Detection Of Recurrent Bladder Cancer Research Articles

Abstract A072: Oncuria®-Monitor, a non-invasive test for the detection of recurrent bladder cancer: Cross sectional performance evaluation from a multicenter study

Abstract Up to 70% of patients with non-muscle invasive bladder cancer (NMIBC) experience disease recurrence, making it one of the most prevalent cancers in the US. The purpose of this study was to test the performance of Oncuria®-Monitor, a multiplex urinary biomarker assay for the monitoring of voided urine for recurrent bladder cancer. This cross-sectional, multicenter study included a total of 283 subjects with a history of bladder cancer. Voided urine specimens were collected prior to any procedures for multiplex analysis. The diagnostic performance of the biomarker panel was assessed using receiver operator curves (ROC) and descriptive statistical values (e.g., sensitivity and specificity) and compared with the patients’ clinical data and final diagnosis as defined by the results of cystoscopy. Oncuria®-Monitor achieved an overall sensitivity of 94.3%, specificity of 83.6% and negative predictive valuer (NPV) of 96.2% for the detection of recurrent bladder cancer. Patient summary: We conducted a large cross-sectional clinical study for detecting recurrent bladder cancer with a novel, simple urine test (Oncuria®- Monitor), which measures 10 bladder cancer associated proteins in a single voided urine and can be used to detect recurrent bladder cancer. We analyzed urines from 283 patients and demonstrated that Oncuria®-Monitor can detect recurrent bladder cancer with a high degree of accuracy, specifically in patients with high grade or high stage disease. In conclusion, the novel Oncuria®-Monitor urine test can be used to surveil patients with a history of bladder cancer. Citation Format: Zhen Zhang, Florence Le Calvez-Kelm, Makito Miyake, Ian Pagano, Takuto Shimizu, Sergei Tikhonenkov, Sunao Tanaka, Charles J Rosser, Steve Goodison, Hideki Furuya. Oncuria®-Monitor, a non-invasive test for the detection of recurrent bladder cancer: Cross sectional performance evaluation from a multicenter study [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A072.

The Effectiveness of Cytologic Evaluation of Urinary Diversion Specimens and UroVysion Assay as Surveillance Tests in the Detection of Recurrent Bladder Cancer

Introduction: Different surveillance protocols exist for the detection of urothelial carcinoma recurrence in patients that have undergone radical cystectomy (RC) and each protocol varies in choice of test and frequency of testing. Cytologic examination of urinary diversion specimens and UroVysion assay are two surveillance tests that may be used to detect recurrent disease. The cytologic interpretation of urinary diversion specimens is suboptimal since they contain abundant degenerate glandular cells, histiocytes, bacteria, acute inflammation and non-specific debris. In this milieu recurrent disease can be obscured and identification made difficult, if not impossible. The purpose of this study is to evaluate the effectiveness of cytology and UroVysion assay in this subset of patients. Materials and Methods: A Retrospective chart review of 97 patients who underwent RC with cutaneous diversion or orthotopic neobladder reconstructions for bladder cancer andwho also had a LIS (Laboratory Information System) word search result containing “ileal conduit urine” between January 2001 and January 2012was performed. The cytopathology reports for urinary diversion specimens and any UroVysion assays from these patients were reviewed. Cytologic results were divided into positive, suspicious, atypical, negative and unsatisfactory. The atypical category did not imply malignancy or the potential for malignancy, but was used to indicate some degree of variation from cytology seen in traditional urine specimens. Results: A total of 355 urinary diversion cytology reportswere reviewedwith diagnoses as follows: positive e 0, suspicious e 3 (0.8%), atypical e 136 (38.3%), negative e 213 (60%) and unsatisfactory e 3 (0.8%). A total of 56 Urovysion molecular tests were reviewed with interpretations as follows: positive e 3 (5.3%), negative e 39 (69.6%), indeterminate e 2 (3.6%), insufficient e 12 (21.4%). Four of 97 patients (4.1%) had at least one abnormal cytologic result. One cytologic diagnosis of atypical showed no abnormality on pouch biopsy. The remaining 3 patients with abnormal cytologies had no subsequent biopsies at our institution. Two patients had positive Urovysion assays and both these patients had orthotopic neobladder reconstructions. One patient had two subsequent positive Urovysion assay results which are accounted for by the presence of residual transitional cell carcinoma in-situ (TCIS) in the urethra as this patient had a positive urethral margin at the time of his cystoprostatectomy. The second patient with a positive UroVysion assay result occurred in a patient with 5 normal urinary diversion cytologies who was ultimately diagnosed with Stage 4 urothelial cancer (urothelial carcinomametastasis to skin). Thiswas deemed to be a false positive test result based on clinical assessment. None of the four patientswith abnormal cytology results were found to have recurrent disease. Conclusion: The results of this study question the effectiveness of cytologic evaluation of urinary diversion specimens and UroVysion assay as surveillance tests for detecting recurrent bladder cancer.We did not detect any upper tract/urethral recurrence in our series. Furthermore, the UroVysion assay is not FDA-approved for testing urine specimens derived from patients

