Prognostic Role of Serum IL-6 Levels in Bladder Cancer Patients and Hints of its Origin

Interleukin-6 (IL-6) is associated with adverse clinical outcome in cancer patients. In bladder cancer (BC) patients, higher IL-6 serum levels have been linked with adverse pathologic features, worse overall survival (OS) and cancer-specific survival (CSS). IL-6 is being investigated as a therapeutic target. However, concentrations in tumor-tissue are not investigated in detail. Objective of this study is to analyze the prognostic value of IL-6 in BC patients and to investigate its concentration in tumor tissue.

In this single center prospective observational study, preoperative serum samples of 179 BC patients undergoing radical cystectomy were collected between September 2019 and September 2022. Tumor-tissue of additional 20 patients was collected during transurethral resection or radical cystectomy for investigation of IL-6 in tumor tissue supernatant. IL-6 concentration was measured by ELISA.

Median serum IL-6 concentration was 5.4 pg/mL. High serum IL-6 was an independent predictor of OS (HR 1.95; 95% CI, 1.07-3.55; P = .03) and CSS (HR 2.31; 95% CI, 1.14-4.68; P = .02) in multivariate Cox regression analyses. Patients with advanced tumor stage, lymph node metastasis, and larger tumor size had significantly higher preoperative serum IL-6 concentration (all P < .01). In tumor tissue supernatant, IL-6 concentration was higher in muscle-invasive BC, with a median of 715.4 pg/mL, as opposed to 20.7 pg/mL in pTa tumor stage (P < .01).

Serum IL-6 is a strong predictor of poor survival rates and adverse pathologic features in BC patients. IL-6 concentrations in tumor tissue supernatant correlate with tumor stage. The role of IL-6 in theranostics of bladder cancer deserves more attention.