Screening and monitoring for bladder cancer: Refining the use of NMP22

Purpose: While detecting bladder cancer, bladder tumor markers demonstrate improved sensitivity compared with urinary cytology but the current limitat ion is the low specificity and positive predictive value, that is high fals e-positive rate. We examined the clinical categories of the false-positive results, established relative exclusion criteria, and recalculated the spec ificity and positive predictive value of this assay with these criteria. Materials and Methods: A total of 608 patients considered at risk for bladd er cancer presented to a urology clinic and submitted a single urine sample . Of the 608 patients 529 (87%) presented with de novo hematuria or chronic voiding symptoms without a diagnosis of bladder cancer. There were 79 (13. 0%) patients being monitored with a known history of bladder cancer. Each u rine sample was examined via cytology, urinalysis, culture and NMP22(divide d by)(divided by) protein assay. All patients underwent office cystoscopy, and transurethral resection and/or biopsy if a bladder tumor was suspected. Results: Of the 608 patients 226 (37.2%) presented with microscopic hematur ia, 143 (23.5%) with gross hematuria and 239 (39.3%) had chronic symptoms o f urinary frequency or dysuria. There were 52 (8.6%) patients who had histo logically confirmed bladder cancer. Of these 52 cancers NMP22 detected 46 ( 88.5%), whereas cytology identified only 16 (30.8%). When atypical cytology was considered positive, cytology detected 32 (61.5%) cases. In the 135 pa tients with increased NMP22 values the 46 identified tumors were accompanie d by 89 false-positive values yielding a specificity of 83.9% and a positiv e predictive value of 34.1%. These false-positive results were divided into 6 clinical categories. Exclusion of these categories improved the specific ity and positive predictive value of NMP22 to 99.2% and 92.0%, respectively , yielding results similar to urinary cytology (99.8% and 94.1%). Conclusions: Awareness and exclusion of the categories of false-positive re sults can increase the specificity and positive predictive value of NMP22, enhancing the clinical use of this urinary tumor marker.