Invasive Urothelial Carcinoma Research Articles

PD-L1 expression in muscle invasive urothelial carcinoma: Comparison of SP142 and SP263 assay.

High-grade urothelial carcinoma has a different molecular pathway than superficial low grade urothelial carcinoma, and is characterized by genomic instability. The high tumor mutation burden leads to neoantigen formation, evoking an immune response. The immune response has been keenly studied in last two decades and programmed death ligand-1 (PDL-1) has emerged as acceptable immunohistochemical marker for assessment of response to therapy, prognostication and patient selection for immunotherapy. The targeting of PD-1 and PDL-1 by checkpoint inhibitors (CPIs) is an attractive strategy to unblock the inhibitor and induce cytotoxic cell death. However, the presence of complementary and companion diagnostic testing with multiple PDL-1 assays and platforms for various CPIs make a diagnostic quagmire. Thus, it is the need of hour to harmonize these assays. In this undertaken study we evaluated the concordance in PD-L1 expression between the two PD-L1 clones: SP263 and SP142, in treatment naïve muscle invasive bladder cancer (MIBC). We evaluated Ventana PD-L1 "SP263 and SP142" qualitative immunohistochemical assay using rabbit monoclonal anti-PD-L1 clones in evaluation of PDL-1 immunoexpression on Ventana autostainer platform. The study includes 30 muscle invasive urothelial carcinomas, with 10 of 30 having nodal metastasis. SP263 assay was statistically more sensitive than SP142 for tumor cell (TC) scoring (P = 0.0009), whereas SP142 was more sensitive for immune cell (IC) scoring (P = 0.0067). There was no statistical significant discordance for TC or IC scoring between primary tumor and metastatic lymph node. PD-L1 testing status can be done on both primary tumor and metastatic site, however in metachronous metastatic setting, testing on recent metastatic site should be preferred. The harmonization of immunoexpression between 2 PD-L1 clones could not be achieved.

Dysfunctional Voiding- Presentation of a Rare Case of Pediatric Non Muscle Invasive Urothelial Bladder Carcinoma

Bladder cancer is rare in children, with 86.8% of pediatric patients diagnosed not carrying any of the common risk factors commonly seen in adults. Here, a 16-year-old female presented to the ED with in urinary retention. A renal bladder ultrasound revealed an echogenic focus in the bladder wall. On diagnostic cystoscopy a small papillary bladder lesion was appreciated and resected. Final pathology of the bladder mass resulted as non-invasive low grade papillary urothelial carcinoma (pTa). This report demonstrates bladder cancer in the pediatric age group, and should be considered as a possible differential diagnosis in patients with dysfunctional voiding.

A case of primary renal lymphoma that was difficult to differentiate from invasive urothelial carcinoma, lymphoma-like/plasmacytoid variant

背景：今回われわれは術前尿細胞診にてリンパ腫様型/形質細胞腫型尿路上皮癌（PUC）と誤診した腎門部発生のびまん性大細胞型悪性リンパ腫（DLBCL）を経験したので，細胞所見を中心に報告する．

POSC56 Healthcare Resource Use (HCRU), Cost Inputs, and Cost-Effectiveness Analysis (CEA) for Patients with Muscle Invasive Urothelial Carcinoma (MIUC) Treated with Radical Resection (RR): A Systematic Literature Review (SLR)

POSC56 Healthcare Resource Use (HCRU), Cost Inputs, and Cost-Effectiveness Analysis (CEA) for Patients with Muscle Invasive Urothelial Carcinoma (MIUC) Treated with Radical Resection (RR): A Systematic Literature Review (SLR)

POSB8 Efficacy and Safety Results from Randomized Controlled Trials (RCTS) Evaluating Adjuvant Treatment after Radical Resection (RR) of Muscle Invasive Urothelial Carcinoma (MIUC): A Systematic Literature Review (SLR)

POSB8 Efficacy and Safety Results from Randomized Controlled Trials (RCTS) Evaluating Adjuvant Treatment after Radical Resection (RR) of Muscle Invasive Urothelial Carcinoma (MIUC): A Systematic Literature Review (SLR)

A New Era in the Management of Tumors in Dogs Based on Liquid Biopsy

The naturally occurring high-grade invasive transitional cell carcinoma or canine invasive urothelial carcinoma localized in bladder can be successfully treated surgically, however, at time of your diagnosis, it may present itself at an advanced stage, and distant metastases occur in 50% of cases. The urothelial carcinoma has a poor prognosis due to its muscle-invasive nature and high degree of metastases to regional lymph nodes or distant organs

