(UroToday.com) The 2025 SUO annual meeting featured a urothelial carcinoma session and a presentation by Dr. Vincent D'Andrea discussing genomic signatures predictive of high grade recurrence in non muscle invasive bladder cancer following BCG treatment. Non muscle invasive bladder cancer exhibits a variable clinical course, and current guidelines recommend treatment based on staging and non-genomic risk factors. Genomic profiling may identify molecular drivers of recurrence, refining risk stratification and informing biology-guided therapeutic decisions. At the 2025 SUO annual meeting, Dr. D’Andrea and colleagues identified genomic alterations that are predictive of high-grade recurrence following treatment with BCG, which may assist with risk stratification and subsequent treatment in non muscle invasive bladder cancer.
A Memorial Sloan Kettering Cancer Center database of non muscle invasive bladder cancer patients undergoing treatment was queried on cBioPortal to identify a cohort who had undergone BCG treatment. This cohort was further stratified to identify patients with high-grade recurrence within 12 months and those whose recurrence occurred after 12 months or not at all. Survival differences were assessed using a log-rank test. Genomic alterations at the patient level were identified and compared using a two-sided Fisher Exact test.
There were 503 patients included in the analysis, of which 195 (39.8%) had high-grade recurrence within 12 months, and 308 (61.2%) had high-grade recurrence after 12 months or not at all. Patients with high-grade recurrence within 12 months had a significant reduction in 10 year overall survival compared to patients with high-grade recurrence after 12 months or not at all (HR 2.25, 95% CI 1.15-4.41; p < 0.001):
Genomic alterations were compared between the group with high-grade recurrence within 12 months and the group with high-grade recurrence after 12 months or not at all. Enrichment of the following gene alterations was seen in tumors with high-grade recurrence within 12 months compared to tumors with high-grade recurrence after 12 months or not at all (p < 0.05): CDKN2A/p16/INK4A (35.8% versus 19.2%), CDKN2A/p14/ARF (35.1% versus 19.6%), CDKN2B (24.1% versus 8.1%), and KMT2A (14.9% versus 8.1%). Enrichment of the following gene alterations was seen in tumors with high-grade recurrence after 12 months or not at all versus tumors with high-grade recurrence within 12 months (p < 0.05): PIK3CA (26.3% versus 17.4%) and BRCA1 (6.8% versus 2.6%):
Dr. D'Andrea concluded his presentation discussing genomic signatures predictive of high grade recurrence in non muscle invasive bladder cancer following BCG treatment with the following take home points:
- Genomic signatures predict high grade recurrence in non muscle invasive bladder cancer following BCG treatment, highlighting underlying biological differences not captured by standard clinical risk factors
- Alterations in CDKN2A, CDKN2B, and KMT2A are enriched in early recurrences, suggesting these mutations may drive a more aggressive disease phenotype
- PIK3CA and BRCA1 alterations appear protective, supporting their potential role as modifiers of disease course and warranting further mechanistic and clinical investigation
Presented by: Vincent D. D'Andrea, MD, Dana Farber Cancer Institute, Boston, MA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 Society of Urologic Oncology (SUO) annual meeting held in Phoenix, AZ, between the 2nd and 5th of December 2025.