Nuclear matrix protein-22: a prospective evaluation in a population at risk for bladder cancer. Results from the UroScreen study.

UNLABELLED: What's known on the subject? and What does the study add? The prognosis of bladder cancer significantly depends on tumour stage and time of diagnosis so early diagnosis is desirable to decrease mortality and treatment costs. The NMP22 test is approved for clinical application by the Food and Drug Administration (FDA) of the US. Previous studies have reported values of 47-100% for sensitivity and 58-91% for specificity with this test, but there is no new data on the predictive value of NMP22 for screening bladder cancer (BC). The most important risk factor for BC is the tobacco consumption but occupational exposure to carcinogenic substances, especially aromatic amines, is regarded as another risk factor. The UroScreen study is a prospective longitudinal study for the early detection of BC. To our knowledge, it is the largest prospective validation study conducted over the longest period of time. The study results led us to conclude that, based on the currently available data, NMP22 should not be regarded as an alternative to endoscopy, and we could not make a general recommendation for screening or follow-up. The UroScreen results indicate that urine-based molecular markers could be a suitable addition to urine cytology and the detection of microhaematuria. OBJECTIVE: To evaluate the value of nuclear matrix protein-22 (NMP22) in bladder cancer (BC) screening, and its effect on variables in a prospective study in a high-risk population. PATIENTS AND METHODS: A total of 1772 chemical workers (mean age 62 years) exposed to carcinogenic aromatic amines were enrolled in the study. In all, 7091 screening check-ups in 1609 subjects were performed. Urine samples were collected for a quantitative NMP22 immunoassay, urine analysis and creatinine concentration assessment. Cystoscopy and subsequent transurethral resection were performed where there were suspicious findings. RESULTS: Histopathological analysis found three papillary urothelial neoplasms of low malignant potential, five recurrent BCs and 13 primary BCs. Three tumours were at a muscle-invasive stage (pT2, pT3a or pT3b). We found higher NMP22 concentrations (>10 U/mL) in 224 patients, which correctly predicted BC in six cases (sensitivity 97.29%, specificity 28.57%; negative predictive value 99.04%, positive predictive value 12.24%). Gross haematuria affected NMP22 results (odd ratio [OR] 3.49, 95% confidence interval [CI] 1.81-6.73). Infection also affected NMP22 results (OR 4.13, 95% CI 2.31-7.35). NMP22 was more frequently positive in urine with creatinine concentration >2.5 g/L (OR 1.61, 95% CI 0.91-2.86). CONCLUSIONS: NMP22 outcomes are affected by haematuria, infection and concentrated urine. NMP22 alone cannot be recommended for primary screening in a high-risk population nor as an alternative to cystoscopy during follow-up. A NMP22 test might be a useful adjunct to urine cytology.

Point-of-Care Tests for Bladder Cancer: The Influencing Role of Hematuria.

Introduction. Several point-of-care tests (POCT) are available for the diagnosis of bladder cancer (BC). We evaluate the impact of HU (hematuria) on performance of POCTs. Materials and Methods. Urine from 10 donors was diluted with blood from 0.5 to 0.00625%. BladderCheck(R), BTAstat(R), BCM(R), and BTA(R) tests were applied. Tests were additionally conducted in 54 patients with HU. HU was stratified according to the amount of erythrocytes (RBC)/µL using two systems: (1) no HU; mild microscopic HU; severe microscopic HU; gross HU; (2) I <25 RBCs; <250 II; ≥250 III. Results were compared to HU status and histopathology. Results. Gross HU became evident between 2090 RBCs/µL and 1065/µL. Addition of blood led to default tests in all 4: BladderCheck(R) 0.25%; BCM 0.025%, BioNexia 0.00625%, and BTAstat <0.00625%. Rates of false positives for BladderCheck, BTAstat, BCM, and BioNexia were 5.9, 11.8, 0, and 1.8% without HU and 0, 66.7, 44.4, and 66.7% with HU. BTAstat, BCM, and BioNexia were independently influenced by HU (P < 0.0002). Conclusions. NMP22-BladderCheck was most resistant to blood. The diagnostic yield of all others was significantly influenced by HU. A well-defined HU grading helps to define limits of HU for a reliable interpretation of BC-POCTs.