Preliminary experience in the use of Hyperthermic Intravesical Chemotherapy to treat BCG-Unresponsive high-grade non-muscle invasive bladder cancer.

Objectives:The aim of this study was to evaluate the “HIVEC(Hyperthermic Intra-Vesical Chemotherapy)^TM" treatment in the adjuvant setting of the high-grade non-muscle invasive bladder cancer(NMBC) after BCG(Bacillus Calmette–Guérin) failure.

Materials and Methods:From June 2017 to March 2018, 16 patients with high grade NMIBC (HG-NMIBC) after TURB and with BCG-refractory tumour were enrolled. 6 out of 16 patients(37.5%) were twice BCG failure. Signed informed consent was obtained from all patients. The current standard of care treatment according to guidelines, including radical cystectomy, was also offered. The treatment schedule consisted of six weekly intravesical instillations of HIVEC™ MMC(Mitomycin C) at a concentration of 40 mg MMC diluted in 50 mL of distilled water. The solution was heated to a target temperature of 43 °C and recirculated inside the bladder at 200 mL per min for 60 minutes. Patient tolerance of the procedure was evaluated using the VAS(Visual Analogue Scale) scale.  Mean values with standard deviations (±SD) were computed and reported for all items.

Results:The mean(±SD) age of the patients was 60.93±9.44 years. All patients had an high-risk bladder cancer according to EORTC risk tables. No adverse events were observed during the treatment. The mean(±SD) VAS score was 0.69±1.14. At the first follow-up cystoscopy (five weeks after the last instillation), 3 out of 16 patients (18.75%) experienced a recurrence. Two patients experienced an  HG-NMIBC recurrence and one patient experienced a low-grade NMIBC (LG-NMIBC) recurrence. The others 13 patients were enrolled in a maintenance protocol (three instillations administered monthly). Of these, 6 patients completed the maintenance protocol and were all disease-free. 3 patients completed a second course of maintenance HIVEC™ MMC (six instillations administered monthly) and were all disease-free. Red patches in the bladder were found at the first cystoscopy in 8 out of 16 patients(50%). The biopsy did not revealed CIS (Carcinoma in situ) in all patients.

Conclusions:In our experience, “HIVEC^TM” treatment is safe and effective for patients with NMIBC in the adjuvant settings after BCG failure. The system can be a promising alternative to the radical cystectomy in a well-selected and well-informed group of patients. Some limitations of our study include the small cohort of patients and short follow-up time.