Efficacy of one-year maintenance in early adjuvant chemotherapy for intermediate risk non-muscle-invasive bladder cancer. Preliminary results of a randomized cooperative trial.

Introduction and Objective: The clinical value of early intravesical adjuvant chemotherapy after TUR of intermediate risk non-muscle-invasive bladder cancer (NMI TCCB) is well established. On the other hand, the optimal schedule regimen and the role of maintenance are still debated. The aim of the present study was to evaluate the effectiveness of one-year maintenance schedule in patients submitted to TUR plus adjuvant early intravesical chemotherapy. Methods: Between May 2002 and August 2003, 577 patients, were recruited. All patients underwent TUR and early (within 6 hours) intravesical chemotherapy with epirubicin at the dose of 80 mg diluted in 60 ml of saline solution. When histology was available, 95 patients were excluded from the study since they were harbouring T1G3, Tis or single and primary Ta G1-G2 tumors. Four hundred eighty-two patients with intermediate risk NMI TCCB were randomized according 2 different intravesical instillation schedules: Arm A, 5 more weekly instillations; arm B, 5 more weekly instillations followed by monthly instillations for a total of 16 instillations. All patients were submitted 3-monthly for the first 2-years and then 6-monthly to cytology, cystoscopy and biopsy of every suspicious bladder lesion. Results: Out of 482 randomized patients, 396 are evaluable for toxicity and 392 for efficacy. The tumours were multiple in 318 patients (66.0%) and recurrent in 192 (39.8%). No difference emerged between the 2 arms in relation to tumors’ characteristics. The median follow-up time was 22 months (range: 3-56). Eighty-two (20.9%) patients recurred at a median time of 9 months from TUR. Four patients progressed (1%). The recurrence rate was 24.5% (47/192) in arm A and 17.5% (35/200) in arm B (p=0.05). No difference was evident between the two arms for recurrence rate at 3 months (p=0.06). However, an advantage in favour of maintenance emerged in terms of recurrence rate at 6 (p=0.01), 9 (p=0.04) and 12 months (p=0.03) and in terms of recurrence-free interval (p=0.03). No difference for toxicity was evident according to treatment schedule. Conclusions: A preliminary analysis at 2-year mean follow-up, in patients with intermediate risk NMI TCCB treated with early epirubicin intravesical chemotherapy followed by 5 weekly instillation, the risk of tumour recurrence is significantly reduced without enhanced toxicity by one-year maintenance.