OBJECTIVES: To evaluate the effectiveness of combined local bladder hyperthermia and intravesical chemotherapy for the treatment of patients with high-grade (G3) superficial bladder cancer. METHODS: Patients with G3 bladder tumors (Stage Ta or T1) were treated with combined intravesical chemotherapy with mitomycin-C and local radiofrequency hyperthermia of the bladder wall. The patients were treated with either a prophylactic protocol (40 mg mitomycin-C) after complete transurethral resection of all tumors or with an ablative protocol (80 mg mitomycin-C) when visible tumor was seen on video-cystoscopy or bladder biopsies were positive for carcinoma in situ. RESULTS: Combined chemo-thermotherapy was administered to 52 patients with high-grade superficial bladder cancer (40 patients with Stage T1 tumor, 11 with Ta, and 3 with concomitant or isolated carcinoma in situ). At a median follow-up of 15.2 months (mean 23, range 6 to 90), no stage progression to T2 or disease-related mortality had occurred. The bladder preservation rate was 86.5%. The prophylactic protocol was administered to 24 patients. After a mean follow-up of 35.3 months, 15 patients (62.5%) were recurrence free. The bladder preservation rate was 95.8%. The ablative protocol was administered to 28 patients. Complete ablation of the tumor was accomplished in 21 patients (75%). After a mean follow-up of 20 months, 80.9% of these patients were recurrence free. The bladder preservation rate for the ablative group was 78.6%. CONCLUSIONS: Combined local bladder hyperthermia and intravesical chemotherapy has a beneficial prophylactic effect in patients with G3 superficial bladder cancer. Ablation of high-grade bladder tumors is feasible, achieving a complete response in about three quarters of the patients.