Diagnosis Of Bladder Cancer In Patients Research Articles

Evaluation of Sensitive Urine DNA-Based PENK Methylation Test for Detecting Bladder Cancer in Patients with Hematuria

Hematuria is a prevalent symptom associated with bladder cancer (BC). However, the invasiveness and cost of cystoscopy, the current gold standard for BC diagnosis in patients with hematuria, necessitate the development of a sensitive and accurate noninvasive test. This study introduces and validates a highly sensitive urine-based DNA methylation test. The test improves sensitivity in detecting PENK methylation in urine DNA using linear target enrichment followed by quantitative methylation-specific PCR. In a case-control study comprising 175 patients with BC and 143 patients without BC with hematuria, the test's optimal cutoff value was determined by distinguishing between two groups, achieved an overall sensitivity of 86.9% and a specificity of 91.6%, with an area under the curve of 0.892. A prospective validation clinical study involving 366 patients with hematuria scheduled for cystoscopy assessed the test's performance. The test demonstrated an overall sensitivity of 84.2% in detecting 38 cases of BC, a specificity of 95.7%, and an area under the curve of 0.900. Notably, the sensitivity for detecting Ta high grade and higher stages of BC reached 92.3%. The test's negative predictive value was 98.2%, and the positive predictive value was 68.7%. These findings highlight the potential of the PENK methylation in urine DNA using linear target enrichment followed by quantitative methylation-specific PCR test in urine as a promising molecular diagnostic tool for detecting primary BC in patients with hematuria, which may reduce the need for cystoscopy.

Abstract 5136: Bladder cancer diagnostic algorithms in hematuria populations.

Abstract Queens University Belfast, the Belfast Health Trust and Randox Laboratories are working together to create risk and diagnostic classifiers for patients with haematuria. Biomarker profiles may fail to differentiate between all possible causes of hematuria, but it would be a huge advancement if benign and malignant causes were differentiated. Our objective was to determine whether single biomarkers or multivariate algorithms could significantly improve on the predictive power of an algorithm based on demographics for detection of urothelial cancer in patients presenting with hematuria. We collected demographic and clinical information from 157 patients (80 urothelial cancers and 77 with confounding pathologies) who had presented with hematuria and were recruited to a case control study. For each patient we measured 22 urinary biomarkers and serum Carcinoembryonic antigen (CEA) using either ELISAs or the Randox biochip technology, BAT. We analysed the collated data, using Forward Wald binary logistic regression analyses. Algorithms based on demographic variables were designated as Prior Predicted Probability (PPP). We then created algorithms incorporating PPP as a single variable, together with biomarkers.We determined Areas under the Receiver Operating Characteristic (AUROC) for differentially expressed single biomarkers and multivariate algorithms. AUROC for CEA, Bladder Tumour Antigen (BTA) and Nuclear matrix protein (NMP22) = 0.74; 0.74; and 0.79, respectively. Vascular endothelial growth factor, dDimer, Fas, hyaluronidase, interleukin(IL) IL-1α, IL-6 and IL-8 were also differentially expressed (T-test; p < 0.05). PPP included age and smoking years. In combination, PPP, NMP22 and Epidermal Growth Factor (EGF) achieved AUROC = 0.90, significantly improving upon the AUROC for PPP which was 0.76. Although neutrophil-associated gelatinase lipocalin (NGAL) levels were similar in urines from UC and control patients, a multivariate classifier which comprised age, serum CEA and urinary NGAL and interleukin 8 achieved a respectable AUROC = 0.844. Biomarkers significantly improved upon the AUROC statistic based on demographics. Despite non differential urinary levels across UC and controls, NGAL made a significant contribution to a diagnostic classifier exemplifying the unpredictable nature of the complexities involved in collectives of biomarkers. The impact of biomarkers in multivariate algorithms for bladder cancer diagnosis in patients with hematuria. Abogunrin F, O'Kane HF, Ruddock MW, Stevenson M, Reid CN, O'Sullivan JM, Anderson NH, O'Rourke D, Duggan B, Lamont JV, Boyd RE, Hamilton P, Nambirajan T, Williamson KE. Cancer. May 15;118(10) [2012] American Cancer Society Inc Citation Format: Michael Stevenson, Cherith Reid, Brian Duggan, Mark Ruddock, Kate E. Williamson. Bladder cancer diagnostic algorithms in hematuria populations. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5136. doi:10.1158/1538-7445.AM2013-5136

Reply to the impact of biomarkers in multivariate algorithms for bladder cancer diagnosis in patients with hematuria

Reply to the impact of biomarkers in multivariate algorithms for bladder cancer diagnosis in patients with hematuria

The impact of biomarkers in multivariate algorithms for bladder cancer diagnosis in patients with hematuria

The impact of biomarkers in multivariate algorithms for bladder cancer diagnosis in patients with hematuria

