(UroToday.com) The American Urologic Association (AUA) 2025 Annual Meeting held in Las Vegas, NV between April 26th and 29th, 2025 was host to a non-invasive bladder cancer interactive poster session. Dr. Henning Bahlburg presented an analysis evaluating UroAmp MRD for predicting recurrences in high-risk non-muscle invasive bladder cancer (NMIBC) patients receiving intravesical BCG therapy.
Intravesical BCG remains the ‘gold standard’ adjuvant therapy for the treatment of select intermediate- and high-risk NMIBC patients. However, ~25% of patients recur within the initial 12 months, despite receiving ‘optimal’ therapy. The identification of patients at increased risk of recurrence could inform subsequent treatment decision-making. Somatic genomic profiling using next-generation sequencing (NGS) of urine DNA has shown promising results for predicting recurrence rates following intravesical BCG therapy and may allow for a risk-adapted management of NMIBC patients.
This was a study of patients undergoing BCG treatment at two institutions (Vancouver & Helsinki), who had a prospective collection of urine supernatant before the 1st (BCG1) and 6th induction instillations (BCG6) and at the 1st surveillance cystoscopy (CYSTO1). The sequencing and classification were as follows:
- Targeted NGS of 60 genes and shallow whole genome aneuploidy (UroAmp platform, Convergent Genomics)
- Classification as minimal residual disease (MRD) positive or negative was based on a previously validated tumor-naïve algorithm; additional assignment of genomic disease burden (GDB), a percentile rank of the number of detected mutations and their variant allele frequency (VAF)
- Additional exploration of two additional molecular classifications:
- “Biopsy Now”, in which a very high-risk status is defined as GDB >50
- “Longitudinal Recurrence MRD”
- Positive: persistent positive longitudinal MRD (pre- and post-treatment) or pre-treatment VAF >10%
- Negative: persistent negative longitudinal MRD or MRD clearance (positive MRD, negative MRD)
Kaplan-Meier analyses were performed to investigate 18-months recurrence-free survival (RFS) between MRD +/- groups at BCG1 and CYSTO1 (or BCG6), and for Biopsy Now and Molecular Recurrence groups. A potential lead time benefit was investigated.
Overall, 135 samples (BCG1 n=58, BCG6 n=42, and CYSTO1 n=33) from 58 patients were analyzed. MRD was detected in 57% (n=33) of patients at BCG1, 43% (n=18) at BCG6, and 29% (n=10) CYSTO1.
Patients who were MRD-positive at CYSTO1 (or BCG6) or who had a "Biopsy Now" or Longitudinal Recurrence status of positive showed significantly poorer RFS, compared to patients who were MRD-negative (p<0.001).
Among patients with positive MRD status post-intravesical therapy, 6 had identified recurrence lead time (defined as MRD positive ahead of standard of care) within 18 months (7 at any available time). Two patients had positive MRD status without identifiable recurrence during follow-up.
For recurrent patients with positive MRD post-intravesical therapy, a median recurrence lead time of 5.6 months was observed.
Overall, these results suggest the following:
- Despite visually complete resection at time of TURBT, more than half of samples were MRD positive at baseline, with diverse urinary mutations and degrees of genomic severity.
- Longitudinal recurrence status was a strong predictor of RFS, indicating that longitudinal testing can identify molecular responders and allows for greater prognostication of patients than testing at a single time point.
- Urine MRD detection predicted early recurrence in patients following BCG treatment. Notably, a significant portion of recurrent patients ultimately underwent a radical cystectomy (35%, 6/17).
- Integrating urine MRD testing into care pathways could enable more personalized treatments, including informing therapy modifications, earlier surgical intervention, risk stratification, and surveillance intensity.
- Overall, these findings suggest that urine MRD can both identify patients at high risk of recurrence and reliably detect early disease recurrence.
- Further interventional studies are needed to determine the clinical impact of MRD-guided approaches.
Presented by: Henning Bahlburg, MD, Resident Physician, Department of Urology at Marien Hospital Herne, University Hospital of the Ruhr-University, Bochum, Germany
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2025 American Urological Association (AUA) annual meeting held in Las Vegas, NV, Saturday, April 26 - Tuesday, April 29, 2025