REAL-WORLD EFFICACY OF ADJUVANT INTRAVESICAL GEMCITABINE FOR NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC)

Mohamad Abou Chakra; Vignesh T. Packiam; Michael A. O'Donnell

doi:10.1016/j.urolonc.2024.01.164

Failure, intolerance, or shortage of Bacillus Calmette-Guerin (BCG) treatment for patients with high-risk (HR) non-muscle invasive bladder cancer (NMIBC) leaves many facing the prospect of radical cystectomy (RC) as their primary guideline-recommended option. Despite a lack of large-scale randomized controlled studies, single-agent intravesical gemcitabine (Gem) has become a frequently utilized salvage treatment after BCG failure or even first-line alternative to upfront BCG, especially in the general urological community. However, the real-world efficacy of Gem is unclear, as reported 12-month recurrence rates range considerably from 10-82% in BCG failure cohorts treated with Gem. Thus, herein, we aim to stratify reported response rates by clinicopathologic and treatment features in patients who received adjuvant intravesical Gem for HR-NMIBC. We performed a comprehensive literature review to assess the efficacy and safety of adjuvant single-agent intravesical Gem. We searched electronic databases, including PubMed and Scopus, for published studies with the Medical Subject Heading (MeSH) of 'intravesical gemcitabine’ (AND) ‘non-muscle invasive bladder cancer.’ The search was limited to English-language journals and full papers only. The initial search resulted in 250 articles, from which 23 independent studies between 2000 and 2023 relevant to our aims were identified. Data extraction was performed, capturing treatment regimen, percent CIS and papillary disease, AUA risk category, BCG failure type, recurrence-free survival (RFS) at 12 and 24 months, progression rate (PR), and cystectomy rate (CXR). From this data, pooled cohorts were formulated based on AUA risk status, the presence of CIS, and BCG exposure. Efficacy outcomes were estimated using a weighted mean approach. Four primary pooled NMIBC cohorts were defined by predominant characteristics: (1) HR BCG-refractory CIS; (2a) HR BCG-refractory papillary; (2b) Intermediate-risk (IR)/HR BCG-exposed papillary; (3) IR/Low-risk (LR) BCG-exposed papillary; and (4) IR BCG-naïve papillary. Clinicopathologic and treatment characteristics and weighted mean outcome variables by treatment groups were compiled (Table 1). We observed that outcomes were the worst in Group 1 with regard to poor durable DFS and high PR and CXR. Despite a similar pattern of BCG refractoriness, patients in Group 2 with papillary predominant disease had reasonable durable DFS but a PR and CXR rate commensurate with their risk category HR (2a) > IR (intermediate-risk, 2b). Patients in Group 3 had poor DFS, while those in Group 4 who were BCG naïve had high RFS and minimal PR. Categorization based on AUA risk status, the presence of CIS, and the degree of BCG exposure demonstrated expected recurrence and progression rates for Gem. As expected, the best DFS results for Gem were found in patients with favorable characteristics: predominantly papillary disease, minimal or no CIS, AUA low or intermediate risk, and low to no prior BCG exposure. Conversely, cohorts with predominant HR BCG-refractory CIS had the poorest outcomes with respect to DFS, progression, and cystectomy. Interestingly, reasonable DFS was observed in patients with BCG-refractory papillary disease. This analysis is limited by the inclusion of cohorts with a relatively small sample size and a lack of control arms. The efficacy of single-agent Gem in even HR BCG-refractory papillary disease has implications for further well-designed prospective studies in this space.

REAL-WORLD EFFICACY OF ADJUVANT INTRAVESICAL GEMCITABINE FOR NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC)

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