Combination intravesical chemotherapy for non-muscle invasive bladder cancer (NMIBC) as first-line or rescue therapy: where do we stand now?

ABSTRACT

Introduction

The combination of intravesical gemcitabine (Gem) with docetaxel (Doce) or with mitomycin C (MMC) has been used in the primary setting as an alternative to Bacillus Calmette-Guerin (BCG) to treat high-risk (HR) and intermediate-risk (IR) non-muscle invasive bladder cancer (NMIBC), as well in the rescue setting for patients in whom BCG has failed.

Area covered

Efficacy and safety of Gem/Doce and Gem/MMC to treat NMIBC in BCG-naive and failure settings.

Expert opinion

In the BCG-naive setting, Gem/Doce was the primary alternative combination therapy reported, with a weighted mean of 12- and 24-month recurrence-free survival (RFS) of 79% and 77% for HR disease and 84% and 76% for IR disease, respectively. In the HR BCG-failure setting, the weighted mean of 12- and 24-month RFS was 60% and 42% for Gem/Doce and 63% and 40% for Gem/MMC. While patients without BCG exposure and papillary disease only benefit the most from Gem/Doce, there is also reasonable efficacy in BCG refractory disease and CIS. Combination therapy is well tolerated, with grade III toxicity reported in less than 1% of patients. Unlike single-agent chemotherapy, intravesical Gem/Doce is considered effective and safe regardless of risk-stratification.

KEYWORDS:

• Non-muscle invasive
• bladder cancer
• intravesical
• gemcitabine
• docetaxel
• mitomycin C
• BCG failure
• BCG naive

Article highlights

• Due to BCG failure and persistent shortages, treating non-muscle invasive bladder cancer (NMIBC) is difficult in the absence of modern, robust, prospective, randomized comparative testing of viable alternatives.

• Gemcitabine/Docetaxel (Gem/Doce) and Gemcitabine/Mitomycin C (Gem/MMC) have been tested in the treatment of BCG-naive and failure NMIBC cases with promising results.

• Gem/Doce and Gem/MMC are both well-tolerated and effective therapies for BCG-failed NMIBC cases. Additionally, Gem/Doce has shown encouraging outcomes in high-risk BCG-naive cases.

• The combination of intravesical Gem/Doce is equally efficacious as the conventional BCG treatment for intermediate-risk disease.

• Gem/Doce is somewhat less effective (by 10%) for BCG-refractory cases with CIS tumors compared with papillary-only tumors.

Disclosure statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14656566.2024.2310073.

Additional information

Funding

This paper was supported by the John and Carol Walter Family Foundation.