Concurrent occurrence of adenocarcinoma and urothelial carcinoma of the prostate gland:A case report

BACKGROUND Adenocarcinoma is the most common subtype of prostate cancer.Prostatic urothelial carcinoma(UC)typically originates from the prostatic urethra.The concurrent occurrence of adenocarcinoma and UC of the prostate gland is uncommon.CASE SUMMARY We present the case of an 82-year-old male patient with simultaneous adenocarcinoma and UC of the prostate gland.The patient underwent a transrectal ultrasound-guided biopsy,and the pathology test revealed UC.Subsequently,transurethral laser prostatectomy was performed,and the pathology test indicated adenocarcinoma of the prostate with a Gleason score of 3+4 and highgrade UC.Therefore,the patient was treated with androgen deprivation therapy,systemic chemotherapy,and immunotherapy.Magnetic resonance imaging performed during follow-up revealed a prostate tumor classified as cT2cN1M0,stage IVA.Therefore,the patient underwent robotic-assisted radical prostatectomy and bilateral pelvic lymph node dissection.The final pathology test of the prostate gland revealed acinar-type adenocarcinoma,Gleason pattern 4+3,pT2N0M0,and high-grade UC.The patient regularly presented to the clinic for postoperative follow-up evaluations.He did not experience any urinary discomfort.CONCLUSION According to our literature review,this is the first reported case of coexisting adenocarcinoma and UC of the prostate gland.

Conservative management of an early abdominal complication during a Tullio percutaneous endoscopic excision of renal pelvis urothelial carcinoma:A case report

BACKGROUND Upper tract urothelial carcinoma(UTUC)representing only a small fraction of all urothelial tumors.It predominantly affects the renal pelvis in men,often coexisting with bladder carcinoma.UTUC displays a more aggressive genetic profile compared to bladder neoplasms,with the majority of patients presenting with advanced disease.Histologically,about a quarter of UTUC cases exhibit high-grade subtypes,associated with a worse prognosis.Tobacco use and past exposure to aromatic amines are significant risk factors for UTUC.Imaging modalities such as Uro-computed tomography and magnetic resonance imaging play crucial roles in diagnosis.Ureterorenoscopy is vital for direct visualization and biopsy sampling,but its limited sampling capacity presents challenges in determining tumor depth and staging.Traditionally,nephroureterectomy with bladder cuff excision has been the gold-standard treatment for UTUC.Endoscopic conservative treatment has recently emerged as a viable option for selected patients,offering comparable oncological outcomes to radical surgery.Percutaneous access is also feasible for larger intrarenal tumors.CASE SUMMARY We present a case of an 84-year-old woman who underwent percutaneous endoscopic excision of a renal pelvis neoplasm using the Tullio laser.Despite successful tumor removal,the patient experienced a postoperative complication with abdominal fluid leakage.Conservative management effectively resolved the complication.Given the patient's age and refusal for radical surgery,the conservative approach proved to be a valid therapeutic choice.CONCLUSION Overall,UTUC remains a diagnostic and therapeutic challenge due to its rarity.However,advances in endoscopic and percutaneous techniques provide valuable alternatives for selected patients,warranting further exploration in this evolving field.

Management Practices of Locally Advanced and Metastatic Urothelial Carcinoma: A Questionnaire-Based Survey among Lebanese Oncologists

Background and Objective: The outcome of locally advanced and metastatic urothelial carcinoma LA/mUC has improved over the past years with a plethora of new treatments and the approval of immune checkpoint inhibitors (ICIs), antibody-drug conjugates, and targeted agents, to identify locally advanced metastatic urothelial carcinoma’s current management practices in Lebanon and the implication of the ongoing economic crisis on the medical practice. Methods: An online questionnaire was used to survey ten Lebanese oncologists from six different hospitals, between July 5 and July 11, 2022, requesting information pertaining to their current clinical practice in the pharmacological treatment of locally advanced metastatic urothelial carcinoma. Key Findings: Cisplatin-based chemotherapy was the most frequently reported initial treatment of locally advanced metastatic urothelial carcinoma. Participants reported using immune checkpoint inhibitors in platinum-ineligible patients and those with PDL1 positive tumors. Also, they would not consider the concomitant use of immunotherapy and chemotherapy in the first-line setting. Participants believed that avelumab maintenance is effective in the absence of progression after first-line platinum-based chemotherapy;they would consider initiating it 2 - 10 weeks after completion of chemotherapy. Conclusions and Clinical Implications: After comparing with current international guidelines, this study shows that Lebanese oncologists follow international guidelines and have deep knowledge of recent clinical trials for the management of locally advanced metastatic urothelial carcinoma, regardless of economic crisis challenges.

