Sequential bacillus Calmette-Guérin/Electromotive Drug Administration of Mitomycin C as the Standard Intravesical Regimen in High Risk Nonmuscle Invasive Bladder Cancer: 2-Year Outcomes

Abstract

Purpose: Sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C is reported to be superior to bacillus Calmette-Guérin alone but it has not been widely adopted. We aimed to determine the efficacy and tolerability of sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C in high risk, nonmuscle invasive bladder cancer.

Materials and methods: Starting in 2009 bacillus Calmette-Guérin/electromotive drug administration of mitomycin C was introduced as the standard induction regime in patients with high risk, nonmuscle invasive bladder cancer undergoing bladder conservation. As induction bacillus Calmette-Guérin was administered in weeks 1 and 2. Mitomycin C was administered in electromotive fashion (40 mg and 20 mA current for 30 minutes) in week 3 and repeated thrice for a total of 9 weeks. As maintenance 3 doses of bacillus Calmette-Guérin were given 3 months after induction and then every 6 months for 3 years. Outcome measures were disease recurrence at first check, 1 and 2-year cystoscopy, and treatment tolerability.

Results: Of the 151 patients with high risk, nonmuscle invasive bladder cancer treated between June 2009 and 2013, 44 underwent primary cystectomy and 107 received sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C. Disease was high grade Ta/T1 in 86 patients (80%), of whom 34 (32%) also had carcinoma in situ. A total of 19 patients (18%) had primary carcinoma in situ and 2 had recurrent large volume, low grade disease. Of 107 patients 104 underwent first check cystoscopy, including 90 (87%) who were clear. Of the 90 complete responders 86 underwent 1-year cystoscopy, including 74 (86%) who were recurrence-free. Of the 74 patients 71 underwent 2-year cystoscopy, of whom 66 (93%) remained recurrence-free. The full induction schedule was not completed in 30 patients (28%), including 16 and 14 with minor and major schedule alterations, respectively. There was no difference in recurrence between patients who received a full vs a reduced induction schedule.

Conclusions: This study confirms the excellent oncologic efficacy of sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C in cases of high risk, nonmuscle invasive bladder cancer. Tolerability is a challenge but alterations to the 9-week schedule appeared to have a negligible impact on outcomes.

Keywords: Mycobacterium bovis; drug delivery systems; mitomycin; treatment outcome; urinary bladder neoplasms.