scholarly journals Frequency of microsatellite instability (MSI) in upper tract urothelial carcinoma: comparison of the Bethesda panel and the Idylla MSI assay in a consecutively collected, multi-institutional cohort

2021 ◽  
pp. jclinpath-2021-207855
Author(s):  
Friederike Kullmann ◽  
Pamela L Strissel ◽  
Reiner Strick ◽  
Robert Stoehr ◽  
Markus Eckstein ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Urothelial Carcinoma ◽  
Genetic Disorder ◽  
Upper Tract Urothelial Carcinoma ◽  
Detection Methods ◽  
Upper Tract ◽  
Standard Methodology ◽  
Low Incidence ◽  
Rare Malignancy ◽  
Mmr Proteins

AimsUpper tract urothelial carcinoma (UTUC) is a rare malignancy with a poor prognosis which occurs sporadically or in few cases results from a genetic disorder called Lynch syndrome. Recently, examination of microsatellite instability (MSI) has gained importance as a biomarker: MSI tumours are associated with a better response to immunomodulative therapies. Limited data are known about the prevalence of MSI in UTUC. New detection methods using the fully automated Idylla MSI Assay facilitate analysis of increased patient numbers.MethodsWe investigated the frequency of MSI in a multi-institutional cohort of 243 consecutively collected UTUC samples using standard methodology (Bethesda panel), along with immunohistochemistry of mismatch repair (MMR) proteins. The same tumour cohort was retested using the Idylla MSI Assay by Biocartis.ResultsUsing standard methodology, 230/243 tumours were detected as microsatellite stable (MSS), 4/243 tumours as MSI and 9/243 samples as invalid. In comparison, the Idylla MSI Assay identified four additional tumours as MSS, equalling 234/243 tumours; 4/243 were classified as MSI and only 5/243 cases as invalid. At the immunohistochemical level, MSI results were supported in all available cases with a loss in MMR proteins. The overall concordance between the standard and the Idylla MSI Assay was 98.35%. Time to result differed between 3 hours for Idylla MSI Assay and 2 days with the standard methodology.ConclusionOur data indicate a low incidence rate of MSI tumours in patients with UTUC. Furthermore, our findings highlight that Idylla MSI Assay can be applied as an alternative method of MSI analysis for UTUC.

scholarly journals UGN-101 (mitomycin gel): a novel treatment for low-grade upper tract urothelial carcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592093795
Author(s):  
Andrea Kokorovic ◽  
Surena F. Matin
Keyword(s):  
Urothelial Carcinoma ◽  
Mitomycin C ◽  
Unmet Need ◽  
Invasive Disease ◽  
Upper Tract Urothelial Carcinoma ◽  
Phase Iii ◽  
Low Grade ◽  
Upper Tract ◽  
Carcinoma Of The Bladder ◽  
Rare Malignancy

Upper tract urothelial carcinoma (UTUC) is a rare malignancy. The standard treatment for localized high-risk disease is radical nephroureterectomy, which confers significant morbidity and is not appropriate for all patients. Patients harboring low-risk, non-invasive disease may be candidates for organ-sparing treatment, which includes endoscopic resection with or without intracavitary drug therapy. Successful administration of intracavitary chemotherapy to the upper tracts is impeded by rapid washout of the agent and short dwell times. This has limited the clinical utility of mitomycin C for treatment of upper tract tumors, despite the successful outcomes observed in low-grade urothelial carcinoma of the bladder. Currently, there is an unmet need for development of a technically feasible and oncologically sound intracavitary therapy for management of low-grade UTUC. UGN-101 (Jelmyto™) is a novel formulation of mitomycin C that uses a unique hydrogel designed to increase urinary dwell time, and thereby efficacy of treatment. Preclinical data demonstrated promising results regarding the safety and feasibility of this agent. Preliminary results of a phase III trial (OLYMPUS study) [ClinicalTrials.gov identifier: NCT02793128] demonstrated the efficacy of UGN-101 as a successful chemo-ablative agent for low-grade upper tract tumors. UGN-101 may represent a pivotal paradigm shift in the treatment of low-grade UTUC. Indeed, the drug has recently been granted approval by the US Food and Drug Administration as the first treatment for low-grade UTUC, which may lead to significant improvements in patient care and a long-awaited decrease in the burden of disease.

scholarly journals Upper Tract Urothelial Carcinoma: A Clinicopathologic Study Including Microsatellite Instability Analysis

2002 ◽  
Vol 15 (8) ◽  
pp. 790-797 ◽  
Author(s):  
Hagen Blaszyk ◽  
Linan Wang ◽  
Wolfgang Dietmaier ◽  
Ferdinand Hofstädter ◽  
Lawrence J. Burgart ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Urothelial Carcinoma ◽  
Upper Tract Urothelial Carcinoma ◽  
Instability Analysis ◽  
Upper Tract ◽  
Clinicopathologic Study ◽  
Microsatellite Instability Analysis

Developing a nomogram for predicting intravesical recurrence after radical nephroureterectomy: a retrospective cohort study of mainland Chinese patients