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.

Coexistence of urinary tuberculosis and urothelial carcinoma:A case report

BACKGROUND Taiwan has a high prevalence of tuberculosis and urothelial carcinoma.However,the simultaneous occurrence of both disorders in one patient is uncommon.Tuberculosis and urothelial carcinoma share some common risk factors and could demonstrate overlapping clinical manifestations.CASE SUMMARY Herein,we report the case of a patient who presented with fever,persistent hematuria,and pyuria.Chest computed tomography scans revealed a bilateral upper lobes cavitary lesion with fibrosis.Severe hydronephrosis of the right kidney and renal stones and cysts in the left kidney were observed.Initial microbiological testing was negative;however,a polymerase chain reaction assay of the urine confirmed a urinary tuberculosis infection.The patient was started on an anti-tuberculosis regimen.Ureteroscopy performed to resolve obstructive nephropathy revealed the incidental finding of a left middle-third ureteral tumor.Examination after biopsy and transurethral resection of the bladder tumor indicated urothelial carcinoma.The patient underwent laparoscopic nephroureterectomy,with bladder cuff excision for the right kidney and ureter,and holmium laser ablation of the ureteral lesion to preserve the left kidney and ureter.He has remained stable after the procedures.CONCLUSION Although establishing a causal relationship between tuberculosis and cancer is difficult,medical personnel should consider their correlation.

Bladder preservation in complicated invasive urothelial carcinoma following treatment with cisplatin/gemcitabine plus tislelizumab:A case report

BACKGROUND Invasive urothelial carcinoma(UC)with squamous and glandular differentiation is a highly malignant and complicated pathological subtype,and the standard care is radical cystectomy(RC).However,urinary diversion after RC significantly reduces patient quality of life,thus bladder-sparing therapy has become a research hotspot in this field.Recently,five immune checkpoint inhibitors have been approved for systemic therapy of locally advanced or metastatic bladder cancer by the Food and Drug Administration,but the efficacy of immunotherapy combined with chemotherapy for invasive UC is still unknown,especially for pathological subtypes with squamous and glandular differentiation.CASE SUMMARY We report the case of a 60-year-old male who complained of repetitive painless gross hematuria and was diagnosed with muscle-invasive bladder cancer with squamous and glandular differentiation,defined as cT3N1M0 according to the American Joint Committee on Cancer,who had a strong desire to preserve the bladder.Immunohistochemical staining revealed that programmed cell deathligand 1(PD-L1)expression in the tumor was positive.Thus,a transurethral resection to maximize removal of the bladder tumor was performed under cystoscopy,and the patient subsequently received a combination of chemotherapy(cisplatin/gemcitabine)and immunotherapy(tislelizumab)treatment.No tumor recurrence in the bladder was observed following pathological and imaging examination after 2 cycles and 4 cycles of treatment,respectively.The patient achieved bladder preservation and has been tumor-free for more than two years.CONCLUSION This case shows that the combination of chemotherapy and immunotherapy might be an effective and safe treatment strategy for PD-L1 expression positive UC with divergent histologic differentiation.

