Current and investigational bladder-sparing treatments have only “moderate” efficacy against nonmuscle-invasive bladder cancer (NMIBC) following bacillus Calmette-Guérin (BCG) failure, according to a review published in The Journal of Urology.

Michael Ahdoot, MD, of Cedars-Sinai Medical Center in Los Angeles, California, and colleagues conducted a review of 70 studies involving 27 treatments published from 1998 to 2021. Treatment categories included intravesical chemotherapy, combination therapy, hyperthermia with intravesical chemotherapy, immunotherapy, and novel agents.

Single and combination intravesical chemotherapy had complete response rates that ranged from 10% to 83% at 12 months. Combined gemcitabine plus docetaxel is a commonly used regimen.

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Based on limited data, hyperthermia with chemotherapy demonstrated more favorable 12-month complete response rates of 50% to 85%. However, progression occurred in up to 18% of patients.

Systemic immunotherapeutic agents included pembrolizumab or interferon-α with or without BCG. For pembrolizumab alone, the complete response rate was 21% at 12 months in 1 trial. There were no 12-month data on pembrolizumab plus BCG. Interferon-α plus BCG had 12-month complete response rates of 54% to 63% and 24-month rates of 45% to 66%. Progression rates at 12 months with immunotherapy were 7% to 22%.

Novel agents demonstrated a range of complete response rates from 6% to 91% at 12 months, depending on the agent. N-803 and gene therapy show promise, according to Dr Ahdoot and colleagues. N-803 plus BCG had a complete response rate of 71% at 24 months for patients with carcinoma in situ and 48% at 24 months for patients with papillary features. The novel gene therapy nadofaragene firadenovec had a 12-month complete response rate of 29% to 35%.

The investigators cautioned that this systematic review could not account for all clinically relevant variables influencing NMIBC recurrence.

Grade 3 toxicity rates ranged from 0% to 55% for intravesical chemotherapy and combination intravesical chemotherapy agents, 0% to 15% for hyperthermia with chemotherapy, 12% to 13% for immunotherapy, and 0% to 17% for novel agents. Hematuria, dysuria, urinary frequency, and urinary urgency were frequently reported.

“Given the moderate early success rates and the limited toxicities of several of the preclinical drugs discussed, some of these treatments may reach clinical use in the coming years,” the investigators wrote.

In an accompanying editorial, Padraic O’Malley, MD, and Paul L. Crispen, MD, of University of Florida at Gainesville, called the review “excellent,” but noted that success rates for treating NMIBC after BCG failure need to improve.

“Despite the tremendous efforts by the investigators leading, and the patients participating, in the studies reviewed, only marginal improvements in durable response rates have been gained over time,” they wrote. “Thankfully, there is great promise in the multiple therapeutics that are in development and undergoing evaluation in current trials.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Nazmifar M, Williams C, Naser-Tavakolian A, et al. Clinical and preclinical therapies for bladder cancer following bacillus Calmette-Guérin failure. J Urol. 209(1):32-48.doi:10.1097/JU.0000000000002957

O’Malley P, Crispen PL. Editorial comment. J Urol. 209(1):47-48.

This article originally appeared on Renal and Urology News