POSC6 Efficacy and Safety Results from Real-World Studies Evaluating Adjuvant Treatment after Radical Resection (RR) of Muscle Invasive Urothelial Carcinoma (MIUC): A Systematic Literature Review (SLR)

POSC6 Efficacy and Safety Results from Real-World Studies Evaluating Adjuvant Treatment after Radical Resection (RR) of Muscle Invasive Urothelial Carcinoma (MIUC): A Systematic Literature Review (SLR)

POSA342 Reported Utilities and Health-Related Quality of Life (HRQOL) Data for Patients with Muscle Invasive Urothelial Carcinoma (MIUC) Treated with Radical Resection (RR): A Systematic Literature Review (SLR)

POSA342 Reported Utilities and Health-Related Quality of Life (HRQOL) Data for Patients with Muscle Invasive Urothelial Carcinoma (MIUC) Treated with Radical Resection (RR): A Systematic Literature Review (SLR)

Machine Learning Quantification of Tumor-Stroma Ratio in Early Muscle Invasive Urothelial Carcinomas

Machine Learning Quantification of Tumor-Stroma Ratio in Early Muscle Invasive Urothelial Carcinomas

Network Pharmacology-Based Study on the Active Component and Mechanism of the Anti-Non-Invasive and Invasive Bladder Urothelial Carcinoma Effects of Zhuling Jisheng Decoction.

Zhuling Jisheng decoction is employed for the treatment of bladder urothelial cancer in clinical practice of traditional Chinese medicine. However, there are few studies on its precise mechanism. For the antibladder cancer action of Zhuling Jisheng decoction, a network pharmacological technique was used to design a component/target/pathway molecular regulatory network. The TCMSP dataset was used to identify the chemical makeup of Zhuling Jisheng decoction, which was then analyzed and assessed for oral bioavailability and pharmacological similarity. The chemical composition of Zhuling Jisheng decoction was identified through the TCMSP database, and it was evaluated and screened based on oral bioavailability and drug similarity. The GEO database was searched for genes associated with urothelial bladder carcinoma, and gene targets associated with bladder urothelial cancer resistance were chosen by comparison. The function and linked pathways of the target genes were examined and screened using annotation, visualization, and a comprehensive discovery database. The impact of Zhuling Jisheng decoction on urothelial bladder cancer was studied using Cytoscape software to create a component/target/pathway network. Finally, 69 and 55 target genes were discovered for noninvasive bladder urothelial cancer and invasive bladder urothelial cancer, respectively. In noninvasive urothelial cancer, 118 pathways were highly enriched, including the TNF signaling pathway and the IL-17 signaling route. 103 pathways were highly enriched in invasive urothelial cancer, including the p53 signaling route, bladder cancer route, and calcium signaling route. There were 18 and 15 drug targets associated with noninvasive and invasive bladder urothelial carcinoma prognoses. Many signaling pathways directly act on tumours, and indirect pathways inhibit the development of bladder urothelial carcinoma. This research establishes a scientific foundation for further research into the framework of action of Zhuling Jisheng decoction in the therapy of bladder urothelial cancer.

Extramammary Paget Disease of Peristomal Skin Secondary to Bladder Urothelial Carcinoma

An 87-year-old man with history of invasive transitional cell urothelial carcinoma of the bladder and left distal ureter status-post radical cystoprostatectomy and left distal uretectomy with uretero-ureterostomy and ileal conduit urinary diversion 14 years prior presented to our dermatology clinic with complaint of peristomal rash for many years. The patient reported the rash had been present for at least 5 years and was getting larger. It was described as pruritic and tender.

Non-muscle invasive micropapillary urothelial carcinoma of the bladder: Variable use of initial cystectomy versus intravesical bacillus calmette-guérin

