Performance of Urine Test in Patients Monitored for Recurrence of Bladder Cancer: A Multicenter Study in the United States (original) (raw)
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Anticipatory Positive Urine Tests for Bladder Cancer
Annals of surgical oncology, 2017
The aim of this study was to establish the criteria defining an anticipatory positive test for bladder cancer. We reviewed all patients at our institution who underwent urine cytology or UroVysion fluorescence in situ hybridization (FISH) and cystoscopy from 2003 to 2012. Test performance and cancer anticipation was assessed using generalized linear mixed models, mixed-effects proportional hazards models, and cumulative incidence curves using tests performed within 30 days of each other as well as within a lag time of 1 year. Overall, 6729 urine tests (4729 cytology and 2040 UroVysion FISH) were paired with gold-standard cystoscopies. Sensitivity and specificity were 63 and 41% for cytology, and 37 and 84% for UroVysion FISH, respectively. A 1-year lag time allowed for cancer anticipation and neither test improved. Among patients with positive cytology and initially negative cystoscopy, the hazard ratio of developing a bladder tumor at 1 year was 1.83; 76% of these patients develope...
Cytology and Urinary Markers for the Diagnosis of Bladder Cancer
European Urology Supplements, 2009
Primary detection and follow-up of patients with non-muscle-invasive (NMI) bladder cancer (BC) is done by urethro-cystoscopy (UCS) and, in most cases, cytology. Many urine-based tests have been developed, and in general, these tests have a higher sensitivity than cytology but a lower specificity. In this review, we assessed the value of urine tests for screening, primary detection, and surveillance of NMIBC. Considering the frequency of UCS for follow-up, having markers for recurrent BC would be especially useful. Therefore, we updated our systematic review to include five commonly studied urine markers (BTA stat, NMP22, uCyt + / Immunocyt, FISH UroVysion, and microsatellite analysis) and cytology for surveillance. The sensitivity and/or specificity of cytology and these five markers were more than 5% lower for patients under surveillance compared to the numbers reported in other reviews, confirming that the performance of urine markers and cytology is lower for the detection of recurrent BC than is UCS. Recent data from the first randomized trial to investigate the possibility of lowering UCS frequency with urinary microsatellite analysis showed substantial underestimation of sensitivity and specificity if the urologist was not aware of the urine test outcome. These results question but do not replace UCS as the gold standard for NMIBC surveillance. In conclusion, cytology is still important as an adjunct for the evaluation of patients with hematuria and the surveillance of patients with high-risk NMIBC. Urine markers other than cytology may play a role in future screening studies and the follow-up of patients with low-grade (G1-2) NMIBC.
Urologic Oncology: Seminars and Original Investigations, 2014
Objective: Several commercial point-of-care (POC) tests are available for urine-based detection of bladder cancer (BC). However, these tests are restricted to dichotomized results (positive or negative), which limits their diagnostic value. Quantitative protein-based tests offer improved risk stratification but require complex methods restricted to specialized centers. Recently, the first quantitative POC system based on the detection of cytokeratin fragments became available. The aim of the study was to evaluate the diagnostic accuracy of this quantitative POC test. Patients and methods: A total of 198 patients having symptoms suspicious for BC were included. All patients received urethrocystoscopy and upper-tract imaging. Urine samples were analyzed by the urine BC antigen (UBC) rapid POC system and evaluated both visually and quantitatively using the concile Omega 100 POC reader. For visual evaluation, different thresholds of band intensity for considering a test positive were applied. Moreover, the UBC enzyme-linked immunosorbent assay (ELISA), urine cytology, and the nuclear matrix protein 22 BladderChek were performed. Sensitivities and specifities were calculated by contingency analyses. Optimal cutoffs of quantitative tests were determined by receiver operating characteristic curves. Results: A total of 61 patients (30.8%) were diagnosed with BC. Visual evaluation of the UBC revealed sensitivities of 38.1% to 71.4% with corresponding specificities of 54.1% to 89.1%, dependent on the threshold of band intensity applied. The quantitative UBC rapid showed a sensitivity of 60.7% and a specificity of 70.1% at optimal cutoff (area under the curve ¼ 0.68). A constant increase of both the probability of BC and high-risk BC with increasing UBC rapid values was observed. UBC concentrations determined by the reader significantly correlated with the UBC ELISA (P o 0.001). The UBC ELISA, the nuclear matrix protein22 BladderChek and cytology showed sensitivities of 48.3%, 16.4%, and 51.7% with specificities of 71.3%, 95.3%, and 78.1%, respectively. Conclusion: The UBC rapid in combination with a quantitative POC-reader system for the first time enables quantitative determination of a BC marker under POC conditions. Diagnostic accuracy is at least equivalent to elaborate ELISA-based measurement. The quantitative use of the UBC rapid test facilitates risk prediction compared with conventional nonquantitative dichotomized POC testing.