Prognostic value of platelet-to-lymphocyte ratio in upper tract urothelial carcinoma patients treated with radical nephroureterectomy:A metaanalysis

Objective:To evaluate the prognostic value of platelet-to-lymphocyte ratio(PLR)in upper tract urothelial carcinoma(UTUC)patients treated with radical nephroureterectomy.Methods:This study was pre-registered in PROSPERO(No.CRD42020186645).Two reviewers independently performed a comprehensive literature search on PubMed,Web of Science,EMBASE,Cochrane Library databases,China Biology Medicine disc(CBM),Wanfang database,and China National Knowledge Infrastructure(CNKI)from inception to May 2021 for prospective or retrospective cohort studies evaluating the prognostic value of PLR.Literature was analyzed with inclusion and exclusion criteria.Data and other useful clinicopathological features were extracted and analyzed with fixed or random-effect models when applicable.Heterogeneity was assessed on the basis of Cochran’s Q test and I2 statistic.Publication bias was assessed with funnel plots and precisely assessed by Egger's tests.Results:A total of ten studies involving 3287 UTUC patients were included.Meta-analysis showed that elevated preoperative PLR was associated with worse overall survival(HR=1.51,95%CI 1.17-1.94,P=0.001),cancer specific survival(HR=1.52,95%CI 1.21-1.90,P<0.001),disease free survival(HR=1.32,95%CI 1.12-1.56,P=0.001),and progression free survival(HR=1.88,95%CI 1.41-2.52,P<0.001).Furthermore,the sensitivity analyses validated the stability and reliability of the results.Conclusion:The present meta-analysis demonstrates a significant association between elevated preoperative PLR and poor prognosis of UTUC patients treated with radical nephroureterectomy.Hence,PLR could be helpful as a potential prognostic biomarker to guide clinical decision-making and select individualized treatment strategies for UTUC patients.However,more prospective and large-scale trials are needed to provide more evidence.

Research progress in genomics associated with prognosis of upper tract urothelial carcinoma

Upper tract urothelial carcinoma and bladder urothelial carcinoma both belong to urothelial carcinoma,which is a malignant tumor occurring in the renal pelvis and ureteral urothelium.The incidence rate of UTUC is higher among Asians and it shows various pathogenic factors.Patients of UTUC have a short lifespan,and most of them have shown invasive malignant tumors at the time of initial diagnosis.The treatment of most UTUC patients is limited to surgical resection,radiotherapy and chemotherapy in clinical.Due to its rarity,the studies on targeted therapy are rare.With the development of the targeted therapy and immunotherapy,genomics exploration that affects the prognosis of UTUC becomes particularly important.In this paper,we intend to review the differential expression,clinical significance and some special types of UTUC genomes through the UTUC genome.

A Case Report: High-Grade Urothelial Carcinoma in the Renal Pelvis with Complete Kidney and Ureter Duplication Featuring Heterologous Differentiation

This report describes a considerably rare case of high-grade urothelial carcinoma of the renal pelvis and ureter,presenting with heterologous differentiation,in a patient with bilateral duplicated kidneys.A 73-year-old male experienced intermittent gross hematuria for 5 months,accompanied by lower back and abdominal pain.Ultrasound and computed tomography scans revealed bilateral renal and ureteral duplication with multiple tumors in the left renal pelvis.A total nephroterectomy and bladder cuff resection were performed on the left two nephrons.Multiple space-occupying lesions were identified in the left renal pelvis and ureter.Histopathological examination showed poorly differentiated and diverse tumor cells,manifesting as sarcomatoid carcinoma,papillary adenocarcinoma,and infiltrating high-grade urothelial carcinoma.The tumor infiltrated the subcutaneous fibrous connective tissue of the renal pelvis and the full thickness of the ureter.Given the rarity of recurrent renal urothelial carcinoma with heterogeneous differentiation,comprehensive imaging and pathological assessments are vital to delineate the nature of the lesion and the direction of tissue pathological heterologous differentiation.These evaluations guide early radical surgical interventions,improving survival rates.

Laparoscopic nephroureterectomy for upper tract urothelial carcinoma-Update

Upper urinary tract urothelial carcinomas(UTUCs)are uncommon and account for only 5%e10%of urothelial carcinomas.Pyelocaliceal tumors are about twice as common as ureteral tumors.Sixty percent of UTUCs are invasive at diagnosis.Radical nephroureterectomy,including the excision of the distal ureter and bladder cuff is standard of care for treatment of localized UTUCs,because of the high potential for recurrence,multifocality,and progression.Since first laparoscopic nephroureterectomy(LNU)was introduced by Clayman et al.in 1991 and improvement of laparoscopic technique and equipment,LNU has been reported to be equivalent to conventional open method.We reviewed the current literature of patients with UTUCs treated by LNU focusing on technical aspects,peri-operative and oncological outcomes.Laparoscopic radical nephroureterectomy offers the advantages of minimally invasive surgery without deteriorating the oncological outcome for treatment of UTUCs.Indications tend to increase as operator skills increase.Indications for laparoscopic or open nephroureterectomy are in principle the same.The basic requirement for laparoscopic surgery in UTUCs is to achieve benefits of minimal invasive surgery and maintain oncologic principles.

