBC was rendered according to the pathological indices. Next-generation sequencing on formalin fixed paraffin-embedded(FFPE)tissue was also performed and suggested HER2 gene amplification in the FFPE tissue. Based on HER2 gene amplification in FFPE, the patient was treated with chemotherapy in combination with trastuzumab after his third surgery.Fortunately, the patient got a clinically complete remission to trastuzumab for 34 mo.CONCLUSION There is not enough clinical evidence for incorporating trastuzumab in routine treatment of UBC. This case hinted that recurrent UBC patients with HER2 gene amplification may benefit from targeted trastuzumab. Further studies are needed to further investigate the status of HER2 gene and better determine trastuzumab in the management of UBC.

A Combined Clinicopathologic Analysis of 658 Urothelial Carcinoma Cases of Urinary Bladder

Objective To study the clinicopathological features of patients with urothelial carcinoma of the urinary bladder (UCB), and analyze the association of clinicopathological characteristics with tumor recurrence and progression. Methods Altogether 658 UCB cases in Fudan University Shanghai Cancer Center were collected from January 2006 to December 2010. The histopathologic materials and the clinical records were reviewed. Univariate and multivariate analyses were preformed to detect the association. Results The mean age of the patients was 61.97±12.97 years (range, 20-90 years). Male to female ratio was about 5:1. A total of 517 cases (78.6%) were superficial at the time of diagnosis (stage Ta/T1). The mean follow-up period was 22.36±24.92 months. Twenty-five patients lacking follow-up information were excluded in calculating recurrence and progression rates, the recurrence rate was about 37.0% (234/633), and progression rate about 6.2% (39/633). Three variables (grade, tumor growth pattern, and pathological stage) were found to be significant risk factors for tumor progression in univariate and multivariate analyses (P<0.05). Conclusions Most of the newly diagnosed UCB cases may be superficial diseases. Grade, tumor growth pattern, and pathological stage are associated with tumor progression of UCB.

Predictive Factors of Bladder Tumor Recurrence after Nephro-Ureterectomy for Urothelial Carcinoma

Objectives: To evaluate the incidence of bladder cancer after nephro-ureterectomy (NUT) and determine the potential risk factors of bladder recurrence in patients with upper urinary tract urothelial carcinoma (UUT-UC). Materials and Methods: We retrospectively assessed 37 patients with UUT-UC including a significant follow-up after NUT of 34 months (range 12 - 120 months). The median age of the population was 72 years (range 48 - 83 years). Patients with a previous history of bladder cancer, concomitant diagnosis of bladder tumor and UUT-UC;or a metastatic UUT-UC were excluded from the study. Results: Out of these 37 patients, 17 presented a bladder recurrence within an average time of 12 months (range 3 to 31 months) after the NUT. In 94% of the cases, bladder recurrence occurred within the first 24 months following the NUT. Histological distribution was: 13 Ta tumors (76%), 2 pT1 tumors (11.7%);11 patients had a high stage lesion (76%), whereas 4 patients had a low stage lesion (23.5%). As regards the anatomo-pathological characteristics of the UUT-UC, the supra iliac localization of the tumor is a significant risk factor of bladder recurrence (p = 0.04). Conclusion: Bladder recurrence after NUT occurred frequently and could have possibly been under-estimated. The use of intra-vesical instillation of Mitomycin C after NUT has been recently recommended by the European Association of Urology, but no predictive factors have yet been identified. Early diagnosis of bladder recurrence could certainly have reduced mortality in this patient population.

Mutational analysis of Ras hotspots in patients with urothelial carcinoma of the bladder

BACKGROUND Mutational activation of Ras genes is established as a prognostic factor for the genesis of a constitutively active RAS-mitogen activated protein kinase pathway that leads to cancer.Heterogeneity among the distribution of the most frequent mutations in Ras isoforms is reported in different patient populations with urothelial carcinoma of the bladder(UCB).AIM To determine the presence/absence of mutations in Ras isoforms in patients with UCB in order to predict disease outcome.METHODS This study was performed to determine the mutational spectrum at the hotspot regions of H-Ras,K-Ras and N-Ras genes by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)and DNA sequencing followed by their clinical impact(if any)by examining the relationship of mutational spectrum with clinical histopathological variables in 87 UCB patients.RESULTS None of the 87 UCB patients showed point mutations in codon 12 of H-Ras gene;codon 61 of N-Ras gene and codons 12,13 of K-Ras gene by PCR-RFLP.Direct DNA sequencing of tumor and normal control bladder mucosal specimens followed by Blastn alignment with the reference wild-type sequences failed to identify even one nucleotide difference in the coding exons 1 and 2 of H-Ras,NRas and K-Ras genes in the tumor and control bladder mucosal specimens.CONCLUSION Our findings on the lack of mutations in H-Ras,K-Ras and N-Ras genes could be explained on the basis of different etiological mechanisms involved in tumor development/progression,inherent genetic susceptibility,tissue specificity or alternative Ras dysfunction such as gene amplification and/or overexpression in a given cohort of patients.

