Comparative sensitivity of urinary CYFRA 21-1, urinary bladder cancer antigen, tissue polypeptide antigen and NMP22*to detect bladder cancer

Purpose: We compare the individual and combined sensitivity of urinary CYFR A 21-1, urinary bladder cancer antigen, tissue polypeptide antigen and NMP2 2 to detect bladder cancer, evaluate the false-positive rates for different pathological conditions, and assess differential sensitivity regarding his tological and clinical characteristics of disease. Materials and Methods: A total of 267 subjects entered the study. Sensitivi ties of the tests were evaluated in 111 patients with active bladder cancer and 76 with no evidence of disease. False-positive rates were evaluated in 80 symptomatic and asymptomatic controls, including patients with benign u rological conditions and nonbladder malignancies, and healthy subjects. CYF RA 21-1 was determined by electrochemoluminescent immunoassay in the Elecsy s 2010,* urinary bladder cancer antigen was quantified by enzyme linked imm unosorbent assay (IDL Biotech)dagger, tissue polypeptide antigen was measur ed by the Prolifigen TPA-IRMA double dagger and NMP22 was assayed by enzyme linked immunosorbent assay (Matritech). Cutoffs were obtained by the 95% p ercentile in patients with no evidence of disease, which gave a 95% specifi city for all biomarkers. Differences in sensitivity of urinary biomarkers r egarding stage, grade, tumor size, pattern of growth, focality and recurren ce were evaluated. Results: At a specificity of 95% cutoffs were 5.4 ng./ml. for CYFRA 21-1, 1 5.5 mu g./l. for urinary bladder cancer antigen, 760.8 U./1. for tissue pol ypeptide antigen and 14.6 U./ml. for NMP22. Using these cutoffs sensitiviti es were 75.7% for NMP22, 83.8% for CYFRA 21-1, 73.9% for urinary bladder ca ncer antigen quantitative and 80.2% for tissue polypeptide antigen. The add itional determination of cytokeratins increased the sensitivity of NMP22. C ytokeratins did not appear to be specific for bladder cancer, and false-pos itives rates were between 20% for urinary bladder cancer antigen and 36% fo r tissue polypeptide antigen for benign urological conditions, and between 40% and 52%, respectively, for nonbladder malignancies. NMP22 showed lower false-positives rates, mainly for benign diseases. Urinary tumor markers ap peared to be associated with some of the most relevant histological and cli nical parameters of bladder cancer. Conclusions: Our preliminary evaluation showed the tests to be potential no ninvasive adjuncts to help determine the need for cystoscopy. The combinati on of 2 tumor markers, NMP22 and 1 cytokeratin (CYFRA 21-1 or urinary bladd er cancer antigen), seemed to be the most effective. Further comparative st udies are needed to assess the promising diagnostic role of these markers.