Urinary interleukin-8 and 18 predict the response of superficial bladder cancer to intravesical therapy with bacillus Calmette-Guerin

Purpose: We evaluate the predictive value of urinary cytokine levels of int erleukin (IL) 8 and 18 for response in patients receiving intravesical baci llus Calmette-Guerin (BCG) for prevention of recurrences of superficial bla dder cancer and treatment of carcinoma in situ. Materials and Methods: In 28 patients with superficial bladder cancer treat ed with BCG IL-8 expression in the urine during the first 6 hours after the first BCG instillation was determined. In 17 patients IL-18 levels were al so evaluated during the first 12 hours after BCG instillation. IL-8 and 18 levels were determined by solid phase double ligand enzyme-linked immunosor bent assay. Results: In 12 of the 28 patients assessed for IL-8 expression disease recu rred after a median followup of 66 months. Median IL-8 expression during th e first 6 hours for these patients was 851 ng. (range 232 to 8,497). Median IL-8 expression during the first 6 hours in patients without recurrence wa s 4,200 ng. (range 432 to;12,232). Of 8 patients with a followup of greater than 36 months 7 (88%) had no recurrent disease and IL-8 levels greater th an 4,000 ng. Patients secreting more than 4,000 ng. IL-8 into the urine aft er BCG have a significantly higher chance of remaining disease-free (p < 0. 05), and those with elevated IL-18 expression have a significantly longer d isease-free survival (p < 0.05). After a median followup of 23 months (rang e 7 to 93) 6 of the 17 patients assessed for IL-18 expression had treatment failure. Median IL-18 expression in those patients during the first 12 hou rs was 2,632 pg. (range 860 to 8,298). Median IL-18 expression during the f irst 12 hours in patients without recurrence was 12,258 pg. (range 1,727 to 151,495). Conclusions: In this study we confirmed the value of quantitative IL-8 expr ession in the urine during the first 6 hours after BCG instillation for sup erficial bladder cancer to predict freedom of disease. Furthermore, to our knowledge we report for the first time the potential value of IL-18 express ion in the urine during the first 12 hours after BCG to predict freedom fro m disease. These findings may help improve the treatment of patients with s uperficial bladder cancer, especially by identifying those with a high risk of disease recurrence and progression after BCG therapy.