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.

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.

Upper tract urothelial carcinoma: Paradigm shift towards nephron sparing management

Upper tract urothelial carcinoma （UTUC） is relatively rare compared to urothelial carcinoma of the lower tract, comprising only 5%-10% of all urothelial cancers. Although both entities share histologic properties, UTUC tends to be more invasive at diagnosis and portend a worse prognosis, with a 5 year overall mortality of 23%. To date, the gold standard management of UTUC has been radical nephroureterectomy （RNU）, with nephron sparing techniques reserved for solitary kidneys or cases where the patient could not tolerate radical surgery. Limited data from these series, as well as select series where nephron-sparing endoscopic management has been offered to a broader patient base, suggest that minimally invasive, nephron sparing techniques can offer comparable oncologic and survival outcomes to RNU in appropriately selected patients. We review the current literature on the topic and discuss long term outcomes and sequelae of the gold standard treatment, RNU. We also discuss the oncologic outcomes of minimally invasive, endoscopic management of UTUC. Our goal is to provide the reader a comprehensive overview of the current state of the feld in order to inform and guide their treatment decisions.

Molecular markers of systemic therapy response in urothelial carcinoma

Identification of reliable molecular biomarkers that can complement clinical practice represents a fascinating challenge in any cancer field.Urothelial carcinoma is a very heterogeneous disease and responses to systemic therapies,and outcomes after radical cystectomy are difficult to predict.Advances in molecular biology such as next generation sequencing and whole genome or transcriptomic analysis provide promising platforms to achieve a full understanding of the biology behind the disease and can identify emerging predictive biomarkers.Moreover,the ability to categorize patients’risk of recurrence after curative treatment,or even predict benefit from a conventional or targeted therapies,represents a compelling challenge that may reshape both selection for tailored treatment and disease monitoring.Progress has been made but currently no molecular biomarkers are used in the clinical setting to predict response to systemic agents in either neoadjuvant or adjuvant settings highlighting a relevant unmet need.Here,we aim to present the emerging role of molecular biomarkers in predicting response to systemic agents in urothelial carcinoma.

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.

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.

Intravesically instilled gemcitabine-induced lung injury in a patient with invasive urothelial carcinoma: A case report

BACKGROUND Gemcitabine is a chemotherapy agent with relatively low toxicities,as a valid option for elderly patients with underlying diseases.Gemcitabine-induced pulmonary toxicities are rare and various,ranging from self-limited episodes of bronchospasm to fatal,progressive,severe,interstitial pneumonitis and respiratory failure.Intravesical gemcitabine instillations are commonly used to reduce recurrence or progression for non-muscle-invasive bladder cancer or urothelial cancer.Few severe toxicities have been reported for the intravesical instillation is assumed to be completely separated from the systemic circulation.CASE SUMMARY A 67-year-old patient received 30 cycles of intravesical gemcitabine instillation after transurethral resection and developed a 1-wk fever,cough,hemoptysis,and dyspnea.After a thorough checkup,bilateral consolidation and infiltration of the lungs were documented and a percutaneous lung biopsy confirmed organizing pneumonia after treatment with broad-spectrum empirical antibiotics failed.Tapered corticosteroids were administered,and pulmonary toxicity gradually resolved.CONCLUSION Gemcitabine-induced pulmonary toxicities present with various manifestations.In spite of the rare pulmonary involvement by the intravesical gemcitabine instillation,health care professionals who administer gemcitabine chemotherapy in this way should monitor for gemcitabine-induced pulmonary toxicities,particularly in patients with high-risk factors.

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.