Urinary Protein Biomarker Panel for the Detection of Recurrent Bladder Cancer

Up to 70% of patients with non-muscle-invasive bladder cancer (NMIBC) experience disease recurrence, making it one of the most prevalent cancers in the United States. The purpose of this study was to test the performance of a multiplex urinary biomarker assay for the monitoring of voided urine for recurrent bladder cancer. This retrospective, multicenter study included a total of 125 subjects with a history of bladder cancer. Voided urine specimens were collected before procedure from these subjects (53 with confirmed tumor recurrence and 72 with confirmed non-tumor recurrence) for analysis. A prediction rule generated from the performance characteristics of 10 single biomarkers (IL8, MMP9, MMP10, SERPINA1, VEGFA, ANG, CA9, APOE, SERPINE1, and SDC1) was measured using ELISA. The diagnostic performance of the biomarker panel was assessed using receiver operator curves (ROC) and descriptive statistical values (e.g., sensitivity and specificity). The combination of all 10 biomarkers outperformed any single biomarker with a calculated AUROC for the diagnostic panel of 0.904 [95% confidence interval (CI), 0.853-0.956]. The multiplex assay achieved an overall sensitivity of 79% and specificity of 88% for recurrent bladder cancer and significantly outperformed the Urovysion cytogenetic assay (sensitivity 42%, specificity 94%) and voided urinary cytology (sensitivity 33%, specificity 90%). A diagnostic panel of 10 urinary biomarkers that accurately detects primary bladder cancer also performs well for the detection of recurrent bladder cancer. The identification of a reliable urine-based surveillance and detection assay would be of benefit to both patients and the healthcare system.

Combinations of Urinary Biomarkers for Surveillance of Patients with Incident Nonmuscle Invasive Bladder Cancer: The European FP7 UROMOL Project

We determined a combination of markers with optimal sensitivity to detect recurrence in voided urine after resection of an incident low grade, nonmuscle invasive bladder tumor. A total of 136 patients with G1/G2 nonmuscle invasive bladder tumor were included in the study at transurethral resection of the incident tumor. At least 3 followup urine samples were required for patient selection. DNA was extracted from the incident tumor and cell pellets of subsequently collected urine samples. We performed FGFR3, PIK3CA and RAS mutation analysis, and microsatellite and methylation analysis on tissue and urine DNA samples. We obtained 716 urine samples. The 136 patients experienced a total of 552 recurrences during a median 3-year followup. Sensitivity for detecting a recurrent tumor varied between 66% and 68% for the molecular tests after patient stratification based on tumor DNA analysis. A combination of markers increased sensitivity but decreased the number of patients eligible for a certain test combination. Combining urine cytology with FGFR3 analysis without stratifying for FGFR3 status of the incident tumor increased sensitivity from 56% to 76%. A combination of markers increased the percentage of patients eligible for urine based followup and the sensitivity of recurrence detection. Adding FGFR3 analysis to urine cytology could be valuable for noninvasive followup of patients with nonmuscle invasive bladder cancer.

