(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. Darren Lam presented Abstract 847: Determining an immunohistochemical profile to predict response to intravesical bacillus Calmette–Guérin (BCG) in patients with high-grade non-muscle invasive bladder cancer.
Intravesical Bacillus Calmette–Guérin (BCG) remains the gold standard for managing high-grade non-muscle invasive bladder cancer (NMIBC). However, up to 70% of patients experience BCG failure. The investigators aimed to identify potential mechanisms of BCG resistance and develop an immunohistochemical (IHC) panel to predict patient response to intravesical BCG.
Patients with NMIBC undergoing induction intravesical BCG at a tertiary institution were identified. Of these, 12 BCG responders and 13 non-responders were matched according to patient and tumor characteristics.
RNA sequencing was performed, followed by hierarchical clustering and Gene Set Enrichment Analysis to identify mechanisms of response and resistance. Immune cell subsets were analyzed pre- and post-BCG induction therapy using CD4, CD8, T-Bet, GATA-3, and PD-1 antibodies. GATA-3 and T-Bet staining served as surrogates for Th2 and Th1 cells, respectively. Differences between groups were assessed using t-tests. Moreover, an integrated IHC panel using CD4, CD8, T-Bet, GATA and PD1 was developed and correlated with BCG response using Receiver Operator Characteristic (ROC) curves.
Dr. Lam reported that on the hierarchical clustering analysis, BCG-responders and non-responders had distinct gene expression profiles prior- and post-BCG induction.
Prior to exposure to BCG, non-responders compared to BCG-responders had:
- Enrichment for a pro-inflammatory gene signature with a higher CD4:CD8 ratio (2.94 vs 1.71, p=0.0003), respectively.
- Higher Th-2/Th-1 (GATA/T-Bet) ratio (5.95 vs 2.97, p=0.0026).
Upon exposure to BCG, non-responders showed no changes in the CD4:CD8 or Th2/Th1 ratios but exhibited a 78% increase in PD-1 expression (p=0.016), suggesting T-cell exhaustion. In contrast, responders demonstrated an increased Th2/Th1 ratio (mean difference: 0.9323, p=0.0228) and enrichment of the natural killer cell pathway compared to non-responders (p<0.05). The integrated IHC panel predicting BCG response achieved an area under the ROC curve of 0.864 (95% CI: 0.663–1.000).
Dr. Lam concluded their poster with the following messages:
- BCG non-responders had a pro-inflammatory tumor microenvironment, which showed marked T cell exhaustion on exposure to BCG.
- On the other hand, responders to BCG had a baseline tumor microenvironment with low CD4:CD8 and low Th-2/Th-1 ratios at baseline, which allowed activation of both humoral and adaptive responses to BCG.
- These immune changes can be utilised as an IHC panel to inform and predict. response to BCG intravesical treatment.
Presented by: Darren Lam, MD, Monash Medical Centre, Melbourne, Victoria, Australia.
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.