A clinical analysis and prognostic study of 62 cases with T1G3 urothelial carcinoma of the bladder

Objective:The aim of our study was to clarify the clinicopathological factors affecting the outcome of T1G3 urothelial carcinoma of the bladder.Methods:We retrospectively reviewed 62 cases of T1G3 bladder cancer treated with transuretheral resection of bladder toumor (TURBT) followed by intravesical instillation between 1997 and 2009.Cumulative survival was analyzed by Kaplan-Meier method.Cox regression was used for univariate and multivariate analysis.Log-rank method was used for the significance test.The statistical difference was accepted when the P value was lower than 0.05.Results:Median follow-up period was 40 months (6-140 months).Forty-one cases of intravesical recurrence (66%) were observed during follow-up.Two-and 5-year recurrence-free survival rates were 43.4% and 35.1%.Fourteen cases of progression (23%) were observed during the follow-up period.Two-and 5-year progression-free survival rates were 86.4% and 83.5%,respectively.Significant factors for tumor recurrence and progression were analyzed by Cox regression.Tumor multiplicity (RR=2.250),size (RR=1.039) and history of recurrence (RR=2.162) were significantly correlated with recurrence and tumor multiplicity (RR=3.695) was significantly correlated with progression on multivariate analysis.Conclusion:Tumor multiplicity,size,history of recurrence were correlated with recurrence and tumor multiplicity was significantly correlated with progression.Tumor multiplicity,size and history of recurrence should be taken into account when we make therapy strategies for T1G3 urothelial carcinoma of the bladder.

Progress in the treatment of Bladder Urothelial Carcinoma with PD-1 / PD-L inhibitor

Bladder cancer is one of the most common cancers in the world, and about 80%-90% of bladder cancers are urothelial cancer. Neoadjuvant platinum-based combination chemotherapy is considered to be the standard treatment for bladder cancer. However, the use of this treatment has clinical disadvantages such as small overall benefit, toxic effects on the target population, and inability to select the most beneficial patients. This phenomenon has been improved by the presence of immunological checkpoint inhibitors, of which PD-1/PDL-1 inhibitors are one of them. The use of PD-1/ PD-L1 in urinary cancer is a new treatment and offers new hope for the treatment of platinum-refractory metastatic urothelial bladder cancer. Related drugs have now been approved for use in patients with refractory or unqualified platinum-based chemotherapy drugs. Clinical trials are currently underway to determine how best to use these drugs, and whether they should be used alone or in combination with other treatments. This article will review the research progress of PD-1/PDL-1 inhibitors in bladder tumors.

Analysis of low expression of ferroptosis-related gene DECR1 on poor prognosis and immune cell defects of bladder urothelial carcinoma

Background:Ferroptosis is an iron dependent form of cell death,which plays an important role in the pathogenesis of a variety of urinary malignancies.The down-regulation of DECR1 gene causes the accumulation of polyunsaturated fatty acids(PUFAs),increases the susceptibility to lipid peroxidation,and finally leads to cell death.Methods:We first searched the data to find reductase 1(DECR1)expression in bladder uroepithelial carcinoma and healthy surrounding tissues in the Cancer Genome Atlas(TCGA),and we then confirmed DECR1 expression with additional independent cohorts in the Gene Expression Omnibus(GEO)database and the Human Protein Atlas(HPA).In order to determine the link between DECR1 expression and clinical traits and overall survival(OS),as well as to create nomograms,multivariate analysis and Kaplan Meier survival curves were utilized.Through the use of an online string website,the network of proteins that interact with DECR1 was created.Through an online string website,the protein network interacting with DECR1 was built.Finally,we looked at the association between aggressive immune cells and the marker genes that belong to them and DECR1 expression.Results:When compared to normal tissues,bladder tumor tissues had higher DECR1 expression(P=0.002).Low DECR1 expression was linked with tumor grade and stage in tumor cells.BLCA patients with low DECR1 expression had a lower overall survival than BLCA patients with high DECR1 expression,according to a survival study(P=0.008).The protein network’s HSD17B4 and DECR1 connections are crucial.The expression of regulatory T cells,regulatory B cells,and their markers were decreased when DECR1 was missing in bladder cancer.Conclusion:Decreased DECR1 expression was associated with BLCA progression,poor prognosis and impaired infiltration of some immune cells.