Selection of Microsatellite Markers for Bladder Cancer Diagnosis without the Need for Corresponding Blood

Microsatellite markers are used for loss-of-heterozygosity, allelic imbalance and clonality analyses in cancers. Usually, tumor DNA is compared to corresponding normal DNA. However, normal DNA is not always available and can display aberrant allele ratios due to copy number variations in the genome. Moreover, stutter peaks may complicate the analysis. To use microsatellite markers for diagnosis of recurrent bladder cancer, we aimed to select markers without stutter peaks and a constant ratio between alleles, thereby avoiding the need for a control DNA sample. We investigated 49 microsatellite markers with tri- and tetranucleotide repeats in regions commonly lost in bladder cancer. Based on analysis of 50 blood DNAs the 12 best performing markers were selected with few stutter peaks and a constant ratio between peaks heights. Per marker upper and lower cut off values for allele ratios were determined. LOH of the markers was observed in 59/104 tumor DNAs. We then determined the sensitivity of the marker panel for detection of recurrent bladder cancer by assaying 102 urine samples of these patients. Sensitivity was 63% when patients were stratified for LOH in their primary tumors. We demonstrate that up-front selection of microsatellite markers obliterates the need for a corresponding blood sample. For diagnosis of bladder cancer recurrences in urine this significantly reduces costs. Moreover, this approach facilitates retrospective analysis of archival tumor samples for allelic imbalance.

Comparison of ImmunoCyt, UroVysion, and urine cytology in detection of recurrent urothelial carcinoma

ImmunoCyt (uCyt) and UroVysion are ancillary studies that may aid in the detection of urothelial carcinoma in urine specimens. We compared ImmunoCyt and UroVysion to urine cytology in the ability to detect recurrent urothelial carcinoma. Single voided urine samples were obtained from 100 patients who had a previous history of bladder cancer. All patients underwent cystoscopy immediately after urine sample collection. Forty-one cystoscopically suspicious lesions were biopsied. Urine samples were divided and processed blindly and independently in 3 different laboratories for ImmunoCyt, UroVysion, and urine cytology (ThinPrep method). Of the 41 cystoscopically positive cases, most cystoscopy findings showed multiple tumors that were papillary and less than 1 cm. Biopsies showed many low-grade tumors (54%). Overall sensitivity of cytology for low- and high-grade urothelial cell carcinoma was 15% and 27%, whereas ImmunoCyt was 62% and 91% and UroVysion was 8% and 18%, respectively. Overall specificity of cytology was 97%, whereas ImmunoCyt was 63% and UroVysion was 90%. ImmunoCyt is more sensitive than either cytology or UroVysion in detecting low-grade tumors. Both cytology and UroVysion have comparable specificity in cystoscopically negative cases. Whereas ImmunoCyt may improve the cytological detection of recurrent bladder cancer, UroVysion may be used as a confirmatory test for either cytology or ImmunoCyt.

Bladder Cancer Detection Using FISH (UroVysion Assay)

UroVysion is a fluorescence in situ hybridization assay that was developed for the detection of bladder cancer in urine specimens. It consists of fluorescently labeled DNA probes to the pericentromeric regions of chromosomes 3 (red), 7 (green), and 17 (aqua) and to the 9p21 band (gold) location of the P16 tumor suppressor gene. The UroVysion assay works by detecting urinary cells that have chromosomal abnormalities consistent with a diagnosis of bladder cancer. Studies have shown that UroVysion is more sensitive than urine cytology for the detection of all stages and grades of bladder cancer. UroVysion is Food and Drug Administration-approved for the detection of recurrent bladder cancer in voided urine specimens from patients with a history of bladder cancer and for the detection of bladder cancer in voided urine specimens from patients with gross or microscopic hematuria, but no previous history of bladder cancer. Recent studies also suggest that UroVysion may be useful for assessing superficial bladder cancer patients' response to bacillus Calmette-Guerin therapy and in detecting upper tract urothelial carcinoma.

