title: 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: OBJECTIVE
  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.
  
  
  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 collected before cystoscopy. All patients underwent transurethral resection of bladder lesions or mapping. and were followed for a mean (range) of 27.3 (3-65) months.
  
  
  RESULTS
  In the 406 patients with bladder cancer, the overall sensitivity was 85% for NMP22, 70% for BTAstat and 62% for VUC. For histological grades 1-3 the sensitivity in detecting transitional cell carcinoma was 82%, 89% and 94% for NMP22, 53%, 76% and 90% for BTAstat, and 38%, 68% and 90% for VUC, respectively. Although the sensitivity in detecting invasive carcinoma was >85% for all the tests. NMP22 and BTAstat were statistically more sensitive than VUC for superficial tumours. The optimal threshold value for NMP22, calculated using the receiver operating characteristics curve was 8.25 U/mL. The specificity was 68% for NMP22, 67% for BTAstat, and 96% for VUC. The specificity of VUC remained >87% and was independent of benign histological findings. In contrast, in patients with no apparent genitourinary disease on histology, NMP22 and BTAstat had significantly higher specificity (94% and 92%, respectively: P=0.003) than in the group with chronic cystitis (52% for both tests). Forty patients having no bladder cancer at biopsy had a recurrence after a mean (range) follow-up of 7.7 (3-15) months: all had a previous history of bladder cancer. According to subsequent recurrence, the prognostic positive and negative predictive values were 18% and 91% for NMP22, 13% and 88% for BTAstat, and 79% and 91% for VUC. Both false-positive VUC and NMP22 tests predicted recurrence (log-rank test, P<0.001 and P=0.004, respectively), but the BTAstat test produced no similar correlation (P=0.778).
  
  
  CONCLUSIONS
  The NMP22 and BTAstat tests are better than VUC for detecting superficial and low-grade bladder cancer but they have significantly lower specificity. After excluding diseases with the potential to interfere in these tests the overall specificity of both tests is increased considerably. False-positive results from NMP22 and VUC but not from BTAstat in patients followed up for bladder cancer correlate with future recurrences.
authors.affiliation: Department of Urology and Paediatric Urology, Hospital Nordwest, Academic Hospital of Johann-Wolfgang-Goethe-University Frankfurt, Frankfurt/Main, Germany. poulakis@em.uni-frankfurt.de
authors.forename: V
authors.initials: V
authors.lastname: Poulakis
authors.forename: U
authors.initials: U
authors.lastname: Witzsch
authors.forename: R
authors.initials: R
authors.lastname: De Vries
authors.forename: H M
authors.initials: HM
authors.lastname: Altmannsberger
authors.forename: M J
authors.initials: MJ
authors.lastname: Manyak
authors.forename: E
authors.initials: E
authors.lastname: Becht
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000652:urine*; D014408:Biomarkers, Tumor; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000652:urine; D018572:Disease-Free Survival; D005189:False Positive Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007118:Immunoassay / Q000379:methods / Q000592:standards; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000652:urine; D009687:Nuclear Proteins / Q000652:urine*; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000652:urine; D014556:Urine / Q000166:cytology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C112999:bladder tumor-associated antigen; C100379:nuclear matrix protein 22