Intravesical chemotherapy for maximum prophylaxis of new early phase superficial bladder carcinoma treated by transurethral resection: A combined analysis of trials by the Japanese Urological Cancer Research Group using smoothed hazard function

BACKGROUND. The effect of intravesical instillation of doxorubicin or epirubicin after transurethral resection (TUR) was estimated from the data of five randomized clinical trials in Japan. The authors provided the estimated hazard function plots with a smoothing technique, to evaluate the prophylactic effect of an intravesical therapy over time and to estimate the natural history of superficial bladder carcinoma. METHODS. Data on a total of 1732 patients from 5 studies of the Japanese Urological Cancer Research Group who were eligible to receive doxorubicin and epirubicin were analyzed. The patients were divided into four subgroups based on their background characteristics. Their tumors were categorized as 'primary and solitary,' 'primary and multiple,' 'recurrent and solitary,' or 'recurrent and multiple.' RESULTS. Multivariate analysis revealed that intravesical instillation reduced the risk of recurrence to about one-half to two-thirds compared with the controls. The shapes of the graphs that estimated the hazard function for patients with no prophylaxis indicated that multiple tumors showed an earlier peak of recurrence than solitary tumors and recurrent tumors had a higher hazard of recurrence than primary tumors. Graphic presentation of the hazard function in each subgroup suggested that the effect of prophylaxis continued for 500 days after TUR but not for longer. CONCLUSIONS. This analysis indicated that there are two patterns of tumor recurrence of superficial bladder carcinoma after TUR, namely, early phase and late phase. Intravesical chemotherapy may be effective mainly in reducing the hazard for recurrence in the early phase.