scholarly journals A urine-based DNA methylation assay to facilitate early detection and risk stratification of bladder cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Weimei Ruan ◽  
Xu Chen ◽  
Ming Huang ◽  
Hong Wang ◽  
Jiaxin Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
Risk Stratification ◽  
Early Stage ◽  
Operative Risk ◽  
Low Grade ◽  
Single Center ◽  
Detection Model ◽  
Methylation Assay ◽  
Muscle Invasive

Abstract Background Current non-invasive tests have limited sensitivities and lack capabilities of pre-operative risk stratification for bladder cancer (BC) diagnosis. We aimed to develop and validate a urine-based DNA methylation assay as a clinically feasible test for improving BC detection and enabling pre-operative risk stratifications. Methods A urine-based DNA methylation assay was developed and validated by retrospective single-center studies in patients of suspected BC in Cohort 1 (n = 192) and Cohort 2 (n = 98), respectively. In addition, a prospective single-center study in hematuria patient group (Cohort 3, n = 174) was used as a second validation of the model. Results The assay with a dual-marker detection model showed 88.1% and 91.2% sensitivities, 89.7% and 85.7% specificities in validation Cohort 2 (patients of suspected BC) and Cohort 3 (patients of hematuria), respectively. Furthermore, this assay showed improved sensitivities over cytology and FISH on detecting low-grade tumor (66.7–77.8% vs. 0.0–22.2%, 0.0–22.2%), Ta tumor (83.3% vs. 22.2–41.2%, 44.4–52.9%) and non-muscle invasive BC (NMIBC) (80.0–89.7% vs. 51.5–52.0%, 59.4–72.0%) in both cohorts. The assay also had higher accuracies (88.9–95.8%) in diagnosing cases with concurrent genitourinary disorders as compared to cytology (55.6–70.8%) and FISH (72.2–77.8%). Meanwhile, the assay with a five-marker stratification model identified high-risk NMIBC and muscle invasive BC with 90.5% sensitivity and 86.8% specificity in Cohort 2. Conclusions The urine-based DNA methylation assay represents a highly sensitive and specific approach for BC early-stage detection and risk stratification. It has a potential to be used as a routine test to improve diagnosis and prognosis of BC in clinic.

Microfluidic Assaying of Circulating Tumor Cells and its Correlation with Muscle Invasiveness and Tumor Grade of Urothelial Bladder Cancer

2021 ◽  
Author(s):  
Guanghou Fu ◽  
Kok Suen Cheng ◽  
Anqi Chen ◽  
Zhijie Xu ◽  
Xiaoyi Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Risk Stratification ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Tumor Grade ◽  
Invasive Bladder Cancer ◽  
Low Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Abstract Background: Bladder cancer is characterized by its frequent recurrence and progression. Effective treatment strategies need to be based on an accurate risk stratification, in which muscle invasiveness and tumor grade represent the two most important factors. Traditional imaging techniques provide preliminary information about muscle invasiveness but are lacking in terms of accuracy. Although as the gold standard, pathological biopsy is only available after the surgery and cannot be performed longitudinally for long-term surveillance. Methods: In this work, we developed a microfluidic approach that interrogates circulating tumor cells (CTCs) in the peripheral blood of bladder cancer patients to reflect the risk stratification of the disease. Results：In a cohort of 48 bladder cancer patients comprising 33 non-muscle invasive bladder cancer (NMIBC) cases and 15 muscle invasive bladder cancer (MIBC) cases, the CTC count was found to be considerably higher in the MIBC group compared with the NMIBC group (4.67 vs. 1.88 CTCs/3 mL, P=0.019), and was significantly higher in high-grade bladder cancer patients verses low-grade bladder cancer patients (3.69 vs. 1.18 CTCs/3mL, P=0.024). Conclusions: This microfluidic assay of CTCs is believed to be a promising complementary tool for the risk stratification of bladder cancer.Trial registration: This research was conducted under the approval of the Ethics Committee of the First Affiliated Hospital at Zhejiang University School of Medicine with the Registration No. 2015-218.

