Intravesical EMDA/MMC Safe, Feasible for BCG-Unresponsive NMIBC

Bacillus Calmette-Guérin (BCG) therapy is one of the most common intravesical immunotherapies for patients with bladder cancer. For those with non-muscle invasive bladder cancer (NMIBC) who do not experience success with BCG and are unable to undergo cystectomy, intravesical electromotive mitomycin (EMDA/MMC) may serve as a promising option.

Savino Mauro Di Stasi, MD, and colleagues presented their study results at the 2024 American Urological Association Annual Meeting.

A total of 191 patients with BCG-unresponsive NMIBC were enrolled in the study from January 2006 to December 2018. Each patient underwent transurethral resection of bladder tumor (TURBT) and re-TURBT, after which they were scheduled for 6 weekly intravesical EMDA/MMC treatments. Nonresponders were given 6 additional weekly treatments, while responders were given 9 additional monthly treatments.

Patients were followed up every 3 months for the first 2 years, then every 6 months thereafter. The study’s primary end points included complete response (CR; defined by absence of high-risk NMIBC or progressive disease) at 3 months for carcinoma in situ (CIS) and recurrence-free survival for fully resected papillary disease. Secondary end points included disease progression, overall survival, and disease-specific survival.

Of 191 patients, 89 were included in the efficacy and safety analysis. Of these patients, 48 had CIS, while 41 had papillary disease alone. The median follow-up was 40 months.

Of those with CIS, CR was achieved in 23 (47.9% [95% CI, 33.3-62.8]), 26 (54.2% [39.2-68.6]), 19 (39.6% [25.8-54.7]), 12 (25% [13.6-39.6]), and 11 (22.9% [12.0-37.3]) patients at 3, 6, 12, 18, and 24 months, respectively.

Of those with papillary disease alone, 38 (92.7% [95% CI, 80.1-98.5]), 32 (78.1% [62.4-89.4]), 29 (70.7 [54.5-63.9]), 20 (48.8% [32.9-54.9]), and 17 (41.5% [26.3-57.9]) patients were recurrence free at 3, 6, 12, 18, and 24 months, respectively.

Patients with papillary disease alone had lower high-grade recurrence than patients with CIS (24.4% [12.4-40.3] vs 64.6% [49.5-77.4]; log-rank P=.0002). These patients also had more favorable rates of progression (14.6% [5.6-29.2] vs 41.7 [27.6-56.8]; P=.0554), overall mortality (39% [24.2-55.5] vs 68.7% [53.7-81.3]; P=.9379), and disease-specific mortality (4.9% [0.6-16.5] vs 20.8 [10.5-35]; P=.1465).

Intravesical EMDA/MMC can serve as a safe and effective therapy option for patients with high-risk NMIBC who fail BCG therapy. As BCG can result in delayed and longer cell-mediated immunity after immunization, these data warrant further review of existing guidelines for patients with BCG failure.