(UroToday.com) The 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between February 13th and 15th 2025, was host to the Poster Session B: Urothelial Carcinoma. Dr. Ian McElree presented Abstract 832: Impact of gene expression signatures of immune infiltration on response to sequential intravesical gemcitabine and docetaxel versus bacillus Calmette-Guerin in high-risk non-muscle-invasive bladder cancer.
Dr. McElree began his presentation by highlighting that Bacillus Calmette-Guérin (BCG) remains the standard of care for high-risk non-muscle-invasive bladder cancer (HR-NMIBC) following transurethral resection of bladder tumor (TURBT). However, due to ongoing BCG shortages, sequential intravesical gemcitabine and docetaxel (Gem/Doce) has been increasingly adopted as a first-line treatment option for HR-NMIBC. Given this shift, appropriate patient selection is crucial, and biomarkers are needed to guide treatment decisions.
The aim of the investigators was to evaluate the association between molecular subtypes, immune signature scores, and high-grade recurrence-free survival (HG-RFS) in patients with treatment-naïve HR-NMIBC who were treated with BCG or Gem/Doce as well as to identify potential
biomarkers for improving treatment selection.
This was a retrospective analysis of a matched cohort of 143 treatment-naïve HR-NMIBC patients treated at the University of Iowa with either:
- BCG (n=92)
- Gem/Doce (n=51)
The investigators analyzed archived tumor specimens from a matched cohort of patients who had undergone TURBT. These specimens were evaluated using the Decipher Bladder Genomic Subtyping Classifier (GSC, Veracyte, San Diego, CA), a clinical-grade whole-transcriptome assay that employs machine-learning algorithms to classify bladder tumors into five molecular subtypes, each with distinct biological characteristics.
For this analysis, tumors were molecularly subtyped using both the GSC and Consensus subtyping models. Additionally, immune signature analysis was performed using the ESTIMATE algorithm, which generated immune scores to stratify patients into higher (above the median) and lower (below the median) immune score groups. The primary endpoint of the study was high-grade recurrence-free survival (HG-RFS).
A total of 143 patients were included in the matched cohort. Tumor stage, presence of CIS, and molecular subtype distributions were comparable between BCG and the Gem/Doce groups (all p>0.5). Notably, 85% of tumors were classified as GSC luminal and 71% as Consensus luminal papillary subtypes. The median ESTIMATE immune score was 556 (IQR: 126–1410).
The median follow-up was 49 months for the BCG group and 22 months for the Gem/Doce group. For the primary endpoint, high-grade recurrences occurred in 36% of patients treated with BCG compared to 16% of those treated with Gem/Doce. At two years, HG-RFS was significantly better in patients with a higher immune score who received Gem/Doce versus BCG (90% vs. 63%), with a hazard ratio (HR) of 0.25 (P=0.02). However, outcomes were similar in patients with lower immune scores (HR 0.71, P=0.50). These results are illustrated in the Kaplan-Meier curves below.
Dr. McElree concluded that higher immune scores are associated with superior HG-RFS in patients treated with Gem/Doce compared to BCG, highlighting the potential role of immune signatures as biomarkers for treatment selection in HR-NMIBC.
Presented by: Ian McElree, MD at the University of Iowa Carver College of Medicine, Iowa City, Iowa City, IA.
Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025
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