scholarly journals Microfluidic Assaying of Circulating Tumor Cells and Its Application in Risk Stratification of Urothelial Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Guanghou Fu ◽  
Kok Suen Cheng ◽  
Anqi Chen ◽  
Zhijie Xu ◽  
Xiaoyi Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Risk Stratification ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Imaging Techniques ◽  
Invasive Bladder Cancer ◽  
Low Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Bladder cancer is characterized by its frequent recurrence and progression. Effective treatment strategies need to be based on an accurate risk stratification, in which muscle invasiveness and tumor grade represent the two most important factors. Traditional imaging techniques provide preliminary information about muscle invasiveness but are lacking in terms of accuracy. Although as the gold standard, pathological biopsy is only available after the surgery and cannot be performed longitudinally for long-term surveillance. In this work, we developed a microfluidic approach that interrogates circulating tumor cells (CTCs) in the peripheral blood of bladder cancer patients to reflect the risk stratification of the disease. In a cohort of 48 bladder cancer patients comprising 33 non-muscle invasive bladder cancer (NMIBC) cases and 15 muscle invasive bladder cancer (MIBC) cases, the CTC count was found to be considerably higher in the MIBC group compared with the NMIBC group (4.67 vs. 1.88 CTCs/3 mL, P=0.019), and was significantly higher in high-grade bladder cancer patients verses low-grade bladder cancer patients (3.69 vs. 1.18 CTCs/3mL, P=0.024). This microfluidic assay of CTCs is believed to be a promising complementary tool for the risk stratification of bladder cancer.

scholarly journals Imaging of Bladder Cancer: Standard Applications and Future Trends

Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 220
Author(s):  
Rasha Taha Abouelkheir ◽  
Abdalla Abdelhamid ◽  
Mohamed Abou El-Ghar ◽  
Tarek El-Diasty
Keyword(s):  
Bladder Cancer ◽  
Malignant Tumors ◽  
Cancer Staging ◽  
Low Grade ◽  
Diagnostic Modality ◽  
Positron Emission ◽  
Standard Application ◽  
Muscle Invasive ◽  
Muscle Invasion ◽  
Low Sensitivity

The evolution in imaging has had an increasing role in the diagnosis, staging and follow up of bladder cancer. Conventional cystoscopy is crucial in the diagnosis of bladder cancer. However, a cystoscopic procedure cannot always depict carcinoma in situ (CIS) or differentiate benign from malignant tumors prior to biopsy. This review will discuss the standard application, novel imaging modalities and their additive role in patients with bladder cancer. Staging can be performed with CT, but distinguishing between T1 and T2 BCa (bladder cancer) cannot be assessed. MRI can distinguish muscle-invasive from non-muscle-invasive tumors with accurate local staging. Vesical Imaging-Reporting and Data System (VI-RADS) score is a new diagnostic modality used for the prediction of tumor aggressiveness and therapeutic response. Bone scintigraphy is recommended in patients with muscle-invasive BCa with suspected bony metastases. CT shows low sensitivity for nodal staging; however, PET (Positron Emission Tomography)/CT is superior and highly recommended for restaging and determining therapeutic effect. PET/MRI is a new imaging technique in bladder cancer imaging and its role is promising. Texture analysis has shown significant steps in discriminating low-grade from high-grade bladder cancer. Radiomics could be a reliable method for quantitative assessment of the muscle invasion of bladder cancer.

Development and Validation of a Prognostic Nomogram Model for Recurrence of Non-Muscle Invasive Bladder Cancer

2021 ◽  
Author(s):  
Sanhe Liu ◽  
Yongzhi Li ◽  
Diansheng Cui ◽  
Yuexia Jiao ◽  
Liqun Duan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Risk Stratification ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Muscle Invasive Bladder Cancer ◽  
Clinicopathologic Characteristics ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Muscle Invasive

