Diagnostic and prognostic role of BTA, NMP22, survivin and cytology in urothelial carcinoma

Background: Cytology is a recommended noninvasive urine test for the detection and surveillance of bladder cancer and upper-tract urothelial carcinoma. It is however characterized by poor sensitivity in low-grade tumors. This study aims to determine the diagnostic and prognostic role of BTA, BTA-stat, NMP22, and Survivin. Methods: Urine samples were collected from a total of 105 patients (bladder cancer (n=61), upper-tract urothelial carcinoma (n=44), and controls (n=52). The samples were directly assessed using cytology, BTA-stat (Qualitative test), BTA (chemiluminescence test), NMP22 (Qualitative test), and Survivin (enzyme-linked immunosorbent assay). Cancer progression and recurrence were assessed after a median follow-up of 32 months (4-47 months). Univariate and multivariate analyses were performed using Kaplan-Meier survival analysis and Cox proportional hazards regression. Results: The triple combination of Survivin + BTA + Cytology was the most promising model for discriminating bladder cancer or upper-tract urothelial carcinoma from controls (UTUC group: The area under the curve value 0.97, sensitivity 86%, specificity 96%; BC group: The area under the curve value 0.86 sensitivity 67%, specificity 96%). Univariate survival analysis, showed Cytology (P=0.02; HR=5.35) and Survivin (HR=3.24; P=0.03) to have a significant association with the progression-free survival, while Survivin (HR=4.15; P=0.04) was statistically associated with cancer-specific survival in the bladder cancer group. The multivariable analysis did not show any of these markers as independent prognostic factors. Conclusions: These biomarkers showed a higher sensitivity than cytology, but a poorer specificity. All biomarkers exhibited good diagnostic performance in both bladder cancer and upper-tract urothelial carcinoma. Combining Survivin + BTA + Cytology was superior to the use of a single marker or combining other biomarkers.