Considerations on the use of diagnostic markers in management of patients with bladder cancer

Although the incidence of bladder cancer lags behind that of other malignancies, it has the highest rate of recurrence among all US malignancies. The propensity to recur and the possibility of disease progression require aggressive surveillance, which has led to bladder cancer being the most expensive malignancy to treat in the United States. Current non-tailored surveillance strategies applied uniformly to all patients with non-muscle invasive bladder cancer may impose excessive diagnostic burden on patients with low-grade disease for the sake of adequately monitoring those with potentially aggressive disease. The recent identification of several bladder cancer tumor markers has led to attempts to determine if these markers can enhance existing surveillance strategies by possibly tailoring surveillance strategies to individual patients. These markers may result in cost savings by properly identifying which patients can safely delay cystoscopy and which patients require more periodic assessment. Furthermore, we may be able to identify those patients with "occult disease" that require more invasive assessments and earlier aggressive treatment. We will review diagnostic considerations in the use of these markers for the detection of recurrent bladder cancer and summarize the benefits and costs of the more promising bladder cancer markers.

Comparison of NMP22 BladderChek Test and Urine Cytology for the Detection of Recurrent Bladder Cancer

To assess the clinical performance of the NMP22 BladderChek test, which is a qualitative test, and to compare it with voided urine cytology for the detection of recurrent bladder cancer. We also evaluated whether cystoscopy can be omitted from the surveillance protocol by combining the two tests. A total of 131 patients with a history of superficial transitional cell carcinoma of the bladder provided urine samples before a cystoscopic examination. Urine samples were assayed for the presence of NMP22 using the NMP22 BladderChek test and cytology was performed by a cytopathologist. Selected patients underwent a biopsy, with appropriate additional therapy. Results of the two tests were compared with that the results of cystoscopy, which was retained as the gold standard. For positive biopsies, the results of the NMP22 test and cytology were also correlated with the tumor stage and grade. Of the 46 recurrences detected by cystoscopy, the NMP22 test was positive in 39 cases and cytology in 19 cases. The sensitivity of the NMP22 test was 85%, which was significantly greater than that of cytology (41%). In particular, for low-risk tumors it was eight times more sensitive than cytology. The specificities of the NMP22 test and cytology were 77 and 96%, respectively. Combining the two tests increased overall sensitivity to 91%. However, 9% of the tumors were still not detected. The NMP22 BladderChek test is an in vitro qualitative test that is easily available and cheap; it can be performed by a urologist in the office and results can be interpreted within 30 min. The NMP22 test is superior to cytology for all grades and stages in the detection of recurrence in patients with a history of superficial bladder cancer. Our study indicates that the NMP22 test can be used as a substitute for urine cytology. The NMP22 test cannot replace cystoscopy, but it can be used as an adjunct to cystoscopy in the surveillance protocol for patients with superficial bladder cancer.

Comparative Evaluation of the Nuclear Matrix Protein, Fibronectin, Urinary Bladder Cancer Antigen and Voided Urine Cytology in the Detection of Bladder Tumors

