(UroToday.com) The 2025 European Association of Urology (EAU) Annual Congress held in Madrid, Spain between March 21st and 24th 2025, was host to an abstract session on the latest advances in the diagnosis and follow-up of non-muscle invasive bladder cancer (NMIBC). Joep de Jong presented a study evaluating the significance of immune infiltration gene expression signatures as predictive biomarkers of differential response to sequential intravesical gemcitabine plus docetaxel versus Bacillus Calmette-Guerin (BCG) in high-risk NMIBC (HR-NMIBC).
Intravesical BCG remains the guideline-recommended therapy for HR-NMIBC. However, the ongoing global BCG shortage has prompted the investigation of alternative therapeutic options. One such alternative, sequential intravesical gemcitabine and docetaxel (Gem/Doce), has shown comparable efficacy to BCG in the treatment of HR-NMIBC.1 The objective of this study was to use molecular subtyping and immune score stratification as predictive markers of preferential treatment response to BCG versus Gem/Doce treatments.
A matched cohort analysis of 143 patients with treatment-naïve HR-NMIBC from The University of Iowa was performed.1 The study cohort included 92 patients who received BCG and 51 who received Gem/Doce. Gene expression profiling was performed using the Decipher Bladder Genomic Subtyping Classifier (GSC, Veracyte, San Diego, CA), a clinical-grade, transcriptome-wide assay, to determine molecular subtypes. Consensus subtyping models were also applied. Patients were categorized into higher (>median) and lower (<median) ESTIMATE immune scores using the ESTIMATE algorithm (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data). The primary endpoint was high-grade recurrence-free survival (HG-RFS), with Cox-regression and Kaplan-Meier analyses used to evaluate the associations between molecular subgroups and HG-RFS.
Overall, 34% of patients had cTa tumors, 64% had T1-stage tumors, and 2% had Tis alone; 30% had concomitant carcinoma in situ (CIS). There were no significant differences in median patient age, clinical tumor stage, presence/absence of CIS, or molecular subtype distribution between the BCG and Gem/Doce groups (all p>0.5).
The median follow-up was 49 months for BCG-treated patients and 22 months for Gem/Doce-treated patients. High-grade disease recurrence was observed in 36% of BCG-treated patients, compared to 16% of Gem/Doce-treated patients.
In the overall cohort, 85% were classified as GSC luminal and 71% as Consensus luminal papillary subtypes. The median ESTIMATE immune score was 556 (IQR: 126–1410).
Patients with higher immune scores demonstrated superior HG-RFS rates with Gem/Doce compared to BCG (hazard ratio [HR]: 0.25; 95% CI: 0.07–0.85; p=0.02). At the 2-year mark, those with higher immune scores had significantly better HG-RFS with Gem/Doce versus BCG (90% versus 63%, p=0.02). Conversely, for patients with lower immune scores, HG-RFS was similar between Gem/Doce- and BCG-treated patients (86% versus 72%, HR 0.71; 95% CI: 0.26–1.95; p=0.50).
The investigators noted that this study represents the first molecular comparison of treatment-naïve HR-NMIBC patients receiving Gem/Doce versus BCG. Although the majority of the cohort was classified as luminal molecular subtype, substantial variability was observed in immune signature scores at diagnosis. Notably, patients with high immune scores at diagnosis appeared to derive a preferentially greater benefit from Gem/Doce treatment, compared to BCG. These findings warrant further validation in larger cohorts to confirm their potential for guiding treatment selection in HR-NMIBC patients.Presented by: Joep de Jong, BSc, PhD Candidate, Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2025 European Association of Urology (EAU) Annual Congress held in Madrid, Spain between March 21st and 24th, 2025
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