Sequential administration of Bacillus Calmette-Guerin (BCG) and Electromotive Drug Administration (EMDA) of mitomycin C (MMC) for the treatment of high-grade nonmuscle invasive bladder cancer after BCG failure.

There is a need for effective nonsurgical treatment options in patients with nonmuscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Guerin (BCG) therapy has failed.

We aimed to determine the efficacy of Electromotive Drug Administration (EMDA) of mitomycin C (MMC) with NMIBC after BCG failure.

A retrospective review of 26 NMIBC patients in whom BCG therapy failed who received BCG/EMDA-MMC between 2013 and 2017 was performed. All but 4 patients fulfilled the FDA criteria for BCG unresponsive disease. Progression and recurrence-free survival (RFS)were calculated using Kaplan-Meier curves. Progression was defined as development of muscle invasive disease, presence of metastasis on imaging or treatment. We used FDA-defined criteria as complete response (CR) for single-arm trials of BCG-unresponsive patients.

Twenty-six patients were included. Initial pathology was carcinoma in situ (CIS) in 53.8% (14/26), pT1 in 34.6% (9/26), and pTa HG disease in 11.6% (3/26). Twelve of 26 patients progressed (46.2%). Following BCG/EMDA-MMC treatment, progression-free survival rates were 58.3% (95% confidence interval [CI] 41.1-82.1) at 1 year and 48.9% (95% CI 48.9) at 2 years from the date of induction of BCG/EMDA-MMC, respectively. RFS was 41.9% (95% CI 25.9-67.8) at 1 year and 27.2% (95% CI 13.6-54.4) at 2 years. CR at 6, 12, and 18 months was observed in 16 (61.5%), 11 (44.0%), and 7 patients (30.4%), respectively. Side effects included dysuria (19.2%), hematuria (19.2%), and frequency (11.5%). Three patients were admitted for side effects but managed conservatively. Four patients (15.4%) died of bladder cancer over the course of the study.

EMDA-MMC BCG represents a viable option in patients with BCG unresponsive NMIBC with close to 50% progression-free survival at 2 years. However, these patients have a high risk of death from bladder cancer (15% in our cohort at 2 years) thus warranting extremely close surveillance.

Urologic oncology. 2020 Jul 22 [Epub ahead of print]

Tristan Juvet, Andrea Mari, Katherine Lajkosz, Christopher Jd Wallis, Cynthia Kuk, Annette Erlich, Lior Krimus, Neil E Fleshner, Girish S Kulkarni, Alexandre R Zlotta

Department of Surgical Oncology, Urology. University Health Network, Toronto, ON, Canada., Department of Urology, University of Florence, Florence, Italy., Department of Surgical Oncology, Urology. University Health Network, Toronto, ON, Canada; Department of Biostatistics, University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada., Department of Surgery, Urology, Sinai Health System, Mount Sinai Hospital, Toronto, ON, Canada., University of Toronto, Faculty of Medicine, University of Toronto, Toronto, ON, Canada., Department of Surgical Oncology, Urology. University Health Network, Toronto, ON, Canada; Department of Surgery, Urology, Sinai Health System, Mount Sinai Hospital, Toronto, ON, Canada. Electronic address: .