Electromotive Drug Administration of Mitomycin C (EMDA/MMC) versus Intravesical Immunotherapy with Bacillus Calmette-Guérin (BCG) in Intermediate and High Risk Non Muscle Invasive Bladder Cancer

Abstract

<b><i>Background:</i></b> Although TURB of tumor (TURBT) by itself can eradicate a non-muscle-invasive bladder cancer (NMIBC) completely, these tumors commonly recur and can progress to MIBC. It is, therefore, necessary to consider adjuvant therapy in most patients. The primary objective of the present study was to report our experience with EMDA/MMC and BCG, considering efficacy, progression, and recurrence, as adjuvant therapy in NMIBC patients; the secondary objective was to assess the efficacy of EMDA/MMC versus BCG as a comparative treatment. <b><i>Methods:</i></b> Between April 2016 and February 2020, a series of 216 patients, with a diagnosis of intermediate- and high-risk NMIBC after TURBT, underwent adjuvant intravesical therapy. In 26 cases with a failure of the treatment, in patients unfit and unwilling for radical cystectomy, a repeated intravesical therapy was performed (2 had a twice repetition). Out of 244 adjuvant therapies, 140 EMDA/MMC and 104 BCG treatments were done. The following data were collected for each patient: baseline demographics and clinical data and perioperative and postoperative data. Overall patients’ adjuvant intravesical therapies were included in a prospectively maintained institutional database, and a retrospective chart review was performed. We collected data on 2 main outcomes, recurrence-free survival (defined as a negative cystoscopy, cytology, and/or histology at the evaluation time point) and progression-free survival (defined as a negative cystoscopy or a nonprogressive tumor recurrence). <b><i>Results:</i></b> The NMIBC progression rate was higher in BCG than EMDA/MMC but not statistically significant (respectively, 4.2% vs. 2.5%; <i>p</i> = 0.703). In the overall population, the risk of NMIBC recurrence was higher after BCG than EMDA/MMC (<i>p</i> = 0.025). In the subgroups of 59 paired patients with similar characteristics, no difference was observed between groups in NMIBC progression and recurrence. <b><i>Conclusions:</i></b> Our findings suggest that EMDA/MMC and BCG are safe and reproducible approaches as adjuvant treatment in NMIBC. EMDA/MMC permits to achieve a fine oncological management as adjuvant treatment in NMIBC, which is not less than that obtained with BCG.

Device-assisted intravesical chemotherapy treatment for nonmuscle invasive bladder cancer: 2022 update

“…Short-term (10 months) oncologic results after EMDA [24 ▪▪ ] in comparison to BCG showed a statistical significant lower recurrence rate in favor of EMDA (14.3% (20 pts.) vs. 24% (25 pts.…”

“…Nine studies that investigated HIVEC (oncological outcomes were reported for 1137 patients and AEs for 970 patients) were included for final evaluation after fulfilling the inclusion criteria [13 ▪▪ ,14 ▪▪ ,15 ▪▪ ,16 ▪▪ ,17 ▪▪ ,18 ▪▪ ,19 ▪ ,20 ▪▪ ,21 ▪▪ ]. Another three studies were additionally analyzed: two of them reported outcomes after radiofrequency-induced HIVEC [22 ▪▪ ,23 ▪▪ ], and one after EMDA [24 ▪▪ ]. A summary of the most frequently used devices for intravesical administration of chemotherapy and their characteristics are presented in Table 1.…”

“…Brummelhuis et al [22 ▪▪ ] reported a 10.2% rate severe AEs with 9.4% needing to stop the treatment; on the other hand, Efiloğlu et al [23 ▪▪ ] reported only moderate and mild AEs with only one patient discontinuing the treatment due to AEs. Regarding AEs after EMDA, Zazzara et al [24 ▪▪ ] reported only grade I AEs in 7 (5%) out of the 140 included patients (Table 4).…”

Local Drug Delivery in Bladder Cancer: Advances of Nano/Micro/Macro-Scale Drug Delivery Systems

“…This electromotive technology improved the uptake of mitomycin C after instillation compared with passive transport [ 93 , 94 ], and a 5-year and 10-year cost-effectiveness study concluded that electromotive mitomycin C administration is a cost-effective treatment for patients with high-risk NMIBC [ 95 ]. Electromotive drug administration represents a viable option in patients with BCG-unresponsive NMIBC and reduces the risk of NMIBC recurrence [ 96 , 97 ]. A recent study comparing the efficacy of radiofrequency-induced mitomycin C therapy and electromotive mitomycin C administration showed no differences in the recurrence-free rate at 12 months, toxicity, and adverse effects [ 98 ].…”

Electromotive Enhanced Drug Administration in Oncology: Principles, Evidence, Current and Emerging Applications

“…EMDA protocols adopted by the various centers show slight variations, with earlier studies using a lower current amplitude of 15 mA over shorter time periods of 20 min, while most subsequent studies utilize a maximum of 20 to 23 mA of pulsed DC applied over a duration of 30 min [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. No differences in tolerability and adverse side effects were observed with the higher amplitude and longer durations.…”