Utility of serial urinary tumor markers to individualize intervals between cystoscopies in the monitoring of patients with bladder carcinoma

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Abstract
BACKGROUND Cross‐section studies have shown the diagnostic characteristics of certain urinary tumor markers for the detection of bladder carcinoma. However, the role of serial urinary tumor markers in the monitoring of patients with bladder carcinoma in daily clinical surveillance has not been completely defined yet. METHODS The study comprised 1185 urine samples belonging to 232 patients with a previous bladder carcinoma: 106 patients under follow‐up (Group 1) and 126 bladder carcinoma patients receiving intravesic instillations (Group 2). Patients were monitored with urinary tumor markers during a one‐year follow‐up period. Urine samples were collected before cystoscopies and in the intercystoscopic periods for patients in Group 1 and before intravesic instillations for patients Group 2. Urinary bladder carcinoma antigen (UBC), CYFRA 21‐1 and nuclear matrix proteins (NMP22) were measured by immunoassays. RESULTS Monitoring of the disease with urinary tumor markers could detect recurrence sooner than scheduled cystoscopies in 27 patients (87%) for UBC, 27 patients (87%) for CYFRA 21‐1, and 26 patients (84%) for NMP22 out of 31 Group 1 patients who recurred; and in 16 patients (67%) for UBC, 17 patients (71%) for cytokeratin fragments (CYFRA) 21‐1, and 13 patients (54%) for NMP22 out of 24 Group 2 patients who recurred. The most relevant finding was that persistence of negative urinary markers during follow‐up was largely indicative of disease free status in 65 of 75 (87%) patients of Group 1 and 31 of 102 (30%) cases of Group 2. Although false positive results were present, they were mainly associated with sporadic urinary tract infections in 10 of 75 (13%) cases of Group 1 and in 36 of 102 (35%) patients of Group 2; and with urine samples collected in the first two months at the beginning of intravesic therapy in 35 of 102 patients (34%) in Group 2. CONCLUSIONS Monitoring of bladder carcinoma patients with serial urinary tumor markers could anticipate detection of recurrence. Persistent negative results might postpone and reduce the number of cystoscopies. Once the limitations leading to false positive results are controlled by urinalysis and by starting sample collection when basal levels are reached in patients with intravesic therapy, urinary tumor markers might eventually individualize the intervals between cystoscopies in the surveillance of patients with bladder carcinoma. Cancer 2001;92:2820–8. © 2001 American Cancer Society.