Evaluation of urine CYFRA 21-1 for the detection of primary and recurrent bladder carcinoma

BACKGROUND The urinary concentration of soluble cytokeratin 19 fragments, measured by the CYFRA 21-1 assay, may be used for the noninvasive, early detection of bladder carcinoma. METHODS This prospective study examined urine samples from 325 patients. The authors included 152 patients who presented with hematuria or irritative voiding symptoms (Group 1), 107 patients who were under surveillance after undergoing transurethral resection of bladder carcinoma (Group 2), 46 patients with urinary tract pathology other than bladder carcinoma (Group 3), and 20 healthy participants (Group 4). The urine concentration of CYFRA 21-1 was measured by an immunoradiometric assay. The patients in Groups 1 and 2 underwent cytoscopy and urine cytopathology. Biopsies were obtained if a tumor was seen on cytoscopy or if there was a suspicion of carcinoma in situ (CIS). RESULTS The optimal cut-off concentration for the detection of primary bladder tumors, 4.9 μg/L, resulted in a sensitivity of 79.3% and a specificity of 88.6%. The optimal threshold for the detection of recurrent bladder tumors (excluding patients who had been treated with intravesical bacillus Calmette–Guerin [BCG]), 4.04 μg/L, resulted in a sensitivity of 76.2% and a specificity of 84.2%. There was no significant advantage for centrifugation of the urine samples or for determination of the creatinine concentration in the urine samples. The CYFRA 21-1 assay of urine samples provided a three-fold greater sensitivity compared with the sensitivity of cytology for detecting Grade 1 transitional cell tumors. CYFRA 21-1 detected 91.9% of Grade 3 tumors, 100% of CIS, and 92.8% of invasive bladder tumors (T2 or higher classification). The CYFRA 21-1 assay detected all tumors that had positive cytology with the exception of only one tumor. Conversely, the assay identified 71% of primary tumors and 65% of recurrent tumors that were missed by cytopathology. Urinary stones, infection, and previous intravesical BCG immunotherapy caused many false positive results. CONCLUSIONS The urinary CYFRA 21-1 assay is a useful test for the noninvasive detection of bladder carcinoma and for surveillance of patients who were not treated previously with BCG. It may be used in combination with urine cytology and bladder ultrasound. Multi-institutional trials are required to compare the accuracy as well as the cost of this combination of tests with cystoscopy. Cancer 2002;94:2914–22. © 2002 American Cancer Society. DOI 10.1002/cncr.10565