74 OCCUPATIONAL RISK FOR INITIAL BLADDER CANCER DIAGNOSIS IN BRAZIL

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Evidence-based Medicine & Outcomes II1 Apr 201274 OCCUPATIONAL RISK FOR INITIAL BLADDER CANCER DIAGNOSIS IN BRAZIL Sanarelly Adonias, Daher C. Chade, Alexandre C. Sant'Anna, Sabrina T. Reis, Daniel K. Abe, Flavio G.M. Areas, T.T. Suzaki, Katia R. Leite, Miguel Srougi, and Marcos F. Dall'Oglio Sanarelly AdoniasSanarelly Adonias Sao Paulo, Brazil More articles by this author , Daher C. ChadeDaher C. Chade Sao Paulo, Brazil More articles by this author , Alexandre C. Sant'AnnaAlexandre C. Sant'Anna Sao Paulo, Brazil More articles by this author , Sabrina T. ReisSabrina T. Reis Sao Paulo, Brazil More articles by this author , Daniel K. AbeDaniel K. Abe Sao Paulo, Brazil More articles by this author , Flavio G.M. AreasFlavio G.M. Areas Sao Paulo, Brazil More articles by this author , T.T. SuzakiT.T. Suzaki Sao Paulo, Brazil More articles by this author , Katia R. LeiteKatia R. Leite Sao Paulo, Brazil More articles by this author , Miguel SrougiMiguel Srougi Sao Paulo, Brazil More articles by this author , and Marcos F. Dall'OglioMarcos F. Dall'Oglio Sao Paulo, Brazil More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.120AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Although bladder cancer risk factors are well known, it is not clear what is the actual impact of daily occupation on current series. Smoking represents the main preventable risk variable, with almost 45% of cases associated. Occupational hazards is estimated to be related to bladder cancer development in 5% to 25% of patients, with wide variation of findings among different studies. We sought to analyze the impact of occupational risk, comparing patients with bladder cancer according to their professional activitiy and its association to symptoms, stage and oncologic outcomes. METHODS We included 100 patients with bladder cancer after transurethral resection between 2008 and 2011. 64% were male. We analyzed presenting symptoms, stage, grade, and number of lesions. A questionnaire regarding current and past profession, years of work and daily habits were applied in all patients. Patients included in group 1 were those with no professions previously related to bladder cancer risk. Group 2 represented patients at risk due to professions or activities that exposes workers to chemicals known as bladder carcinogens, such as in rubber and chemical industries. Statistical analysis was performed using chi-square and Fisher tests with SPSS v13. RESULTS Patients in group 2 presented significantly higher incidence of disuria as a presenting symptom (p=0.001). Patients in group 2 had a higher incidence of T1 disease at diagnosis (36% vs 18%), although not statistically significant (p=0.059). There was no difference among other variables between groups 1 and 2, such as rate of recurrence (21% vs 22%), 3 or more lesions (22% vs 19%), or grade. Also, other presenting symptoms (hematuria, urinary retention, frequency and urgency) had similar rates between the two groups. CONCLUSIONS Irritative urinary symptoms are more frequently encountered among patients with bladder cancer who are exposed to bladder carcinogens due to professional activities than with no occupational risks. Therefore, presenting symptoms may help in the initial bladder cancer diagnosis in patients with a history of occupational exposure. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e31-e32 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sanarelly Adonias Sao Paulo, Brazil More articles by this author Daher C. Chade Sao Paulo, Brazil More articles by this author Alexandre C. Sant'Anna Sao Paulo, Brazil More articles by this author Sabrina T. Reis Sao Paulo, Brazil More articles by this author Daniel K. Abe Sao Paulo, Brazil More articles by this author Flavio G.M. Areas Sao Paulo, Brazil More articles by this author T.T. Suzaki Sao Paulo, Brazil More articles by this author Katia R. Leite Sao Paulo, Brazil More articles by this author Miguel Srougi Sao Paulo, Brazil More articles by this author Marcos F. Dall'Oglio Sao Paulo, Brazil More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The impact of biomarkers in multivariate algorithms for bladder cancer diagnosis in patients with hematuria

We appraised 23 biomarkers previously associated with urothelial cancer in a case-control study. Our aim was to determine whether single biomarkers and/or multivariate algorithms significantly improved on the predictive power of an algorithm based on demographics for prediction of urothelial cancer in patients presenting with hematuria. Twenty-two biomarkers in urine and carcinoembryonic antigen (CEA) in serum were evaluated using enzyme-linked immunosorbent assays (ELISAs) and biochip array technology in 2 patient cohorts: 80 patients with urothelial cancer, and 77 controls with confounding pathologies. We used Forward Wald binary logistic regression analyses to create algorithms based on demographic variables designated prior predicted probability (PPP) and multivariate algorithms, which included PPP as a single variable. Areas under the curve (AUC) were determined after receiver-operator characteristic (ROC) analysis for single biomarkers and algorithms. After univariate analysis, 9 biomarkers were differentially expressed (t test; P < .05). CEA AUC 0.74; bladder tumor antigen (BTA) AUC 0.74; and nuclear matrix protein (NMP22) 0.79. PPP included age and smoking years; AUC 0.76. An algorithm including PPP, NMP22, and epidermal growth factor (EGF) significantly improved AUC to 0.90 when compared with PPP. The algorithm including PPP, BTA, CEA, and thrombomodulin (TM) increased AUC to 0.86. Sensitivities = 91%, 91%; and specificities = 80%, 71%, respectively, for the algorithms. Addition of biomarkers representing diverse carcinogenic pathways can significantly impact on the ROC statistic based on demographics. Benign prostate hyperplasia was a significant confounding pathology and identification of nonmuscle invasive urothelial cancer remains a challenge.

The impact of biomarkers in multivariate algorithms for bladder cancer diagnosis in patients with hematuria

The impact of biomarkers in multivariate algorithms for bladder cancer diagnosis in patients with hematuria