Exclusion criteria enhance the specificity and positive predictive value of NMP22*and BTA stat

Purpose: The limitation of current urinary tumor markers is the low specifi city and positive predictive value, which clinically manifests as a high fa lse-positive rate. We analyzed the false-positive data of 2 urinary tumor m arkers, NMP22 and the BTA stat tests. We examined the clinical categories o f the false-positive results, established relative exclusion criteria, and recalculated the specificity and positive predictive value after using the exclusion criteria. Materials and Methods: A total of 278 symptomatic patients who presented to a urology clinic were asked to submit a single voided urine sample. Each s ample was divided into 3 aliquots of which 1 was stabilized with the NMP22 test kit stabilizer and assayed for NMP22, 1 was tested for BTA stat and 1 was sent for cytological examination. All patients subsequently underwent o ffice cystoscopy and bladder biopsy if indicated. Results: Of the 278 symptomatic patients 112 presented with microscopic hem aturia, 77 gross hematuria and 89 chronic symptoms of urinary frequency or dysuria. Of 34 cases (12%) of histologically confirmed bladder cancer NMP22 detected 28 (82.4%), BTA stat 23 (67.7%) and cytology only 10 (29.4%). Whe n atypical cytologies were considered positive, cytology then detected 19 c ases (55.9%). Elevated NMP22 values were positive in 28 cases and false-pos itive in 44 for a specificity of 82% and a positive predictive value of 38. 9%. Similarly, BTA stat test was positive in 23 cases and false-positive in 43 for a specificity of 82.4% and a positive predictive value of 34.9%. Wh en atypical cytologies were considered positive, the specificity and positi ve predictive value were 93% and 55.9%. Greater than 80% of the false-posit ive results were clinically categorized as benign inflammatory or infectiou s conditions, renal or bladder calculi, recent history of a foreign body in the urinary tract, bowel interposition segment, another genitourinary canc er or an instrumented urinary sample. A category of "no known pathology" wa s included in analysis as a control. History of ureteral stents or any bowe l interposition segment had a 100% false-positive rate. Exclusion of all 6 clinical categories improved the specificity and positive predictive value of NMP22 (95.6%, 87.5%) and BTA stat (91.5%, 69.7%), and was similar to uri nary cytology. Conclusions: Awareness and exclusion of the categories of false-positive re sults can increase the specificity and enhance the clinical usefulness of N MP22 and BTA stat tests. Similarly, treating an atypical cytology as positi ve can enhance the sensitivity and usefulness of urinary cytology.