Influence of age on false positive rates of urine-based tumor markers.
BACKGROUND
Several influencing factors on false positive rates (FPRs) of urine-based tumor markers in the detection of urothelial cancer (UC) have been identified. We evaluated age as a possible influencing factor.


METHODS
Urinary cytology (Cyt), UroVysion (FISH), ImmunoCyt (uCyt+) and NMP22 were determined in 1,554 patients suspicious for UC of the bladder before cystoscopy and in case of cancer detection before TURB. Additionally, upper urinary tract imaging was performed. Maker sensitivity, specificity and FPRs were evaluated in the entire cohort and in subgroups divided by age into <50, ≥ 50-70 and ≥ 70 years. Contingency tables and the Cochrane Armitage tests were used for statistical comparisons.


RESULTS
UC was found in 377 and no UC in 1,177 (75 %) patients. A total of 336 patients were diagnosed with UC of the bladder and 41 with UC of the upper urinary tract. Overall sensitivity and specificity for Cyt were 82 and 82 %: for FISH, 73 and 79 % and for uCyt+, 79 and 75 %, respectively. For NMP22, regardless of the exclusion criteria they were 72 and 34 % and after exclusion of urinary tract infection (UTI) or prior to manipulation 46 and 86 %, respectively. Significantly higher FPRs were found with increasing age for Cyt (p = 0.001), a trend to higher FPRs for uCyt+ (p = 0.11) and almost no difference for FISH (p = 0.63). For NMP22, differences became significant after exclusion of patients with UTI or prior manipulation (p = 0.02).


CONCLUSIONS
The results of the present study give evidence that false positive rates of Cyt and NMP22 increase with age indicating that age should be respected for their correct interpretation.
Department of Urology, Eberhard Karls University Tuebingen, Hoppe-Seyler, Str. 3, 72076, Tuebingen, Germany., marcushorstmann@gmx.ch
M
M
Horstmann
T
T
Todenhöfer
J
J
Hennenlotter
S
S
Aufderklamm
J
J
Mischinger
U
U
Kuehs
G
G
Gakis
A
A
Stenzl
C
C
Schwentner
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology / Q000652:urine*; D014408:Biomarkers, Tumor / Q000652:urine*; D003585:Cell Biology; D015331:Cohort Studies; D003951:Diagnostic Errors / Q000706:statistics & numerical data*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000652:urine; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012737:Sex Factors; D012907:Smoking; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000652:urine*
D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C100379:nuclear matrix protein 22