Urology, 1999
Objectives. To evaluate the diagnostic performance of the new noninvasive urinary bladder cancer (UBC) rapid test in selected urine voided samples for the detection of transitional cell carcinoma (TCC) of the bladder, and to assess the differential sensitivity of the biomarker regarding the most relevant histologic and clinical parameters of bladder cancer. Methods. Two hundred sixty-seven subjects were entered into the study and classified into five groups: 111 patients with active TCC of the bladder (group 1); 76 follow-up patients with TCC free from disease as confirmed by cystoscopy (group 2); 25 patients with other benign urologic diseases (group 3); 25 patients with other malignant pathologic conditions (group 4); and 30 healthy subjects (group 5). The UBC rapid test was measured by an immunochromatographic method that qualitatively detects the presence of fragments of cytokeratins 8 and 18 in the urine. UBC rapid test differences regarding stage, grade, tumor size, pattern of growth, focality, and recurrence were also evaluated. Results. The sensitivity in group 1 was 78.4% and the specificity in group 2 was 97.4%. Positive and negative predictive values in groups 1 and 2 were 97.4% and 79.0%, respectively, with a global accuracy of 86.1%. False-positive rates were 20.0% and 44.0% for groups 3 and 4, respectively. The sensitivities of the UBC rapid test were associated with the histologic and clinical characteristics of bladder cancer, but not enough to reach statistical significance. Conclusions. The UBC rapid test appears to be a promising noninvasive adjunct that might guide the urologist in the decision to perform cytoscopy for the detection of TCC of the bladder. Further studies appear to be merited to assess its potential diagnostic role.
The diagnostic accuracy of urine-based tests for bladder cancer varies greatly by patient
BMC Urology, 2016
Background: Spectrum effects refer to the phenomenon that test performance varies across subgroups of a population. When spectrum effects occur during diagnostic testing for cancer, difficult patient misdiagnoses can occur. Our objective was to evaluate the effect of test indication, age, gender, race, and smoking status on the performance characteristics of two commonly used diagnostic tests for bladder cancer, urine cytology and fluorescence in situ hybridization (FISH). Methods: We assessed all subjects who underwent cystoscopy, cytology, and FISH at our institution from 2003 to 2012. The standard diagnostic test performance metrics were calculated using marginal models to account for clustered/repeated measures within subjects. We calculated test performance for the overall cohort by test indication as well as by key patient variables: age, gender, race, and smoking status. Results: A total of 4023 cystoscopy-cytology pairs and 1696 FISH-cystoscopy pairs were included in the analysis. In both FISH and cytology, increasing age, male gender, and history of smoking were associated with increased sensitivity and decreased specificity. FISH performance was most impacted by age, with an increase in sensitivity from 17 % at age 40 to 49 % at age 80. The same was true of cytology, with an increase in sensitivity from 50 % at age 40 to 67 % at age 80. Sensitivity of FISH was higher for a previous diagnosis of bladder cancer (46 %) than for hematuria (26 %). Test indication had no impact on the performance of cytology and race had no significant impact on the performance of either test. Conclusions: The diagnostic performance of urine cytology and FISH vary significantly according to the patient demographic in which they were tested. Hence, the reporting of spectrum effects in diagnostic tests should become part of standard practice. Patient-related factors must contextualize the clinicians' interpretation of test results and their decision-making.
A SIDE BY SIDE COMPARISON OF CYTOLOGY AND BIOMARKERS FOR BLADDER CANCER DETECTION
The Journal of …, 2004
Purpose: The identification of accurate bladder tumor markers/tests could improve diagnosis, recurrence monitoring and treatment in patients with bladder cancer. In this study we compared the efficacy of the hyaluronic acid (HA)-hyaluronidase (HAase), BTA-Stat (Bard/Bion Diagnostics, Redmond, Washington), Hemastix (Bayer Corp., Elkhart, Indiana) (hematuria detection) and UBC-Rapid (IDL Biotech, Borlä nger, Sweden) tests, and cytology to detect bladder cancer. The HA-HAase test measures urinary HA and HAase levels, BTA-Stat detects complement factor-H and H related protein in urine, the Hemastix hemoglobin dipstick detects hematuria and UBC-Rapid detects cytokeratin 8 and 18 fragments in urine.
The role of urinary cytology for detection of bladder cancer
European Journal of Surgical Oncology (EJSO), 2005
The aim of the present study was to test the value of urinary cytology in the diagnosis of bladder cancer. Materials and methods. One thousand three hundred and eighty voided urine and bladder wash specimens of 495 patients were evaluated by urinary cytology. All patients then underwent transurethral resection of suspicious bladder areas if cystoscopy and/or preceding biopsy were positive. Statistical differences were analysed using the two-sided Fisher's exact test and Cochran's test (p!0.05). Results. In 495 patients including 142 patients with bladder cancer urinary cytology revealed a sensitivity of 38.0% and a specificity of 98.3% with a positive and negative predictive value of 90.6 and 78.6, respectively. Sensitivity increased significantly with malignancy grade (p!0.05). In high grade tumours sensitivity improved from initial 52.2% up to 78.3% after the third sample. In sensitivity and specificity of voided urine and barbotage washing samples no significant difference was detected. Conclusions. Urinary cytology has its place as an additive diagnostic tool to cystoscopy. None of the currently available urinary markers can replace cystoscopy but are helpful for specific diagnostic problems.