Expression of Snail in bladder urothelial carcinoma and its relationship with E-cadherin and a subset of T cell groups

Objective To investigate the expression of Snail in bladder urothelial carcinoma and evaluate its relationship with E-cadherin and a subset of T cell groups. Methods Immunohistochemical method was used to detect the expression of Snail and E-cadherin proteins in tissue

Oncological impact of different distal ureter managements during radical nephroureterectomy for primary upper urinary tract urothelial carcinoma

BACKGROUND The current standard surgical treatment for non-metastatic upper urinary tract urothelial carcinoma(UTUC)is radical nephroureterectomy(RNU)with bladder cuff excision(BCE).Typically,BCE techniques are classified in one of the following three categories:An open technique described as intrasvesical incision of the bladder cuff,a transurethral incision of the bladder cuff(TUBC),and an extravesical incision of the bladder cuff(EVBC)method.Even though each of these management techniques are widely used,there is no consensus about which surgical intervention is superior,with the best oncologic outcomes.AIM To investigate the oncological outcomes of three BCE methods during RNU for primary UTUC patients.METHODS We retrospectively analyzed the data of 248 primary UTUC patients,who underwent RNU with BCE between January 2004 to December 2018.Patients were analyzed according to each BCE method.Data extracted included patient demographics,perioperative parameters,and oncological outcomes.Statistical analyses were performed using chi-square and log-rank tests.The Cox proportional hazards regression model was utilized to identify independent predictors.P<0.05 was considered statistically significant.RESULTS Of the 248 participants,39.9%(n=99)underwent intrasvesical incision of the bladder cuff,38.7%(n=96)EVBC,and 21.4%(n=53)TUBC.At a median followup of 44.2 mo,bladder recurrence developed in 17.2%,12.5%,and 13.2%of the cases,respectively.Cancer-specific deaths occurred in 11.1%,5.2%,and 7.5%of patients,respectively.Kaplan-Meier survival curves with a log-rank test highlighted no significant differences in intravesical recurrence-free survival,cancer-specific survival,and overall survival among these approaches with P values of 0.987,0.825,and 0.497,respectively.Multivariate analysis showed that the lower ureter location appears to have inferior intravesical recurrence-free survival(P=0.042).However,cancer-specific survival and overall survival were independently influenced by tumor stage(hazard ratio[HR]=8.439;95%con
dence interval:2.424-29.377;P=0.001)and lymph node status(HR=14.343;95%CI:5.176-39.745;P<0.001).CONCLUSION All three techniques had comparable outcomes;although,EVBC and TUBC are minimally invasive.While based upon rather limited data,these findings will support urologists in blending experience with evidence to inform patient choices.However,larger,rigorously designed,multicenter studies with long term outcomes are still required.

Clinical implications of single cell sequencing for bladder cancer

Bladder cancer(BC)is the 10th most common cancer worldwide,with about 0.5 million reported new cases and about 0.2 million deaths per year.In this scoping review,we summarize the current evidence regarding the clinical implications of single-cell sequencing for bladder cancer based on PRISMA guidelines.We searched PubMed,CENTRAL,Embase,and supplemented with manual searches through the Scopus,and Web of Science for published studies until February 2023.We included original studies that used at least one single-cell technology to study bladder cancer.Forty-one publications were included in the review.Twenty-nine studies showed that this technology can identify cell subtypes in the tumor microenvironment that may predict prognosis or response to immune checkpoint inhibition therapy.Two studies were able to diagnose BC by identifying neoplastic cells through single-cell sequencing urine samples.The remaining studies were mainly a preclinical exploration of tumor microenvironment at single cell level.Single-cell sequencing technology can discriminate heterogeneity in bladder tumor cells and determine the key molecular properties that can lead to the discovery of novel perspectives on cancer management.This nascent tool can advance the early diagnosis,prognosis judgment,and targeted therapy of bladder cancer.

Histologic subtypes of non-muscle invasive bladder cancer

The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characterization of histologic subtypes(HS)in UC in BC have mainly been described in muscle in-vasive bladder cancer(MIBC).However,the currently used classification is ap-plied for invasive urothelial neoplasm and therefore,also valid for a subset of NMIBC.The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known.HS in NMIBC are associated with an aggressive phenotype.Conse-quently,clinical guidelines categorize HS of NMIBC as“(very)high-risk”tumors and recommend offering radical cystectomy to these patients.Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials.Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively invest-igated in the context of HS in NMIBC.Further evaluation prior to implementation into clinical practice is needed.