Introduction and Objective Micropapillary urothelial carcinoma (MPUC) is a rare and aggressive histologic variant of bladder cancer. Treatment guidelines recommend forgoing Bacillus Calmette-Guérin (BCG) therapy in favor of early radical cystectomy for non-muscle invasive (NMI)-MPUC due to high rates of disease progression. We aimed to evaluate its management in patients with immediate cystectomy and BCG across various centers. Methods Patients with MPUC were identified from the National Cancer Database (2004-2017). Treatment trends and rates of pathological upstaging were identified. Bivariate and multivariate analyses were performed to assess differences in outcomes by treatment approach. Results 1,685 patients were diagnosed with MPUC during the study period with 531 identified with localized Ta, T1, or Tis disease. BCG was administered as an initial therapy in 24.1% of NMI-MPBC patients and in 16.3% of NMI-non-MPUC patients (p<0.001). Cystectomy was performed as primary therapy for NMI disease in 29.9% of MPUC and in 2.7% of non-MPUC patients (p<0.001). Of the patients who underwent primary cystectomy, upstaging from NMI-MPUC to T2-T4 disease was seen in 46.5% of the MPUC patients compared to 37.3% in patients with non-MPUC (p=0.025). Upstaging to pathologic N1-3 disease was observed in 33.1% of MPUC patients compared to 11.9% non-MPUC patients (p<0.001). Cox regression analysis, adjusting for patient age, sex, race, comorbidities, and disease stage, care at academic cancer centers were associated with increased odds of having cystectomy as primary therapy compared to community cancer centers (OR = 4.29, 95% CI 2.73-6.76). Conclusion The current study lends evidence to current practice guidelines by reporting treatment patterns for patients with micropapillary bladder cancer across a broad spectrum of clinical practice. NMI-MPUC patients treated at academic cancer centers were more likely to receive radical surgery as primary treatment compared to patients at the community cancer centers.

Non-muscle invasive micropapillary urothelial carcinoma of the bladder: Variable use of initial cystectomy versus intravesical bacillus calmette-guérin

Introduction and Objective Micropapillary urothelial carcinoma (MPUC) is a rare and aggressive histologic variant of bladder cancer. Treatment guidelines recommend forgoing Bacillus Calmette-Guérin (BCG) therapy in favor of early radical cystectomy for non-muscle invasive (NMI)-MPUC due to high rates of disease progression. We aimed to evaluate its management in patients with immediate cystectomy and BCG across various centers. Methods Patients with MPUC were identified from the National Cancer Database (2004-2017). Treatment trends and rates of pathological upstaging were identified. Bivariate and multivariate analyses were performed to assess differences in outcomes by treatment approach. Results 1,685 patients were diagnosed with MPUC during the study period with 531 identified with localized Ta, T1, or Tis disease. BCG was administered as an initial therapy in 24.1% of NMI-MPBC patients and in 16.3% of NMI-non-MPUC patients (p<0.001). Cystectomy was performed as primary therapy for NMI disease in 29.9% of MPUC and in 2.7% of non-MPUC patients (p<0.001). Of the patients who underwent primary cystectomy, upstaging from NMI-MPUC to T2-T4 disease was seen in 46.5% of the MPUC patients compared to 37.3% in patients with non-MPUC (p=0.025). Upstaging to pathologic N1-3 disease was observed in 33.1% of MPUC patients compared to 11.9% non-MPUC patients (p<0.001). Cox regression analysis, adjusting for patient age, sex, race, comorbidities, and disease stage, care at academic cancer centers were associated with increased odds of having cystectomy as primary therapy compared to community cancer centers (OR = 4.29, 95% CI 2.73-6.76). Conclusion The current study lends evidence to current practice guidelines by reporting treatment patterns for patients with micropapillary bladder cancer across a broad spectrum of clinical practice. NMI-MPUC patients treated at academic cancer centers were more likely to receive radical surgery as primary treatment compared to patients at the community cancer centers.

A Nomogram Model to Predict Recurrence of Non-Muscle Invasive Bladder Urothelial Carcinoma After Resection Based on Clinical Parameters and Immunohistochemical Markers

Objective This study aims to establish a nomogram model by combining traditional clinical parameters with immunohistochemical markers to predict the recurrence of non-muscle invasive bladder urothelial carcinoma (NMIBUC) after resection. Methods In total, 504 patients were included in this study. Of these patients, 353 underwent transurethral resection of bladder tumor (TURBT) in the Yongchuan Hospital of Chongqing Medical University and were identified as a training cohort. Univariate and multivariate Cox regression analyses were used to determine the risk factors associated with recurrence in the training cohort and to establish a nomogram model. A total of 151 patients who were hospitalized in the Second Affiliated Hospital of Chongqing Medical University (validation cohort) were used for further validation. The calibration curve was generated for internal and external model validation. The clinical practicability of this model was further verified by comparing the consistency index (C-index) among various models. Results The mean follow-up time of the training cohort was 45.6 months (range 4–90). In total, 146 patients relapsed in training cohort. After univariate analysis, multivariate analysis further confirmed tumor grade (p=.034), immediate postoperative instillation therapy (p=.025), Ki67 (p=.047), P53 (p=.038) and CK20 (p=.049) as independent risk factors for recurrence, and these factors were included in the nomogram model. The model more accurately predicted recurrence compared with other models based on the highest C-index of 0.82 (95% CI, 0.78–0.86) in the training cohort and 0.80 (95% CI, 0.77–0.83) in the validation cohort. Conclusions This proposed nomogram model based on traditional clinical parameters and immunohistochemical markers can more accurately predict postoperative recurrence in patients with NMIBUC.

