OPTIMAL DELIVERY OF PERIOPERATIVE CHEMOTHERAPY - PRELIMINARY-RESULTS OF A RANDOMIZED, PROSPECTIVE, COMPARATIVE TRIAL OF PREOPERATIVE AND POSTOPERATIVE CHEMOTHERAPY FOR INVASIVE BLADDER-CARCINOMA

Purpose: We performed a planned interim analysis of a randomized trial comparing initial to postoperative chemotherapy for bladder cancer. T he purpose of our analysis was to detect early evidence of survival di fferences, tolerance to therapy influenced by the sequence of treatmen t, predictive value of clinical stage and influence of methotrexate, v inblastine, doxorubicin and cisplatin (M-VAC) on bladder resectability . Materials and Methods: A total of 100 consecutive patients was rando mized to receive 2 M-VAC courses before and 3 courses after surgery (g roup 1) or 5 adjuvant M-VAC courses following cystectomy (group 2). Su rvival, clinical response, clinical and pathological stage, and toxici ty were evaluated in this second timed interim analysis. Results: Of a ll patients 70% received at least 4 M-VAC courses. Overall survival at 31.7 months (range 1.8 to 87.7) was similar in groups 1 (60%) and 2 ( 63%), and independent of clinical stage. Preoperative clinical staging accurately identified patients at high risk for recurrence, while 37 of the 48 group 2 patients (77%) were considered at high risk by patho logical staging (P3b, P4a, node-positive and unresectable disease). Co mparison of pathological stage revealed that 14 of the 51 group 1 pati ents (28%) achieved stage PO while only 1 of the 48 group 2 patients ( 2%) had PO disease at surgery (p = 0.00043). Disease was unresectable in 3 group 1 (6%) and 8 group 2 patients (17%, p = 0.09). Tolerance to treatment was not significantly different in the 2 study arms. Conclu sions: No survival advantage was noted between neoadjuvant and adjuvan t M-VAC in our interim analysis. However, results suggest that M-VAC c hemotherapy may be effective in increasing the resectability of locali zed bladder cancer and may contribute to organ preservation. Clinical stage was a reliable predictor of pathological findings at surgery. Fu ture studies can use clinical staging to determine therapy before surg ery for the select stages that we treated. Identification of the subse t likely to achieve complete pathological remission will permit the se lection of patients for organ preservation strategies.