Outcomes and complications of Hyperthermic IntraVesical Chemotherapy using Mitomycin-C or Epirubicin for patients with non-muscle invasive bladder cancer after Bacillus Calmette-Guérin treatment failure

Abstract

Introduction Chemohyperthermia is a feasible option in BCG (bacillus Calmette-Guérin) failure patients who desire bladder preservation. We aimed to assess outcomes and complications of chemohyperthermia using mitomycin C (MMC) or epirubicin (EPI). Material and methods From March 2017 to February 2020, 103 BCG failure or intolerance patients with high-risk NMIBC (non-muscle invasive bladder cancer) underwent a hyperthermic intravesical chemotherapy (HIVEC) regimen. Five patients did not complete at least 5 instillations and were excluded from analysis. MMC was used in 72 out of 98 patients (Group A) while EPI was used in 26 patients (Group B). Response to HIVEC, predictive factors for treatment outcome and the disease-free survival (DFS) were defined as primary endpoints. The complications of chemohyperthermia were assessed as a secondary endpoint. Results No significant differences were found in recurrence and progression after induction course between Groups A and B. Kaplan-Meier disease-free survival was 22.61 months in Group A and 21.93 in Group B. The log-rank test showed no statistically significant difference between the two curves (p = .627). In the multivariate analysis, patients with tumor size ≥3 cm (p = .029), recurrence rate >1/year (p = .034), concomitant carcinoma in situ (CIS) during transurethral resection of bladder (TURB) (p = .039) and BCG-unresponsive status (p = .048) were associated with a worse response to chemohyperthermia. The use of MMC or EPI did not influence the response to treatment (p = .157). A slightly significant higher rate of overall complications (p = .0488) was observed in Group B. A significantly higher rate of Grade 3 frequency/urgency (p = .0064) contributed to this difference. The use of EPI was the only independent factor associated with severe urinary frequency/urgency (p = .017). No patients experienced Grade 4/5 adverse events. Conclusions HIVEC can be considered a feasible option in BCG failure/intolerant NMIBC patients, avoiding or postponing radical cystectomy in some particular subclasses of patients.

Intravesical thermochemotherapy in the treatment of high-risk and very high-risk non-muscle-invasive urothelial bladder cancer: a single-arm study

“…It is important to note that 38% of the patients in our group received only induction treatment without maintenance. Additionally, we included patients with CIS as a prognostic factor, which has been shown to be associated with a poorer response in patients with NMIBC failing after BCG [ 15 ]. Both variables (use of maintenance and presence of CIS) adversely correlated with survival without a HR recurrence in our study.…”

“…Since January 2020, only epirubicin has been utilized. According to the available data, the synergistic effect of a drug (chemotherapy and hyperthermia) was found to be comparable between epirubicin and MMC, both on an experimental and clinical level [ 14 , 15 ]. All instillations were performed with the CombatBRSsystem V2.0 (Combat Medical, Wheathampstead, UK).…”

Hyperthermia intravesical chemotherapy acts as a promising alternative to bacillus Calmette–Guérin instillation in non-muscle-invasive bladder cancer: a network meta-analysis

“…Considering that this NMA focuses on HIVEC with MMC, it puts forward a new perspective: explore the combination of hyperthermia and other chemotherapeutic drugs instead of MMC. It has been found that using MMC or EPI in HIVEC did not influence the response to treatment (p = 0.157) (52). For example, one study found that the therapeutic rank of GEM was superior to that of BCG in their network model (53).…”

Application of intra-arterial chemotherapy in high-risk non-muscle invasive bladder cancer: a systematic review and meta-analysis

“…However, fewer than half completed the cycle of full-dose BCG treatment because of adverse complications (Kulkarni et al, 2007). Subsequently, various treatments were explored, such as new drugs, radiation therapy, and novel chemotherapy approaches including intravenous chemotherapy, IAC and hyperthermic intravesical chemotherapy (Chiancone et al, 2020;Di Lorenzo et al, 2010;Weiss et al, 2006;Yang et al, 2017). The IAC had received attention because of higher chemotherapy concentration in the bladder and lower systemic toxicity compared with intravenous chemotherapy (Eapen et al, 2004).…”