2021 ◽  
Author(s):  
Shicong Lai ◽  
Xingbo Long ◽  
Pengjie Wu ◽  
Jianyong Liu ◽  
Samuel Seery ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Cox Regression ◽  
Upper Tract Urothelial Carcinoma ◽  
Chinese Patients ◽  
Clinicopathological Parameters ◽  
Radical Nephroureterectomy ◽  
Ki 67 ◽  
Data Set ◽  
Mainland Chinese ◽  
Upper Tract

Abstract Objective To evaluate the role of Ki-67 in predicting subsequent intravesical recurrence following radical nephroureterectomy and to develop a predictive nomogram for upper tract urothelial carcinoma patients. Methods This retrospective analysis involved 489 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision. The data set was randomly split into a training cohort of 293 patients and a validation cohort of 196 patients. Immunohistochemical analysis was used to assess the immunoreactivity of the biomarker Ki-67 in the tumor tissues. A multivariable Cox regression model was utilized to identify independent intravesical recurrence predictors after radical nephroureterectomy before constructing a nomographic model. Predictive accuracy was quantified using time-dependent receiver operating characteristic curve. Decision curve analysis was performed to evaluate the clinical benefit of models. Results With a median follow-up of 54 months, intravesical recurrence developed in 28.2% of this sample (n = 137). Tumor location, multifocality, pathological T stage, surgical approach, bladder cancer history and Ki-67 expression levels were independently associated with intravesical recurrence (all P < 0.05). The full model, which intercalated Ki-67 with traditional clinicopathological parameters, outperformed both the basic model and Xylinas’ model in terms of discriminative capacity (all P < 0.05). Decision-making analysis suggests that the more comprehensive model can also improve patients’ net benefit. Conclusions This new model, which intercalates the Ki-67 biomarker with traditional clinicopathological factors, appears to be more sensitive than nomograms previously tested across mainland Chinese populations. The findings suggest that Ki-67 could be useful for determining risk-stratified surveillance protocols following radical nephroureterectomy and in generating an individualized strategy based around intravesical recurrence predictions.

Oncologic surveillance for surgically-treated high risk upper tract urothelial carcinoma

2021 ◽  
Vol 79 ◽  
pp. S1105-S1106
Author(s):  
A. Martini ◽  
C. Lonati ◽  
A. Necchi ◽  
A. Briganti ◽  
F. Montorsi ◽  
...  
Keyword(s):  
High Risk ◽  
Urothelial Carcinoma ◽  
Upper Tract Urothelial Carcinoma ◽  
Upper Tract

scholarly journals Tumor Necrosis with Adjunction of Preoperative Monocyte-to-Lymphocyte Ratio as a New Risk Stratification Marker Can Independently Predict Poor Outcomes in Upper Tract Urothelial Carcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2983
Author(s):  
Kun-Che Lin ◽  
Hau-Chern Jan ◽  
Che-Yuan Hu ◽  
Yin-Chien Ou ◽  
Yao-Lin Kao ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Tumor Necrosis ◽  
Roc Analysis ◽  
Upper Tract Urothelial Carcinoma ◽  
Postoperative Treatment ◽  
Rank Test ◽  
Prognostic Impact ◽  
Lymphocyte Ratio ◽  
Upper Tract ◽  
The Impact

Objectives: This study aimed at investigating the prognostic impact of tumor necrosis and preoperative monocyte-to-lymphocyte ratio (MLR) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods: A total of 521 patients with UTUC treated with RNU from January 2008 to June 2019 at our institution were enrolled. Histological tumor necrosis was defined as the presence of microscopic coagulative necrosis. The optimal value of MLR was determined as 0.4 by receiver operating characteristic (ROC) analysis based on cancer-specific mortality. The Kaplan–Meier method with log-rank test and Cox proportional hazards regression models were performed to evaluate the impact of tumor necrosis and MLR on overall (OS), cancer-specific (CSS), and recurrence-free survival (RFS). Furthermore, ROC analysis was used to estimate the predictive ability of potential prognostic factors for oncological outcomes. Results: Tumor necrosis was present in 106 patients (20%), which was significantly associated with tumor location, high pathological tumor stage, lymph node metastasis, high tumor grade, lymphovascular invasion, tumor size, and increased monocyte counts. On multivariate analysis, the combination of tumor necrosis and preoperative MLR was an independent prognosticator of OS, CSS, and RFS (all p < 0.05). Moreover, ROC analyses revealed the predictive accuracy of a combination of tumor necrosis and preoperative MLR for OS, CSS, and RFS with the area under the ROC curve of 0.745, 0.810, and 0.782, respectively (all p < 0.001). Conclusions: The combination of tumor necrosis and preoperative MLR can be used as an independent prognosticator in patients with UTUC after RNU. The identification of this combination could help physicians to recognize high-risk patients with unfavorable outcomes and devise more appropriate postoperative treatment plans.

Sign in / Sign up

Export Citation Format

Share Document