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IP47-05 A STROMAL TRANSCRIPTOMIC SIGNATURE IS PROGNOSTIC IN HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER TREATED WITH INTRAVESICAL BACILLUS CALMETTE-GUERIN
Abstract   Peer reviewed

IP47-05 A STROMAL TRANSCRIPTOMIC SIGNATURE IS PROGNOSTIC IN HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER TREATED WITH INTRAVESICAL BACILLUS CALMETTE-GUERIN

Vignesh T. Packiam, Ian Mcelree, Saum Ghodoussipour, Melinda Fu, James Proudfoot, Elai Davicioni, Michael O'Donnell and Joep Jde Jong
The Journal of urology, Vol.215(5S), p.e946
05/2026
DOI: 10.1097/01.JU.0001191556.17107.c7.05

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Abstract

INTRODUCTION AND OBJECTIVES: There are increasing available effective therapies for non-muscle invasive bladder cancer (NMIBC), and thus, growing rationale for predictive tools. Several molecular biomarkers have been proposed to improve prediction of outcomes following intravesical Bacillus Calmette-Guerin (BCG) for high-risk (HR) NMIBC, although external validation is lacking. Therefore, herein, we evaluated transcriptomic signatures and molecular subtypes on an independent cohort of patients with HR-NMIBC treated with BCG. METHODS: We assessed a cohort of treatment-naïve HR-NMIBC patients who were treated with BCG. Archived TURBT specimens were analyzed with the Decipher Bladder Genomic Subtyping Classifier (GSC), a clinical-grade transcriptome-wide assay (Veracyte, San Diego, CA). Molecular subtypes using the GSC, consensus-MIBC and UROMOL21 models, and 194 locked transcriptomic signatures in GRID (v3.1) were examined. Cox-regression and Kaplan-Meier analyses adjusted for age, sex, treatment year and CIS were used to evaluate associations between signatures and outcomes including high-grade recurrence-free survival (HG-RFS). RESULTS: Of 92 patients treated with BCG, there were 31 TaHG, 59 T1HG, 2 pure CIS, and 25 with any CIS. Median follow-up was 49 months, and 33 patients had HG disease recurrence. In total, 85% of patients were classified as GSC luminal, 73% as Consensus luminal papillary subtypes, and 50% UROMOL Class 3. UROMOL Class 1 (14%) had best HG-RFS at 3-years (92% versus 61% for non-Class 1). Analysis of tumor microenvironment signatures revealed a stromal gene signature (Efstathiou2018) was associated with worse HG-RFS (p<0.01), PFS (p=0.01) and OS (p=0.03) after BCG. Stromal gene signature scores were highest in GSC Infiltrated or Consensus stroma-rich, and UROMOL21 Class 2b tumors. Several angiogenesis signatures were associated with progression to MIBC (Uhlik2016 p<0.03 & Masiero2013 p<0.02). CONCLUSIONS: This was an extensive transcriptomic analysis of patients with treatment-naïve HR-NMIBC who then received BCG. While the luminal molecular subtype was predominant, there was substantial variation in other tumor biology scores. Notably, high stromal scores were associated with inferior response to BCG. NMIBC-specific subtyping models need to be improved and validated to better predict outcomes.

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