Preoperative plasma levels of interleukin-6 and its soluble receptor predict disease recurrence and survival of patients with bladder cancer

Purpose: Elevated levels of interleukin-6 (IL-6) are associated with metastasis and poor prognosis in various malignancies. Since the IL-6 soluble receptor (IL-6sR) potentiates the systemic effects of IL-6, each may independently impact the disease process. We tested the hypothesis that preoperative plasma IL-6 and IL-6sR levels would predict cancer stage and prognosis in patients with transitional cell carcinoma of the bladder. Materials and Methods: The study group consisted of 51 patients who underwent radical cystectomy for transitional cell carcinoma and 44 men without cancer. Preoperative plasma levels of IL-6 and IL6sR were measured by enzyme-linked immunosorbent assay and correlated with pathological features and clinical outcome. Results: IL-6 levels were higher in patients with bladder cancer than in healthy controls (p < 0.001). In bladder cancer cases elevated levels of IL-6 and IL-6sR were associated with adverse pathological features, including muscle invasion, lymphovascular invasion and lymph node metastases (p < 0.05). High levels of IL-6sR were also associated with pathological tumor grade (p = 0.036). In separate multivariate models that included clinical stage and grade IL-6 and IL-6sR levels were independent predictors of lymphovascular invasion, metastases to lymph nodes, disease recurrence and disease specific survival (p < 0.05). In a preoperative Cox proportional hazards model IL-6 (p = 0.050) and IL-6sR (p = 0.035) predicted disease specific survival. Conclusions: We found that plasma IL-6 levels were higher in patients with bladder cancer than in healthy controls. Levels of IL-6 and IL-6sR were associated with cancer stage and metastases, and were strong independent predictors of disease recurrence and disease specific survival.