Real-world efficacy of adjuvant single-agent intravesical gemcitabine for non-muscle invasive bladder cancer

ABSTRACT

Introduction

Failure, intolerance, or shortage of bacillus Calmette-Guerin (BCG) treatment for patients with high-risk (HR) non-muscle invasive bladder cancer (NMIBC) leave many facing the prospect of radical cystectomy (RC). However, despite the lack of large-scale randomized controlled studies with single-agent intravesical gemcitabine (Gem), it has emerged as a popular salvage agent after BCG failure or even a treatment alternative to BCG.

Areas covered

1. Characterization of treatment regimen details pertaining to single-agent intravesical adjuvant Gem use among disease states of NMIBC characterized by risk and BCG exposure. 2. Comparison of safety and efficacy of Gem according to risk category, type of tumor (papillary vs. carcinoma in situ (CIS)), and tumor grades.

Expert opinion

Two randomized studies in early BCG failure disease demonstrate that single-agent Gem has superior efficacy versus repeated BCG therapy or mitomycin C. Studies enrolling patients with predominantly papillary disease without CIS, intermediate-risk (IR) disease, and less BCG exposure appear to derive the highest benefits from adjuvant Gem in terms of recurrence and progression. However, studies with cohorts enriched for a predominance of CIS, HR disease and/or more extensive BCG failure have poorer 2-year recurrence free survival and a somewhat higher risk of progression and RC.

KEYWORDS:

• Non-muscle invasive
• bladder cancer
• BCG therapy
• intravesical
• chemotherapy
• gemcitabine
• BCG failure

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Article highlights

• Management of non-muscle invasive bladder cancer is challenging due to BCG failure and chronic shortages without contemporary rigorous prospective randomized comparative testing of potential alternatives.

• Evidence supporting the use of intravesical gemcitabine (Gem) has been growing, although multiple small non-comparative trials show heterogenous outcomes.

• There is good efficacy to Gem in patients with intermediate-risk disease, regardless of BCG exposure.

• Two randomized clinical trials have demonstrated that Gem has comparable efficacy versus repeat BCG and MMC among first-time BCG failures, especially with predominantly papillary disease.

• Among more severe BCG failure groups (BCG unresponsive, BCG refractory, BCG relapsing), patients with predominantly papillary disease have superior efficacy relative to those with predominant CIS.

• Gem is generally well tolerated with easily manageable side effects and a low incidence of severe reactions.

• Current evidence suggests bladder preservation after intravesical Gem has acceptable outcomes especially in well-selected patients with BCG failure without concomitant CIS.

Declaration of interest

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.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14656566.2023.2271396

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.