Prognostic and Diagnostic Significance of Platelet Indices in Patients with Urothelial Carcinoma

Some prognostic markers have been shown to determine the course and survival of Urothelial Cancer. A cross-sectional retrospective study, specifically looking at the role that various indices related to platelets—namely Mean Platelet Volume (MPV), platelet count and MPV/Platelet ratio—play in the diagnosis and prognosis of urinary bladder cancer, was conducted at the Department of Pathology, Geetanjali Medical College and Hospital, Udaipur, Rajasthan (India) between January 2016 and August 2021 and included 76 patients who underwent multicore TURBT biopsy. Complete Blood Count (CBC) was used to determine platelet count, MPV and MPV/Platelet ratio. Platelet count was found to be more elevated in patients with high grade urothelial carcinoma and muscle invasive urothelial carcinoma as compared to patients with low grade urothelial carcinoma and non-muscle invasive urothelial carcinoma (p < 0.05). The median MPV and MPV/PLT ratio was found to be significantly lower in patients with high grade urothelial carcinoma and muscle invasive urothelial carcinoma as compared to patients with low grade urothelial carcinoma and non-muscle invasive urothelial carcinoma (p < 0.05). Thus, platelet indices can be useful supportive prognostic and diagnostic indicators in the determination of the clinical outcome of urothelial carcinoma.

Malignant Central Nervous System Lymphoma after Radical Total Cystectomy : A Diagnostic Challenge

We report a case of primary central nervous system lymphoma (PCNSL) in an 81-year-old man who had undergone radical cystectomy with an ileal conduit urostomy due to a diagnosis of muscle-invasive bladder cancer. The postoperative diagnosis was invasive urothelial carcinoma (pT2bN1M0, stage IV). Gemcitabine-cisplatin therapy was provided as adjuvant chemotherapy, and there was no recurrence during follow-up. Four years after surgery, he visited the emergency department because of weakness of the lower extremities and stuttering. He was found to have a parietal lobe mass on magnetic resonance imaging (MRI) and hospitalized with suspicion of brain metastasis. Despite examination by a neurosurgeon, it was not possible to make a clinical diagnosis, and the patient gradually deteriorated and died 21 days later. The pathology results were diagnostic of PCNSL.

Medical Image Diagnostic Value of Computed Tomography for Bladder Tumors.

Objective To study computed tomography (CT) imaging characteristics of bladder tumors, to explore the value of CT in tumor diagnosis, and to identify the relevant factors of CT missed diagnosis so that medical staff can be more accurate in the diagnosis of bladder tumors. Methods To retrospectively analyze the CT manifestations of 153 bladder tumor cases confirmed by paraffin pathology in our hospital and to study the difference between the benign and CT imaging features. CT indicators mainly include the number, location, morphology, calcification, bladder wall smoothness, CT value, degree of enhancement, and invasion of surrounding tissues and organs. Then, we retrospectively analyze 17 cases of CT missed diagnosis of bladder tumors, analyze related factors, and discuss the role of CT in the diagnosis of bladder tumors. Results This study has shown that with the help of CT images, the diagnosis rate of bladder tumors has been greatly improved. Of the 153 patients studied, noninvasive urothelial carcinoma accounted for 18.95% of all benign and malignant bladder tumors, invasive urothelial carcinoma accounted for 67.93%, prostatic metastatic carcinoma and inflammatory myofibroblastoma accounted for 8.47%, pheochromocytoma accounted for 1.31%, inverted papilloma accounted for 1.31%, tubular choriocarcinoma accounted for 0.63%, and endocystitis accounted for 1.31%. In addition, the blood supply level, CT index bladder wall smoothness, and CT value are also statistically significant (P < 0.05). Conclusions CT is of high value in the diagnosis of bladder tumors, and benign and malignant bladder tumors have CT and CT imaging features. The size of bladder tumors is related to the missed diagnosis rate of CT. The application of CT examination technology can improve the accuracy of diagnosis of bladder tumors.