We evaluate the diagnostic efficacy of nuclear matrix protein-22 (NMP22, Matritech, Newton, Massachusetts), fibronectin and urinary bladder cancer antigen (UBC, IDL Biotech, Borlange, Sweden) compared with voided urine cytology in the detection of bladder cancer. A total of 168 patients provided a single voided urine sample for NMP22, fibronectin an ideal monoclonal for urinary bladder cancer and cytology before cystoscopy. Cystoscopy was done for all patients as the reference standard for identification of bladder cancer. Biopsy of any suspicious lesion was performed for histopathological examination. Of the 168 cases 100 were histologically diagnosed as bladder cancer, whereas the remaining 68 had benign urological disorders. A group of 47 healthy volunteers were also enrolled in this study. Voided urine was evaluated by NMP22, fibronectin and UBC, and their values were expressed relative to mg. creatinine. The optimal threshold values for NMP22, fibronectin and UBC were calculated by receiver operator characteristics curves as 27 units per mg. creatinine, 198 mg./mg. creatinine and 13 ng./mg. creatinine, respectively. The levels and positive rates of the 3 parameters were significantly higher in the malignant group compared to either the benign group or normal controls. Of the entire group NMP22, fibronectin and UBC were positive in 93.2%, 91% and 68.2%, respectively in bladder cancer cases with positive cytology. Moreover, these positive rates were significantly higher in bilharzial bladder cancer cases (58.8%, 67.5%, 58.8%, respectively) compared to nonbilharzial cases (35.6%, 36.3%, 31.1%). Overall sensitivity and specificity were 85% and 91.3% for NMP22, 83% and 82.6% for fibronectin, 67% and 80.8% for UBC and 44% and 100% for voided urine cytology. Combined sensitivity of voided urine cytology with the 3 biomarkers together was higher than either combined sensitivity of voided urine cytology with 1 of the biomarkers or than that of the biomarker alone. Our data indicate that NMP22 and fibronectin had superior sensitivities compared to UBC and voided urine cytology, while NMP22 and voided urine cytology had the highest specificities. The combined use of markers increased the sensitivity of cytology from 44% to 95.3%. The higher sensitivities of markers in bilharzial than nonbilharzial bladder cancer highlight their clinical use in screening patients with urinary bilharziasis.

SENSITIVITY OF HUMAN COMPLEMENT FACTOR H RELATED PROTEIN (BTA STAT) TEST AND VOIDED URINE CYTOLOGY IN THE DIAGNOSIS OF BLADDER CANCER

We compared the sensitivity of the BTA statdagger test, a rapid, noninvasive, qualitative urine test that detects bladder tumor associated antigen (human complement factor H related protein) in urine, to that of voided urine cytology in patients with primary bladder cancer. We also assessed the effect of tumor size, number, histological grade and stage on test sensitivity. We evaluated 151 patients with newly diagnosed bladder cancer in a prospective multicenter study. A voided urine sample obtained before transurethral bladder tumor resection was divided for culture, cytology and BTA stat testing. Overall sensitivity of the BTA stat test and urine cytology for detecting primary bladder cancer was 81.5% and 30.3%, respectively (p <0.0001). The sensitivity of each test increased as tumor size, number, histological grade and stage increased. Sensitivity of the BTA stat test was superior to that of voided urine cytology in all tumor categories. This noninvasive, easy to perform, point of care test may have the potential to replace cytology for diagnosing bladder cancer.

CHROMOSOME 9 MONOSOMY BY FLUORESCENCE IN SITU HYBRIDIZATION OF BLADDER IRRIGATION SPECIMENS IS PREDICTIVE OF TUMOR RECURRENCE

Bladder irrigation specimens are effective for sampling the urothelium for detection of recurrent bladder cancer. These specimens can be evaluated by cytology or quantitative techniques. Proliferation and ploidy changes are readily detected using deoxyribonucleic acid (DNA) cytometry. Tumor associated chromosomal aberrations can be assayed using fluorescence in situ hybridization (FISH). The prognostic values of DNA cytometry, and chromosome 9 and 9p21 FISH on exfoliated cells from bladder irrigation specimens from 61 bladder cancer patients were evaluated. A total of 61 consecutive bladder irrigation specimens were obtained during cystoscopy. DNA cytometry was performed by image analysis. FISH was performed using a centromeric chromosome 9 probe and a cosmid contig (COSp16) probe to the CDKN2A/p16 tumor suppressor region of 9p21. Proportional hazards regression analysis was performed with statistical software to test the predictor variables of initial patient status (presence of tumor), COSp16 fraction (the proportion of COSp16 signals relative to centromeric probe signals), monosomic and hyperdisomic fractions of the chromosome 9 probe, and hyperdiploid fraction from DNA cytometry. Median time to recurrence was calculated using statistical software survival analysis. Initial patient status and monosomy of chromosome 9 were predictive of bladder cancer recurrence (p <0.0001 and p = 0.0073, respectively). The 11 patients with chromosome 9 monosomy fractions greater than 15% and a visible tumor had a median time to recurrence of 105 days. In contrast, only 8 of the 25 patients with chromosome 9 monosomy fractions less than 15% and no visible tumor had recurrence within 560 days. Median time to recurrence was 185 days for 6 patients with chromosome 9 monosomy fractions greater than 15% and no visible tumor, and 225 for 19 with chromosome 9 monosomy fractions less than 15% and a visible tumor. Hyperdiploid fraction was suggestive but not predictive of bladder cancer recurrence (p = 0.078). COSp16 and hyperdisomic fractions were not predictive of bladder tumor recurrence (p = 0.11 and p = 0.30, respectively). Chromosome 9 monosomy by FISH was predictive of bladder tumor recurrence. Furthermore, our findings support the hypothesis that losses of tumor suppressor genes on chromosome 9 are critical, perhaps initiating genetic events in bladder cancer.

