Intravesical radiofrequency induced hyperthermia enhances mitomycin C accumulation in tumour tissue

Non-muscle invasive bladder cancer (NMIBC) is a highly recurrent disease with potential progression to muscle invasive disease despite the standard bladder instillations with mitomycin C (MMC) or Bacille Calmette-Guérin immunotherapy. Therefore, alternatives such as radiofrequency-induced chemohyperthermia (RF-CHT) with MMC are being investigated. The mechanism explaining the efficacy of RF-CHT is only partly understood. We examined whether RF-CHT results in higher MMC tissue concentrations as compared to cold MMC instillation.

Prior to a planned transurethral resection of bladder tumour (TURBT), patients with stage Ta NMIBC were allocated to either (1) cold MMC instillation or (2) RF-CHT. After MMC instillation, three biopsies were taken of both normal and tumour tissue. Biopsies were snap-frozen and MMC tissue concentrations were analysed using ultra-performance liquid chromatography.

Eleven patients were included of which six received RF-CHT. Ten patients had TaG2-LG/HG papillary tumours at pathology. One patient in the RF-CHT group appeared to be free of malignancy and was excluded from the analysis as no tumour biopsies were available. The median MMC concentration in tumour tissue was higher in the RF-CHT group (median 665.00 ng/g vs. 63.75 ng/g, U = 51.0, p = 0.018). Moreover, in both techniques the MMC concentration was lower in normal tissue compared to tumour tissue. Tissue MMC concentration measurements varied substantially within, and between, different patients from the same group.

Intravesical RF-CHT results in higher tumour MMC concentrations vs. cold MMC instillation which contributes to its superior efficacy.

International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. 2017 Dec 01 [Epub ahead of print]

F Johannes P van Valenberg, Antoine G van der Heijden, Rianne J M Lammers, Johannes Falke, Tom J H Arends, Egbert Oosterwijk, J Alfred Witjes

a Department of Urology , Radboud University Medical Center , Nijmegen , The Netherlands.

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