A pilot clinical trial of intravesical mitomycin-C and external deep pelvic hyperthermia for non-muscle-invasive bladder cancer

Abstract

Purpose This paper aims to evaluate the safety and heating efficiency of external deep pelvic hyperthermia combined with intravesical mitomycin C (MMC) as a novel therapy for non-muscle-invasive bladder cancer (NMIBC). Materials and methods We enrolled subjects with bacillus Calmette-Guérin (BCG) refractory NMIBC to an early phase clinical trial of external deep pelvic hyperthermia (using a BSD-2000 device) combined with MMC. Bladders were heated to 42 °C for 1 h during intravesical MMC treatment. Treatments were given weekly for 6 weeks, then monthly for 4 months. Heating parameters, treatment toxicity, and clinical outcomes were systematically measured. Results Fifteen patients were enrolled on the clinical trial. Median age was 66 years and 87% were male. Median European Organisation for Research and Treatment of Cancer (EORTC) recurrence and progression scores were 6 and 8, respectively. The full treatment course was attained in 73% of subjects. Effective bladder heating was possible in all but one patient who could not tolerate the supine position due to lung disease. Adverse events were all minor (grade 2 or less) and no systemic toxicity was observed. The most common adverse effects were Foley catheter pain (40%), abdominal discomfort (33%), chemical cystitis symptoms (27%), and abdominal skin swelling (27%). With a median follow-up of 3.18 years, 67% experienced another bladder cancer recurrence (none were muscle invasive) and 13% experienced an upper tract recurrence. Conclusions External deep pelvic hyperthermia using the BSD-2000 device is a safe and reproducible method of heating the bladder in patients undergoing intravesical MMC. The efficacy of this treatment modality should be explored further in clinical trials.

Effects of hyperthermia in neutralising mechanisms of drug resistance in non-muscle-invasive bladder cancer

“…Further, reoxygenation was associated with better clinical response in the locally advanced breast cancer study [32]. The prescribed temperature range for bladder heating is in the range of [42][43] C [33,34]. Thus it is unlikely that vascular damage to the tumour or normal tissue vasculature is a consequence.…”

Bladder intracavitary hyperthermic perfusion chemotherapy for the prevention of recurrence of non-muscle invasive bladder cancer after transurethral resection

“…Thermochemotherapy combining the direct antitumorigenic effect of local hyperthermia with a potentiated antitumorigenic cytostatic agent improves chemotherapy outcomes (19,30). However, conventional thermochemotherapy procedures do not allow precise and stable temperature control at the lesion sites, which hampers treatment efficacy (31)(32)(33)(34). We developed a 'BR-TRG-I type high-precision hyperthermic intraperitoneal perfusion treatment system', which allows precise automatic control of the temperature and perfusion rate of the drug solution.…”

Chemohyperthermia in non-muscle-invasive bladder cancer: An overview of the literature and recommendations

“…In a pilot clinical trial using the BSD-2000 V R system, Inman et al reported outcomes of 15 patients with BCG refractory NMIBC, treated with external deep pelvic CHT [16]. All patients completed a 6-week induction course of BCG prior to their most recent recurrence, or were intolerant to BCG.…”

“…The most common adverse events related to treatment with the BSD-2000 system were; urethral pain due to Foley catheter placement (40%), abdominal discomfort from the hyperthermia system (33%), irritative urinary symptoms from chemical cystitis (27%), and heat-induced induration or swelling of the abdominal skin (27%) [16].…”

“…Temperature probes, placed intravesically via a Foley catheter (18 Ch) and in the rectum, are used for temperature monitoring and mapping, aiming for a bladder temperature of 42 ± 2 C. The bladder, including MMC, is heated using the four antenna pairs to a temperature of 40 C for at least 40 minutes, but with a maximum total duration of 60 minutes. For adjuvant treatment 40 mg MMC is administered to patients [15][16][17].…”