Abstract BackgroundDifferent recurrence probability of non-muscle invasive bladder cancer (NMIBC) requests different adjuvant treatments and follow-up strategies. However, there is no simple, intuitive, and generally accepted clinical recurrence predictive model available for NMIBC. This study aims to construct a predictive model for the recurrence of NMIBC based on demographics and clinicopathologic characteristics from two independent centers. MethodsDemographics and clinicopathologic characteristics of 511 patients with NMIBC were retrospectively collected. Recurrence free survival (RFS) was estimated using the Kaplan-Meier method and log-rank tests. Univariate Cox proportional hazards regression analysis was used to screen variables associated with RFS, and a multivariate Cox proportional hazards regression model with a stepwise procedure was used to identify those factors of significance. A final nomogram model was built using the multivariable Cox method. The performance of the nomogram model was evaluated with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed with bootstrap resampling. X-tile software was used for risk stratification calculated by the nomogram model. ResultsIndependent prognostic factors including tumor stage, recurrence status, and European Association of Urology (EAU) risk stratification group were introduced to the nomogram model. The model showed acceptable calibration and discrimination (area under the receiver operating characteristic [ROC] curve was 0.85; the consistency index [C-index] was 0.79 [95% CI: 0.76 to 0.82]), which was superior to the EAU risk stratification group alone. The decision curve also proved well clinical usefulness. Moreover, all populations could be stratified into three distinct risk groups by the nomogram model. ConclusionsWe established and validated a novel nomogram model that can provide individual prediction of RFS for patients with NMIBC. This intuitively prognostic nomogram model may help clinicians in postoperative treatment and follow-up decision-making.

Integrated clinicopathologic and molecular risk stratification for disease recurrence in muscle-invasive bladder cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 490-490
Author(s):  
Ruben Carmona ◽  
Alan Pollack ◽  
Zachary L Smith ◽  
Jeff M. Michalski ◽  
Hiram Alberto Gay ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Risk Stratification ◽  
Molecular Subtype ◽  
Disease Recurrence ◽  
Invasive Bladder Cancer ◽  
Training Set ◽  
Combined Model ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive ◽  
Testing Set

490 Background: Integrating molecular subtypes, gene transcripts associated with disease recurrence (DR), and clinicopathologic features may help risk stratify muscle-invasive bladder cancer (MIBC) patients & guide therapy selection. We hypothesized that combined transcriptomic & clinical data would improve risk stratification for DR (local or distant) after cystectomy +/- adjuvant chemotherapy. Methods: We identified 401 MIBC patients (pT2-4 N0-N3 M0) in The Cancer Genome Atlas with detailed demographic, clinical, pathologic, and treatment-related data. We split the data into training (60%) & testing (40%) sets. We produced RNA gene expression scores for molecular subtype using 48 established, relevant genes (PMID 28988769). In the training set, we performed feature selection by conducting random forest modeling of an additional 108 genes associated with DR. We kept genes of highest importance based on the evaluation of increasing mean-squared error & node purity. We excluded highly correlated genes & used the false discovery rate method for multiple hypotheses testing. We performed univariable analyses on genes of highest importance, molecular subtype, & clinicopathologic variables. Using adjusted multivariable analyses (MVA), we built two models: with & without transcriptomic data. Using the testing set, we compared the final models' performance to predict DR, using receiver operating characteristics & area under the curve (AUC). Results: Median follow-up was 18 months (range 1-168). 104 patients recurred with a 5-yr cumulative incidence of 34.6%[28.6-40.5%]. Using the training set, we identified 6 genes significantly associated with DR (VEGFA, TRMT1, FGFR2B, ERBB2, MMP14, PDGFC). The final MVA showed that the new 6-gene signature (HR 1.61, 95% CI 1.27-2.05, p < 0.001); immune molecular subtype [increased expression of PD-L1, PD-1, IDO1, CXCL11, L1CAM, SAA1] (HR 0.52, 95% CI 0.29-0.94, p = 0.03); smoking status (HR 1.17 per 10 pack-years, 95% CI 1.05-1.29, p = 0.005); and local failure risk factors [≥pT3 with negative margins & ≥10 nodes removed (HR 1.63, 95% CI 1.15-2.32, p = 0.006); ≥pT3 and positive margins OR < 10 nodes removed (HR 3.26, 95%CI 2.43 to 4.09, p = 0.007)], were all significantly associated with DR. This combined model outperformed a stand-alone clinicopathologic model (AUC 0.75 vs. 0.66) in the testing set. The combined model stratified patients based on DR risk into 3 groups with 5-yr cumulative incidences of 19.8%[7.7-31.9%] (low-risk); 34.5%[26.1-42.8%] (intermediate); and 49.8%[37.7-61.9%] (high), Gray’s Test p < 0.0001. Conclusions: To our knowledge, this study is the first to integrate clinicopathologic & transcriptomic information (including molecular subtype) to better stratify MIBC patients by risk of recurrence. This stratification may help guide decision-making for adjuvant treatment. Further validation is warranted.