Urine Markers for Bladder Cancer Surveillance: A Systematic Review
European Urology, 2005
Introduction: The follow-up of patients with urothelial cell carcinoma (UCC) of the bladder is done by cystoscopy and, in most cases, cytology. The last decade, many urine-based tests for UCC have been developed and tested in different populations. For the urological practice, considering the amount of follow-up cystoscopies, especially urine markers for recurrent disease would be useful. Therefore, we reviewed the literature on these markers for recurrent UCC and compared our findings with recent review-articles. Methods: We performed a PubMed search. In case of primary and recurrent disease, the study was included if the patients under surveillance were reported separately. Patients with no evidence of disease at surveillance cystoscopy were considered to determine specificity. A marker was included if at least 2 studies from 2 different institutions/ authors were available. Results: The literature review yielded 64 articles. We found 18 markers (BTAstat, BTAtrak, NMP22, FDP, ImmunoCyt, Cytometry, Quanticyt, Hb-dipstick, LewisX, FISH, Telomerase, Microsatellite, CYFRA21-1, UBC, Cytokeratin20, BTA, TPS, Cytology) that met our criteria. BTAstat, NMP22, ImmunoCyt and cytology were evaluated in more than 750 patients. Telomerase, Cytokeratin20 and Hb-dipstick were tested in less than 250 patients. The highest median sensitivities were reported for CYFRA21-1 (85%), Cytokeratin20 (85%) and Microsatellite analysis (82%). The highest specificities were reported for Cytology (94%), BTA (92%) and Microsatellite analysis (89%). In comparison with recent reviews, median sensitivity was !5% lower for the surveillance group in 13/18 urine-based tests while specificity remained relatively constant between different patient groups. Conclusions: To our knowledge, this is the first review that assesses sensitivity and specificity of urine markers solely for UCC surveillance. In our view, Microsatellite analysis, ImmunoCyt, NMP22, CYFRA21-1, LewisX and FISH are the most promising markers for surveillance at this time. Nevertheless, clinical evidence is insufficient to warrant the substitution of the cystoscopic follow-up scheme by any of the currently available urine marker tests. Future studies may test some of the most sensitive and specific assays to reduce the cystoscopy frequency. However, our results show that initiators of these studies should anticipate a lower sensitivity than reported in the current literature. #
Cancer, 2001
BACKGROUND. Cross-section studies have shown the diagnostic characteristics of certain urinary tumor markers for the detection of bladder carcinoma. However, the role of serial urinary tumor markers in the monitoring of patients with bladder carcinoma in daily clinical surveillance has not been completely defined yet. METHODS. The study comprised 1185 urine samples belonging to 232 patients with a previous bladder carcinoma: 106 patients under follow-up (Group 1) and 126 bladder carcinoma patients receiving intravesic instillations (Group 2). Patients were monitored with urinary tumor markers during a one-year follow-up period. Urine samples were collected before cystoscopies and in the intercystoscopic periods for patients in Group 1 and before intravesic instillations for patients Group 2. Urinary bladder carcinoma antigen (UBC), CYFRA 21-1 and nuclear matrix proteins (NMP22) were measured by immunoassays. RESULTS. Monitoring of the disease with urinary tumor markers could detect recurrence sooner than scheduled cystoscopies in 27 patients (87%) for UBC, 27 patients (87%) for CYFRA 21-1, and 26 patients (84%) for NMP22 out of 31 Group 1 patients who recurred; and in 16 patients (67%) for UBC, 17 patients (71%) for cytokeratin fragments (CYFRA) 21-1, and 13 patients (54%) for NMP22 out of 24 Group 2 patients who recurred. The most relevant finding was that persistence of negative urinary markers during follow-up was largely indicative of disease free status in 65 of 75 (87%) patients of Group 1 and 31 of 102 (30%) cases of Group 2. Although false positive results were present, they were mainly associated with sporadic urinary tract infections in 10 of 75 (13%) cases of Group 1 and in 36 of 102 (35%) patients of Group 2; and with urine samples collected in the first two months at the beginning of intravesic therapy in 35 of 102 patients (34%) in Group 2. CONCLUSIONS. Monitoring of bladder carcinoma patients with serial urinary tumor markers could anticipate detection of recurrence. Persistent negative results might postpone and reduce the number of cystoscopies. Once the limitations leading to false positive results are controlled by urinalysis and by starting sample collection when basal levels are reached in patients with intravesic therapy, urinary tumor markers might eventually individualize the intervals between cystoscopies in the surveillance of patients with bladder carcinoma.