Role of the Combined Regimen with Local Chemotherapy and Mw-Induced Hyperthermia for Non-Muscle Invasive Bladder Cancer Management. A Systematic Review

Abstract

To give an updated review concerning the role of combined regimen (CT) based on microwave-induced hyperthermia (MwHT, CT-MwHT) with intravesical chemotherapy (ICT) as a treatment for non-muscle invasive bladder cancer (NMIBC). The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. An electronic search of the Medline, Embase, Cochrane Library, CancerLit, and ClinicalTrials.gov databases was undertaken. Relevant conference abstracts and urology journals were also included. The primary end-point was the time to recurrence. Secondary end-points included time to progression, bladder preservation rate, and adverse event (AE) rate. A total of 24 studies met inclusion criteria and underwent data extraction. When feasible, data were combined using random-effects meta-analytic techniques. Recurrence was seen 59% less after CT-MwHT than after MMC alone, however, due to the short follow-up, no definitive conclusions can be drawn about the impact on the time to recurrence and progression. The overall bladder preservation rate after CT-MwHT was 87.6%. This rate appeared higher than after MMC alone, but valid comparison studies could not be drawn due to the absence of randomized trials in neo-adjuvant settings. AEs were higher with CT-MwHT than with MMC alone, but this difference was not statistically significant. Published data suggest that recurrence rates for chemo-hyperthermia are substantially reduced compared with chemotherapy alone in adjuvant settings. Patients with refractory disease fare worse than those being treated with chemo-hyperthermia for their first tumor. Progression rates to muscle-invasive disease are markedly lower after combination treatment than after chemotherapy alone, with very high rates of bladder preservation. Tolerability is good, with few dropouts in the clinical trials. The results support CT-MwHT in the future as a standard procedure for high-risk recurrent patients, for subjects in whom the treatment with Bacillus Calmette-Guérin is contraindicated, and those unsuitable for radical cystectomy.