Study of urinary leukocyte count as a new prognostic marker for response to treatment and adverse effects associated with intravesical BCG maintenance therapy for prophylaxis of superficial bladder cancer.

The use of Bacillus Calmette-Guerin (BCG) vaccine as immuno-therapy for superficial bladder cancer constitutes a major progress, although it remains limited by the development of adverse effects and problems related to safety. No individual tool is currently available in clinical practice to predict the efficacy or adverse effects of BCG therapy. These problems are accentuated in the case of maintenance therapy according to the protocol of D.L. Lamm. Objectives: To define whether the urinary leukocyte count observed after intravesical BCG instillation could be associated with adverse effects and efficacy of treatment. Material and Methods: A cohort of 72 consecutive patients (518 instillations) was studied prospectively. We defined four classes of adverse effects associated with BCG, according to their type, severity and duration. In combination with this classification, we performed systematic optical urinary leukocyte count on the third day after each instillation (KOVA-Slide 10). Results: A high urinary leukocyte count (cut-off value: 165,000/ml) was correlated with absence of recurrence (p=0.009). The adverse effect classification also demonstrated that urinary leukocyte count was related to the severity and duration of adverse effects (p<0.0001). Median values observed for class I, II and III adverse effects were 40,000 leukocytes/ml, 150,000 leukocytes/ml and 350,000 leukocytes/ml, respectively. No class IV adverse effects were observed. The risk of developing class III adverse effects was increased when the urinary leukocyte count was greater than 86,000 leukocytes per ml. Conclusion: These results suggest a probable relationship between efficacy and safety of BCG, during maintenance therapy. Randomized prospective studies are necessary, to evaluate urinary leukocyte count as a tool for adaptation and optimization of BCG therapy.