(Pro)renin Receptor Is a Novel Independent Prognostic Marker in Invasive Urothelial Carcinoma of the Bladder.

Simple SummaryThis is a novel description of (Pro)renin receptor (PRR) protein and its prognostic role in invasive urothelial cancer of the bladder. Using a tissue microarray, we investigated PRR expression and other immunohistochemical markers including p53, immune-checkpoint inhibition, and basal and luminal phenotypes in a series of patients with invasive urothelial carcinoma of the bladder treated with radical cystectomy. PRR expression is an independent prognostic marker and could be a potential target in urothelial carcinoma that should be further investigated.(Pro)renin receptor (PRR) is being investigated in several malignancies as it activates pathogenic pathways that contribute to cell proliferation, immunosuppressive microenvironments, and acquisition of aggressive neoplastic phenotypes. Its implication in urothelial cancer (UC) has not been evaluated so far. We retrospectively evaluate the prognostic role of PRR expression in a series of patients with invasive UC treated with radical cystectomy and other clinical and histopathological parameters including p53, markers of immune-checkpoint inhibition, and basal and luminal phenotypes evaluated by tissue microarray. Cox regression analyses using stepwise selection evaluated candidate prognostic factors and disease-specific survival. PRR was expressed in 77.3% of the primary tumors and in 70% of positive lymph nodes. PRR expression correlated with age (p = 0.006) and was associated with lower preoperatively hemoglobin levels. No other statistical association was evidenced with clinical and pathological variables (gender, ASA score, Charlson comorbidity index, grade, pT, pN) or immunohistochemical expressions evaluated (CK20, GA-TA3, CK5/6, CD44, PD-L1, PD-1, B7-H3, VISTA, and p53). PRR expression in primary tumors was associated with worse survival (log-rank, p = 0.008). Cox regression revealed that PRR expression (HR 1.85, 95% CI 1.22–2.8), pT (HR 7.02, 95% CI 2.68–18.39), pN (HR 2.3, 95% CI 1.27–4.19), and p53 expression (HR 1.95, 95% CI 1.1–3.45) were independent prognostic factors in this series. In conclusion, we describe PRR protein and its prognostic role in invasive UC for the first time. Likely mechanisms involved are MAPK/ERK activation, Wnt/β-catenin signaling, and v-ATPAse function.

Management Trends and Outcomes of Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder: Evolution of the University of Southern California Experience over 3,347 Cases.

There are conflicting reports on outcome trends following radical cystectomy (RC) for bladder cancer. Evolution of modern bladder cancer management and its impact on outcomes was analyzed using a longitudinal cohort of 3,347 patients who underwent RC at an academic center between 1971 and 2018. Outcomes included recurrence-free survival (RFS) and overall survival (OS). Associations were assessed using univariable and multivariable models. In all, 70.9% of cases underwent open RC in the last decade, although trend for robot-assisted RC rose since 2009. While lymphadenectomy template remained consistent, nodal submission changed to anatomical packets in 2002 with increase in yield (p <0.001). Neoadjuvant chemotherapy (NAC) use increased with time with concomitant decrease in adjuvant chemotherapy; this was notable in the last decade (p <0.001) and coincided with improved pT0N0M0 rate (p=0.013). Median 5-year RFS and OS probabilities were 65% and 55%, respectively. Advanced stage, NAC, delay to RC, lymphovascular invasion and positive margins were associated with worse RFS (all, multivariable p <0.001). RFS remained stable over time (p=0.73) but OS improved (5-year probability, 1990-1999 51%, 2010-2018 62%; p=0.019). Among patients with extravesical and/or node-positive disease, those who received NAC had worse outcomes than those who directly underwent RC (p ≤0.001). Despite perioperative and surgical advances, and improved pT0N0M0 rates, there has been no overall change in RFS trend following RC, although OS rates have improved. While patients who are downstaged with NAC derive great benefit, our real-world experience highlights the importance of preemptively identifying NAC nonresponders who may have worse post-RC outcomes.

P124 - A randomized, double-blind, placebo-controlled, phase 3 trial of infigratinib as adjuvant therapy in patients with invasive urothelial carcinoma harboring susceptible FGFR3 genetic alterations: PROOF 302

P124 - A randomized, double-blind, placebo-controlled, phase 3 trial of infigratinib as adjuvant therapy in patients with invasive urothelial carcinoma harboring susceptible FGFR3 genetic alterations: PROOF 302