A comparison of urinary nuclear matrix protein‐22 and bladder tumour antigen tests with voided urinary cytology in detecting and following bladder cancer:the prognostic value of false‐positive results
Abstract:Objectives To evaluate the diagnostic and prognostic value of the nuclear matrix protein-22 (NMP22) and bladder tumour antigen (BTAstat) tests compared with voided urinary cytology (VUC) in detecting and following bladder cancer, assessing particularly the prognostic value of false-positive test results in patients followed up for bladder cancer. Patients and methods From 739 patients suspected of having bladder cancer, voided urine samples for the NMP22 and BTAstat tests, and for VUC and urine analysis, were … Show more
“…Regarding the published data over the last years, it becomes obvious that cytology, but also all other urine bound marker systems, were tested in order to replace cystoscopy for bladder cancer detection. As far as urinary cytology is concerned, this diagnostic indication has to be re-evaluated [7][8][9].…”
Introduction: Cystoscopy and cytology are standard procedures for diagnosis and follow-up of patients with bladder cancer. Urinary cytodiagnosis is a descriptive method for tumor characterization. We correlated histopathologic diagnosis of noninvasive urothelial carcinomas with cytological evaluation and, furthermore, we validated cytology by cytometric analysis. Patients and Methods: 94 patients with a history of bladder cancer were included in the study. 25 patients were negative for tumors, 22 showed pTa G1 carcinomas, 25 had pTaG2 and 22 patients had G3 carcinomas. All patients underwent cytological and cytometric evaluation. Nuclear diameter and circumference were measured for 15 representative nuclei per specimen. Statistical evaluation was performed using Graph Pad Software. Results: Cytology showed excellent tumor detection for G2 and G3 carcinomas, with a sensitivity of 100% combined with a specificity of 100%. Using cytometry, we can significantly distinguish between unsuspicious patients and G1 carcinomas on the one hand and high-grade carcinomas on the other. Furthermore, in 6 of 25 patients (24%) with noninvasive G2 carcinomas, but G3 cytological evaluation, tumor progression occurred. Conclusions: Urinary cytology is an excellent instrument for detection of clinically relevant high-grade bladder cancer. Descriptive alterations of the cytopathology can be validated by objective data using cytometric analysis.
“…Regarding the published data over the last years, it becomes obvious that cytology, but also all other urine bound marker systems, were tested in order to replace cystoscopy for bladder cancer detection. As far as urinary cytology is concerned, this diagnostic indication has to be re-evaluated [7][8][9].…”
Introduction: Cystoscopy and cytology are standard procedures for diagnosis and follow-up of patients with bladder cancer. Urinary cytodiagnosis is a descriptive method for tumor characterization. We correlated histopathologic diagnosis of noninvasive urothelial carcinomas with cytological evaluation and, furthermore, we validated cytology by cytometric analysis. Patients and Methods: 94 patients with a history of bladder cancer were included in the study. 25 patients were negative for tumors, 22 showed pTa G1 carcinomas, 25 had pTaG2 and 22 patients had G3 carcinomas. All patients underwent cytological and cytometric evaluation. Nuclear diameter and circumference were measured for 15 representative nuclei per specimen. Statistical evaluation was performed using Graph Pad Software. Results: Cytology showed excellent tumor detection for G2 and G3 carcinomas, with a sensitivity of 100% combined with a specificity of 100%. Using cytometry, we can significantly distinguish between unsuspicious patients and G1 carcinomas on the one hand and high-grade carcinomas on the other. Furthermore, in 6 of 25 patients (24%) with noninvasive G2 carcinomas, but G3 cytological evaluation, tumor progression occurred. Conclusions: Urinary cytology is an excellent instrument for detection of clinically relevant high-grade bladder cancer. Descriptive alterations of the cytopathology can be validated by objective data using cytometric analysis.
“…Poulakis et al [29] evaluated 739 patients using NMP22 (cutoff ≥8.25 U/ml) and found sensitivities of 79% (165/208), 90% (83/92), and 97% (96/99) in patients with 1, 2-3, and >3 tumors, respectively. On the other hand, Sánchez-Carbayo et al [30] evaluated 187 patients using NMP22 (cutoff ≥14.6 U/ml) and found sensitivities of 72% (18/25) and 75% (61/81) in patients with single and multiple tumors, respectively.…”
Section: Urine-based Markersmentioning
confidence: 99%
“…BTA stat is a qualitative test, while BTA TRAK is quantitative. Both have been performed on fresh, refrigerated, or frozen urine obtained as voided or catheterized specimens [29,31,33,37,43,46,48,49,50,51,52,53,54,55,56,57,58,59,60,61]. …”
Due to the lack of disease-specific symptoms, diagnosis and follow-up of bladder cancer has remained a challenge to the urologic community. Cystoscopy, commonly accepted as a gold standard for the detection of bladder cancer, is invasive and relatively expensive, while urine cytology is of limited value specifically in low-grade disease. Over the last decades, numerous molecular assays for the diagnosis of urothelial cancer have been developed and investigated with regard to their clinical use. However, although all of these assays have been shown to have superior sensitivity as compared to urine cytology, none of them has been included in clinical guidelines. The key reason for this situation is that none of the assays has been included into clinical decision-making so far. We reviewed the current status and performance of modern molecular urine tests following systematic analysis of the value and limitations of commercially available assays. Despite considerable advances in recent years, the authors feel that at this stage the added value of molecular markers for the diagnosis of urothelial tumors has not yet been identified. Current data suggest that some of these markers may have the potential to play a role in screening and surveillance of bladder cancer. Well-designed protocols and prospective, controlled trials will be needed to provide the basis to determine whether integration of molecular markers into clinical decision-making will be of value in the future.
“…Poulakis et al [39] studied NMP22 ® , BTA stat tests and VUC in a total of 739 patients suspected of having bladder cancer. All patients underwent transurethral resection of bladder lesions or mapping, and were followed for a mean (range) of 27.3 (3-65) months.…”
Transitional cell carcinoma of the bladder is the second most common malignancy of the genitourinary tract. Cystoscopy and urine cytology are the traditional most used techniques for diagnosis and surveillance of superficial bladder cancer. Urine cytology is specific for diagnosis of bladder cancer but sensitivity results not high, particularly in low-grade disease. Voided urine can be easily obtained and therefore additional diagnostic urine tests would be ideal for screening or follow-up of transitional cell carcinoma. A number of studies have focused on the evaluation of urinary markers that hold promise as non-invasive adjuncts to conventional diagnostic or surveillance techniques. In this review we discuss several new urinary markers (test for bladder tumor antigen, NMP22®, fibrin degradation products, telomerase, fluorescence in situ hybridization test, flow cytometry) and their role in detection and follow-up of bladder cancer. Most of these markers have higher sensitivity than urine cytology, but voided urine cytology has the highest specificity.
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