scholarly journals MicroRNAs Which Can Prognosticate Aggressiveness of Bladder Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1551 ◽  
Author(s):  
Edyta Marta Borkowska ◽  
Tomasz Konecki ◽  
Michał Pietrusiński ◽  
Maciej Borowiec ◽  
Zbigniew Jabłonowski
Keyword(s):  
Bladder Cancer ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Control Group ◽  
Low Grade ◽  
Operating Characteristics ◽  
High Death Rate ◽  
Biological Potential ◽  
High Death ◽  
Muscle Invasive

Bladder cancer (BC) is still characterized by a very high death rate in patients with this disease. One of the reasons for this is the lack of adequate markers which could help determine the biological potential of the tumor to develop into its invasive stage. It has been found that some microRNAs (miRNAs) correlate with disease progression. The purpose of this study was to identify which miRNAs can accurately predict the presence of BC and can differentiate low grade (LG) tumors from high grade (HG) tumors. The study included 55 patients with diagnosed bladder cancer and 30 persons belonging to the control group. The expression of seven selected miRNAs was estimated with the real-time PCR technique according to miR-103-5p (for the normalization of the results). Receiver operating characteristics (ROC) curves and the area under the curve (AUC) were used to evaluate the feasibility of using selected markers as biomarkers for detecting BC and discriminating non-muscle invasive BC (NMIBC) from muscle invasive BC (MIBC). For HG tumors, the relevant classifiers are miR-205-5p and miR-20a-5p, whereas miR-205-5p and miR-182-5p are for LG (AUC = 0.964 and AUC = 0.992, respectively). NMIBC patients with LG disease are characterized by significantly higher miR-130b-3p expression values compared to patients in HG tumors.

scholarly journals Validation of EORTC, CUETO and EAU risk stratification in prediction of recurrence, progression and death of patients with initially non-muscle invasive bladder cancer (NMIBC): a cohort analysis with systematic review.

2019 ◽  
Author(s):  
Mateusz Jobczyk ◽  
Konrad Stawiski ◽  
Wojciech Fendler ◽  
Waldemar Różański
Keyword(s):  
Bladder Cancer ◽  
Risk Stratification ◽  
Cohort Analysis ◽  
Risk Groups ◽  
Invasive Bladder Cancer ◽  
Sufficient Evidence ◽  
Current Evidence ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive ◽  
Better Than

Abstract Purpose: To validate and summarize current evidence about the reliability of EORTC, CUETO and EAU risk stratification in prediction of recurrence, progression and death of patients with initially non-muscle-invasive bladder cancer (NMIBC).Methods: Retrospective cohort analysis of 322 patients with newly diagnosed NMIBC. We assessed the concordance (Harrell's c-index) of our results with calculated risk scores in Cox proportional hazard regression models and utilized receiver operating characteristic curve analysis (area under curve; AUCROC). Lastly, to further confirm our observations we conducted a systematic reviewResults: 1-year and 5-year c-indices ranged from 0.55 to 0.66 for recurrence and from 0.72 to 0.82 for progression. AUCROC of predictions ranged from 0.46 for 1-year recurrence risk based on CUETO groups to 0.82 for 1-year progression risk based on EAU risk groups. The accuracy of prediction was lower for patients treated with BCG maintenance immunotherapy. EORTC model (overall c-index c=0.64; 95%CI:0.61-0.68) was superior to EAU (p=0.035; 0.62; 95%CI: 0.59-0.66) and CUETO (p<0.001; c=0.53; 95%CI:0.50-0.56) model in recurrence prediction. EORTC model (c=0.82; 95%CI:0.77-0.86) also performed better than CUETO (p=0.008; c=0.73; 95%CI:0.66-0.81) but there was no sufficient evidence that it performed better than EAU (p=0.572; c=0.81; 95%CI:0.77-0.84) for predicting progression. EORTC and CUETO comparably predicted progression in BCG-treated EAU high-risk patients (p=0.48).Conclusions: The division into risk groups by EORTC, CUETO and EAU offered moderately accurate predictions about recurrence and progression of NMIBC, which emphasizes the urgent need for the development of more personalized and accurate predictive tool. EORTC provided the best recurrence and progression prediction.

Sign in / Sign up

Export Citation Format

Share Document