A Combined Analysis of European Organization for Research and Treatment of Cancer, and Medical Research Council Randomized Clinical Trials for the Prophylactic Treatment of Stage TaT1 Bladder Cancer

Abstract

PURPOSE: The use of prophylactic agents after primary resection can decrease the incidence of tumor recurrence in patients with stage TaT1 bladder cancer. However, the long-term impact on progression to muscle invasive disease as well as on duration of survival is unknown. A combined analysis of individual patient data from previously performed European Organization for Research and Treatment of Cancer (EORTC) and Medical Research Council (MRC) randomized clinical trials was done in an attempt to answer these crucial questions. We compared immediate versus no adjuvant prophylactic treatment after transurethral resection with respect to disease-free interval, time to progression to muscle invasive disease, time to appearance of distant metastases, duration of survival and progression-free survival. MATERIALS AND METHODS: All EORTC and MRC prophylactic, randomized phase III trials with primary or recurrent, stage TaT1 transitional cell bladder cancer that compared transurethral resection alone or with adjuvant prophylactic treatment were included in the study. Four EORTC and 2 MRC trials using intravesical chemotherapy or oral agents and including a total of 2,535 patients were studied. RESULTS: A statistically significant effect of adjuvant treatment over no adjuvant treatment was found in terms of the duration of the disease-free interval (p < 0.01). No clear advantage of adjuvant treatment was shown with respect to progression to invasive disease, time to appearance of distant metastases or duration of survival and progression-free survival. Median survival followup was 7.8 years. CONCLUSIONS: Despite prologation of the disease-free-interval adjuvant treatment has no apparent long-term impact on the evolution of stage TaTi bladder cancer.