Urinary interleukin-8 predicts the response of standard and low dose intravesical bacillus Calmette-Guerin (modified Danish 1331 strain) for superficial bladder cancer.

PURPOSE: We determined whether the proinflammatory cytokine interleukin-8 (IL-8) can serve as a predictor for the response to standard (120 mg.) and low (40 mg.) dose intravesical bacillus Calmette-Guerin (BCG) (modified Danish 1331 strain) for managing superficial bladder cancer in patients at risk for recurrence and progression.

MATERIALS AND

METHODS

We randomized 26 patients with superficial bladder cancer to receive a 6-week course of standard dose 120 mg. or low dose 40 mg. intravesical BCG. Voided urine samples were collected immediately before and after (2 and 4 hours) BCG instillation. Urine samples were centrifuged at 1,500 rpm for 8 minutes and stored at -80C. IL-8 was measured using a commercial enzyme-linked immunosorbent assay. Patients were monitored for recurrence, progression and side effects of BCG treatment at 3-month intervals.

RESULTS

At a median followup of 24 months (range 12 to 30), 5 and 6 patients who received a standard and low dose, respectively had disease recurrence and/or progression (nonresponders). At 4 hours after BCG mean Il-8 levels plus or minus SD were significantly higher in responders than in nonresponders (1,099.33 +/- 708.51 versus 261.82 +/- 182.66 pg./ml., p = 0.001). There was no difference at 4 hours in mean IL-8 levels in the standard and low dose groups (596.92 +/- 546 and 893 +/- 798.67 pg./ml., respectively, p = 0.28). In all patients who remained disease-free IL-8 levels were greater than 400 pg./ml. In 9 of the 11 patients with disease recurrence/progression IL-8 levels were less than 400 pg./ml.

CONCLUSIONS

IL-8 secretion after the initial intravesical BCG instillation strongly correlates with the possibility of future recurrence/progression. The quantitative IL-8 response to low and standard dose intravesical BCG (Danish 1331) is similar.