Metastatic urothelial carcinoma harboring ERBB2/3 mutations dramatically respond to chemotherapy plus anti-PD-1 antibody:A case report

BACKGROUND Immune checkpoint inhibitors(ICIs)targeting the programmed death(PD)-1 pathway have substantially changed the clinical management of metastatic urothelial carcinoma(m UC);however,the response rate remains low.There are ongoing efforts to identify robust biomarkers that can effectively predict the treatment response to ICIs.Previous studies have suggested that ERBB2/3 mutations are associated with the efficacy of ICIs in gallbladder carcinoma.CASE SUMMARY We present a 59-year-old man with m UC harboring ERBB2/3 mutations(in-frame insertion of ERBB2 and ERBB3 amplification),negative PD-ligand 1 expression,and low tumor mutation burden.He received anti-PD-1 antibodies and paclitaxel as second-line treatment.After two cycles of treatment,the lung metastases had significantly shrunk,achieving good partial remission.After six cycles of combination therapy,the patient received sindilimab 200 mg once every 3 wk as maintenance monotherapy.At the last follow-up,the patient continued to exhibit a partial response and progression-free survival for as long as 19 mo.CONCLUSION ERBB2/3 mutations may represent a predictive biomarker for selecting a subgroup of m UC patients who will benefit from ICIs.

Practice change in the management of metastatic urothelial carcinoma after ASCO 2020

Metastatic urothelial carcinoma(mUC)is an incurable and aggressive disease.In the past decades there have been few effective treatment options that have impacted the prognosis of mUC patients.However,in the last few years,several drugs have emerged as new treatment choices that are changing the therapeutic landscape of mUC.Immune checkpoint inhibitors(ICIs)and targeted agents are useful treatment strategies that have been incorporated into our clinical practice.Nevertheless,cisplatin-based chemotherapy is still the standard of care in the first-line of metastatic disease.The results of the JAVELIN Bladder 100 phase 3 trial were presented at ASCO 2020,this trial evaluated the role of avelumab,an ICI,as maintenance therapy in patients who had not progressed after first-line platinum-based chemotherapy.The trial met its primary endpoint demonstrating an overall survival benefit with avelumab maintenance.In addition,new drugs and combinations are being evaluated to improve the outcomes of second and subsequent lines.Fibroblast growth factor receptor(FGFR)inhibitors and immunotherapy combinations were some of the strategies presented at ASCO 2020 that have shown promising results.Finally,the development of predictive biomarkers that help us in the decision-making process will be one of the most important challenges in the next years.

The emerging role of somatic tumor sequencing in the treatment of urothelial cancer

The development of rapid genome sequencing has greatly enhanced our understanding of the molecular biology underlying many malignancies.Whole exome sequencing has highlighted the individualistic nature of malignancies on a patient-to-patient basis and begun to revolutionize therapeutic approaches.In recent years,whole genome sequencing of urothelial malignancies has identified a host of somatic mutations which contribute to growth,progression,and metastasis of urothelial carcinoma of the bladder and upper tract urothelial carcinoma.As genetic sequencing continues,additional targets will be identified,allowing development of novel therapeutic agents targeting cancer on a molecular level,with the goal of delivering highly individualized care based on the underlying mutational profile of the patient’s malignancy.In this review,we aim to discuss known genetic alterations of urothelial malignancy and the implications these mutations carry in terms of prognostication and development of targeted therapeutic agents.We will focus on RNA-expression profiling and genomic DNA profiling,with a focus on comprehensive whole exome and whole genome sequencing relative to selected urothelial carcinoma-associated genes and circulating tumor DNA analysis.

A Case Report of an Inverted Papilloma of the Prostatic Urethra and a Synchronous Low-Grade Papillary Carcinoma of the Bladder

Inverted urothelial papilloma is a rare benign tumour and represents one of the urothelial lesions with inverted morphology. Accurate diagnosis and differentiation from other inverted lesions is important because its proper clinical management and expected clinical outcomes are distinctly different. Here we describe a case of a large inverted urothelial papilloma of the prostatic urethra and a synchronous non-invasive low-grade papillary urothelial carcinoma of the bladder in a 60 year-old man. We focus on the differential diagnosis of inverted urothelial papilloma.