NONINVASIVE DETECTION OF BLADDER CANCER WITH THE BTA STAT TEST

We assess the sensitivity and specificity of the noninvasive BTA stat urine test for detection of primary and recurrent bladder cancer with special reference to the size, grade and stage of the tumors, and examine the effect of intravesical bacillus Calmette-Guerin treatment on the results. A total of 250 patients recruited from 3 medical centers provided voided urine samples for the BTA stat test and cytopathological study. Of these patients 162 were monitored following resection of bladder tumors and 88 were evaluated for the first time for hematuria or irritative voiding symptoms. Each patient underwent cystoscopy. Biopsies were obtained when a bladder tumor was seen or if carcinoma in situ was suspected. The sensitivity, specificity and accuracy of the BTA stat test were compared to standard voided urine cytology. No tumor was found in 122 patients, primary transitional cell carcinoma was found in 71 and cystoscopy revealed recurrent tumors in 57. Overall sensitivity of the BTA stat test was 82.8% and specificity was 68.9%. Sensitivity of urine cytology was 39.8% and specificity was 95.1%. The BTA stat test detected 90.1% of the primary and 73.7% of the recurrent tumors. All patients with carcinoma in situ, high grade tumors, muscle invasive cancer and tumors larger than 2 cm. were diagnosed by the BTA stat test. The BTA stat test can be used as a screening test for bladder cancer in patients with hematuria or irritative voiding symptoms and for surveillance of those who have not been treated with intravesical bacillus Calmette-Guerin.

Detection of Bladder Cancer Recurrence by Microsatellite Analysis of Urine

A reliable, noninvasive method for monitoring patients with transitional cell carcinoma (TCC) of the bladder would be of great clinical benefit. Cystoscopy is currently the gold standard, but it is invasive, expensive and uncomfortable for the patient. Recently, we demonstrated a novel approach for the detection of primary bladder cancer based on microsatellite analysis of urine DNA. To determine the feasibility of this technique for following-up patients with TCC, we tested serial urine samples from 21 patients who had been treated for bladder cancer with 20 polymorphic microsatellite markers in a blinded fashion. We detected recurrent lesions in 10 out of 11 patients and correctly predicted the existence of a neoplastic cell population in the urine of two patients, 4 and 6 months before cystoscopic evidence of the tumor. The assay was negative in 10 of 10 patients who had no evident cancer. Microsatellite analysis of urine sediment represents a novel and potentially powerful clinical tool for the detection of recurrent bladder cancer.

