Four bladder tumor markers have a disappointingly low sensitivity for small size and low grade recurrence

We determine the sensitivity and specificity of 3 bladder tumor markers in urine, including NMP22 assay (Matritech, Newton, Massachusetts), BTA stat test (Bion Diagnostic Sciences, Inc., Redmond, Washington) and UBC antigen (IDL Biotech, Sollentuna, Sweden), and bladder wash cytology for new and recurrent bladder cancer. We examine whether tumor size, grade, and stage influence sensitivity and specificity of the markers.

A total of 304 samples in 250 patients were studied. There were 174 patients who had a history of bladder cancer, including 93 with and 81 without recurrent tumor at cystoscopy. The other group of patients consisted of 66 with newly diagnosed bladder tumor and 64 investigated for microscopic hematuria that was found to be idiopathic. BTA stat was assayed according to manufacturer instructions. NMP22 and UBC were measured in urine with an enzyme-linked immunosorbent assay. A cutoff level of 4 for NMP22 and 1 for UBC was chosen to get the same specificity for new tumors as BTA stat (75%)

There was a highly significant difference (p <0.001) in all markers between patients with new bladder tumors and those without. The difference was less pronounced for tumor recurrence for NMP22, UBC and BTA stat (p=0.002, 0.016 and 0.244, respectively). The difference between new and recurrent tumors disappeared when corrected for tumor size, grade and stage. The sensitivity for new tumors was 65%, 75% and 60% for NMP22, BTA stat and UBC, respectively. Cytology had a sensitivity of 41% for new tumors at a specificity of 94%. The specificity for recurrence was 64% for NMP22, 54% BTA stat and 72% UBC. The sensitivity was 45% for NMP22, 55% BTA stat and 40% UBC.

Tumor size, grade and stage have a strong impact on sensitivity, and specificity for all 3 tested tumor markers as well as bladder wash cytology. The tumor markers or any combination of them cannot replace followup cystoscopy, mainly because most recurrences are small. The role of the markers for screening high risk populations and as a complement to followup cystoscopy remains to be evaluated.