(UroToday.com) The American Urological Association (AUA) 2025 Annual Meeting, held in Las Vegas, NV, was host to a non-invasive bladder cancer podium session. Dr. John Ogunkeye presented a study evaluating the performance of minimal residual disease detection with urine-derived DNA in high-grade bladder cancer patients undergoing a recommended repeat TURBT.
The current AUA guidelines recommend a repeat TURBT for high-risk NMIBC due to the risk of residual disease following endoscopic resection and concerns about disease understaging. However, identifying candidate patients who potentially benefit most from a repeat TURBT remains a clinical challenge – are there T1 patients that can avoid a re-resection, and which Ta patients require a re-resection? The study objective was to evaluate whether urine tumor DNA following a TURBT can predict the presence of residual disease on a restaging TURBT.
UroAmp is a Clinical Laboratory Improvement Amendments (CLIA)-certified urine test. Urine is collected from patients, after which DNA extraction and next-generation sequencing (NGS) are performed. This urine test has previously been evaluated in the work up of microscopic hematuria and for bladder cancer surveillance. A urine comprehensive genomic profile is generated, and an artificial intelligence (AI) machine learning algorithm provides:
- Binary metric: Residual disease (present/absent)
- Quantitative metric: How much residual disease is present
The threshold for a ‘positive’ test is defined based on the Genomic Disease Burden (GDB), which is a % ranking of tumor DNA burden (0–100%). The GDB cutoff can be adjusted to optimize for sensitivity or specificity.
This was a retrospective study of 55 patients with a median age of 73 years. 16% of patients had received prior intravesical therapy, 22% of tumors harbored variant histology, 80% were NMIBC patients, and 20% had received bladder-preservation for MIBC.
The study investigators used banked urine obtained after a TURBT from either Stanford Hospital or Palo Alto VA. The objective of the study was to evaluate the performance characteristics of UroAmp for detecting residual disease following the initial TURBT, using repeat TURBT pathology as the gold standard.
Dr. Ogunkeye gave a case presentation of a 79-year-old-male with HG T1 disease at the bladder neck, who underwent a TURBT.
He had a UroAmp positive result following the initial TURBT, despite having no residual disease on repeat TURBT (i.e., a false positive finding).
He received intravesical therapy, and 10 months later, on surveillance cystoscopy, was found to have a prostatic urethral lesion.
However, on re-evaluation of the recorded initial TURBT, the patient was retrospectively noted to have had a small prostatic urethral lesion that was missed on the initial endoscopic evaluation. As such, UroAmp would have provided a 10-month lead-time benefit in such a case scenario.
The initial and repeat TURBT pathology findings for this cohort are summarized below. Notably, 34% of patients had negative findings on repeat TURBT (i.e., T0).
Overall, the performance characteristics of UroAmp were as follows:
- Sensitivity: 92%
- Specificity: 60%
- PPV: 82%
- NPV: 80%
Among the T1 patients (n=38), UroAmp performed as follows:
- Sensitivity: 97%
- NPV: 88%
- Sensitivity in patients upstaged to MIBC (n=5): 100%
- As such, Dr. Ogunkeye argued that UroAmp may be helpful to de-escalate care in high surgical risk patients
Among the Ta patients (n=6), the specificity was notably only 66%. He noted that UroAmp’s modest specificity in this setting may result in too many false-positives to use this test as a rule-in test for Ta patients. However, altering the GDB threshold for these patients, as illustrated below, may be the key to maximizing the performance of this test in the Ta population.
What about the false positives? Overall, there were 8 false positive test findings. Of these 8 patients, 6 had pathologically confirmed recurrences (5/6 within the 1st 2 years). If we account for long-term follow-up (24 months), the specificity and PPV improve as follows:
- Specificity: 60% 80%
- PPV: 82% 93%
- As such, Dr. Ogunkeye argued that UroAmp testing may be helpful in identifying residual disease when pathology is negative
Notable limitations to this study include:
- Retrospective nature
- Small sample size with limited long-term follow-up
- No comparison with currently available urine tests (i.e., urine cytology)
Dr. Ogunkeye concluded his presentation as follows:
- Urine tumor DNA predicts residual disease following TURBT
- UroAmp can be helpful for:
- De-escalation of care in high surgical risk T1 patients
- Escalation of care in Ta patients using GDB threshold
- Positive UroAmp + negative repeat TURBT
- May be an indicator of persistent residual disease not visible on endoscopic evaluation
- Longitudinal testing is valuable in these cases
Presented by: John Ogunkeye, MD, Resident Physician, Department of Urology, Standard University, Stanford, CA
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