Improved Detection of Recurrent Bladder Cancer Using the Bard BTA stat Test

No AccessJournal of UrologyUrological Survey: Abstracts: Principles of Oncology and Immunology, and Tumors of Bladder, Penis and Urethra1 Feb 1998Improved Detection of Recurrent Bladder Cancer Using the Bard BTA stat Test M.F. Sarosdy, M.A. Hudson, W.J. Ellis, M.S. Soloway, R. deVere White, J. Sheinfeld, M.V. Jarowenko, P.F. Schellhammer, E.W. Schervish, J.V. Patel, G.W. Chodak, D.L. Lamm, R.D. Johnson, M. Henderson, G. Adams, B.A. Blumenstein, K.R. Thoelke, R.D. Pfalzgraf, H.A. Murchison, and S.L. Brunelle M.F. SarosdyM.F. Sarosdy More articles by this author , M.A. HudsonM.A. Hudson More articles by this author , W.J. EllisW.J. Ellis More articles by this author , M.S. SolowayM.S. Soloway More articles by this author , R. deVere WhiteR. deVere White More articles by this author , J. SheinfeldJ. Sheinfeld More articles by this author , M.V. JarowenkoM.V. Jarowenko More articles by this author , P.F. SchellhammerP.F. Schellhammer More articles by this author , E.W. SchervishE.W. Schervish More articles by this author , J.V. PatelJ.V. Patel More articles by this author , G.W. ChodakG.W. Chodak More articles by this author , D.L. LammD.L. Lamm More articles by this author , R.D. JohnsonR.D. Johnson More articles by this author , M. HendersonM. Henderson More articles by this author , G. AdamsG. Adams More articles by this author , B.A. BlumensteinB.A. Blumenstein More articles by this author , K.R. ThoelkeK.R. Thoelke More articles by this author , R.D. PfalzgrafR.D. Pfalzgraf More articles by this author , H.A. MurchisonH.A. Murchison More articles by this author , and S.L. BrunelleS.L. Brunelle More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)63878-3AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Improved Detection of Recurrent Bladder Cancer Using the Bard BTA stat Test." The Journal of Urology, 159(2S), pp. 601–602 University of Texas Health Science Center, San Antonio, Texas, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, Bard Diagnostic Sciences, Inc., Redmond, Providence Hospital and Clinics, Everett, Washington, University of Miami, Miami, Florida, University of California, Davis, California, Memorial Sloan Kettering Cancer Center, New York, New York, Hershey Medical Center, Hershey, Pennsylvania, Eastern Virginia Graduate School of Medicine, Norfolk, Virginia, Michigan Institute of Urology, Warren, Michigan, Washington University, Urologic Specialists, St. Louis, Urology Surgical Associates, Springfield, Missouri, University of Chicago, Chicago, Illinois, West Virginia University Health Sciences Center, Morgantown, West Virginia, and Norwood Clinic, Birmingham, Alabama.© 1998 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 159Issue 2SFebruary 1998Page: 601-602 Advertisement Copyright & Permissions© 1998 by American Urological Association, Inc.MetricsAuthor Information M.F. Sarosdy More articles by this author M.A. Hudson More articles by this author W.J. Ellis More articles by this author M.S. Soloway More articles by this author R. deVere White More articles by this author J. Sheinfeld More articles by this author M.V. Jarowenko More articles by this author P.F. Schellhammer More articles by this author E.W. Schervish More articles by this author J.V. Patel More articles by this author G.W. Chodak More articles by this author D.L. Lamm More articles by this author R.D. Johnson More articles by this author M. Henderson More articles by this author G. Adams More articles by this author B.A. Blumenstein More articles by this author K.R. Thoelke More articles by this author R.D. Pfalzgraf More articles by this author H.A. Murchison More articles by this author S.L. Brunelle More articles by this author Expand All Advertisement PDF downloadLoading ...

Improved Detection of Recurrent Bladder Cancer Using the Bard BTA stat Test

Improved Detection of Recurrent Bladder Cancer Using the Bard BTA stat Test

Clinical evaluation of the BTA trak assay and comparison to voided urine cytology and the bard BTA test in patients with recurrent bladder tumors

