Systemic Interleukin-6 Response after Intravesical Instillation of Bacillus Calmette-Guérin and Mitomycin C in Superficial Bladder Cancer.

Abstract

Interleukin-6 (IL-6) is proposed to play a significant role in pathogenesis of urinary bladder cancer (UBC). This role may be influenced by chemotherapy (mitomycin C; MMC) or immunotherapy (Bacillus Calmette-Guérin; BCG). A case-control study was conducted to determine IL-6 levels in serum of newly diagnosed cases (NDC) of superficial UBC, as well as in patients treated with MMC or BCG intravesical instillation. A total sample of 111 patients (36 NDC, 45 MMC and 30 BCG) was included, as well as a control group of 107 healthy controls (HC). IL-6 was detected by enzyme-linked immunosorbent assay. Results revealed that median levels of IL-6 were significantly elevated in NDC group (15.8 pg/mL; P<0.001) compared to MMC and BCG groups (7.5 and 5.3 pg/mL, respectively) or HC (4.4 pg/mL); while, there were no significant differences between the latter three groups (MMC, BCG and HC). Receiver operating characteristic curve analysis revealed that IL-6 is a very good predictor of UBC in NDC group versus HC (area under the curve=0.885; 95% confidence interval=0.828-0.942; P<0.001; cut-off value=10.5 pg/mL; Youden index=0.62; sensitivity=80.6%; specificity=81.3%). Logistic regression analysis confirmed this significance and IL-6 was associated with a higher risk of UBC (odds ratio=1.18; 95% confidence interval=1.11-1.26; P<0.001). In conclusion, this study indicated that IL-6 level was upregulated in serum of NDC of UBC. Further, IL-6 level was restored to normal levels after intravesical instillation of MMC or BCG.