Objectives To assess the clinical performance of the BTA TRAK assay and to compare it with that of voided urine cytology (VUC) and the Bard BTA test (BTA) in the detection of recurrent bladder cancer (BC). Methods The study was performed on randomly selected archival voided urine samples for many of which VUC and/or BTA information was available. Sensitivity was determined in samples from patients with histologically confirmed recurrent BC. Specificity was determined in samples from healthy volunteers, patients with three categories of current medical conditions, and patients with a history of BC but no current evidence of disease. Results The TRAK assay was positive in 156 of 216 samples for patients diagnosed with BC, for an overall sensitivity of 72%. Mean values increased with progressing grade and stage of disease. In the comparison between TRAK and VUC, the overall sensitivities were 68% and 25%, respectively ( P < 0.001 ). For Stages Ta and T1 and for all tumor grades, the sensitivity of the TRAK assay was significantly greater than that of VUC ( P < 0.001 ). TRAK sensitivity was also significantly better than that of BTA (73% versus 58%, P = 0.005). The specificity of the TRAK assay ranged from 75% in samples from patients with genitourinary disease to 97% in healthy volunteers. Conclusions The TRAK assay is superior to VUC and the original BTA test in the detection of BC. The results of the study indicate that the TRAK assay may be a useful adjunct to cystoscopy in the management of patients with recurrent BC.

Improved detection of recurrent bladder cancer using the bard bta stat test

To evaluate the BTA stat Test in the detection of recurrent bladder cancer. Sensitivity and specificity were determined using frozen voided urine samples from patients with recurrent bladder cancer, volunteers, patients with nonurologic conditions, and patients with a history of bladder cancer but free of disease. Results of cytology and the original BTA Test were compared with the sensitivity of the BTA stat Test in a large subgroup of the patients with cancer. The BTA stat Test detected 147 (67%) of 220 recurrent cancers. For those urine samples with previous cytologic and BTA Test results available, cytology had a sensitivity of 23%, the BTA Test 44%, and the BTA stat Test 58% for detection of recurrent cancer (P < 0.001, stat versus cytology). The specificity of the BTA stat Test was 72% for benign genitourinary disease and 95% in healthy volunteers. The BTA stat Test has high sensitivity and is significantly superior to voided urine cytologic analysis in the detection of recurrent bladder cancer.

Detection of bladder cancer recurrence by microsatellite analysis of urine.

A reliable, noninvasive method for monitoring patients with transitional cell carcinoma (TCC) of the bladder would be of great clinical benefit. Cystoscopy is currently the "gold standard," but it is invasive, expensive and uncomfortable for the patient. Recently, we demonstrated a novel approach for the detection of primary bladder cancer based on microsatellite analysis of urine DNA. To determine the feasibility of this technique for following-up patients with TCC, we tested serial urine samples from 21 patients who had been treated for bladder cancer with 20 polymorphic microsatellite markers in a blinded fashion. We detected recurrent lesions in 10 out of 11 patients and correctly predicted the existence of a neoplastic cell population in the urine of two patients, 4 and 6 months before cystoscopic evidence of the tumor. The assay was negative in 10 of 10 patients who had no evident cancer. Microsatellite analysis of urine sediment represents a novel and potentially powerful clinical tool for the detection of recurrent bladder cancer.

Efficient scheduling of cystoscopies in monitoring for recurrent bladder cancer.

Proper timing for repeated evaluations is difficult to assess. The authors analyzed scheduling of cystoscopy to monitor patients for detection of recurrent bladder cancer assuming that 1) minimizing tumor detection delay helps prevent cancer morbidities; 2) only limited numbers of cystoscopies are available; 3) prediction of recurrence or progression to invasive cancer is uncertain; 4) future tumors recur according to a Poisson process. Assumptions 3 and 4 permit estimation of each patient's recurrence rate. Thus, patients may be compared according to their relative risks of future tumors. With these assumptions, nonlinear optimization theory was used to calculate monitoring schedules for a model practice. Given 5.4 available visits per week per 100 patients, cystoscopy was recommended in 9-11 weeks for high-risk patients and in 30-40 weeks for low-risk patients, depending on stages, grades, and numbers of previous tumors. In contrast, standard cystoscopy was recommended in 13, 26, or 52 weeks, depending only on time elapsed since last recurrence. The calculated schedule implied an average detection delay for potentially invasive tumors of eight weeks, while standard practice led to detection delays of 11 weeks (38% worse). These results suggest that inclusion of each patient's tumor history in an optimization approach may improve follow-up care for patients who have superficial bladder cancers. This approach is being evaluated in a larger clinical setting.