(UroToday.com) The 2025 Society of Urologic Oncology (SUO) Annual Meeting was host to a bladder cancer poster session. Dr. Ahmed Eraky presented a study demonstrating that pre-cystectomy ctDNA burden is predictive of poor oncologic outcomes.
Tumor-informed ctDNA is an emerging prognostic biomarker in bladder cancer. The study investigators evaluated whether pre-cystectomy ctDNA detectability and burden predict recurrence after radical cystectomy.
Patients undergoing radical cystectomy between 2021 and 2023 had prospectively collected, tumor-informed ctDNA (Signatera®, Natera Inc.). ctDNA status and tumor molecules/mL (MTM/mL) were derived from the pre-cystectomy sample. ctDNA burden was defined as:
- Low: <2.25 MTM/mL
- High: ≥2.25 MTM/mL
Recurrence-free survival (RFS) was analyzed using Kaplan–Meier methods with Benjamini–Hochberg correction for multiple comparisons. Patients with ≥3 months of follow-up (n=120) were included in the survival analyses.
A total of 137 patients had pre-cystectomy ctDNA available. The median age was 71 years, the median follow-up was 11 months, and recurrence was observed in 40 patients (29.2%).
The frequency of ≥pT3 disease by ctDNA burden was as follows:
- 17% in undetectable ctDNA
- 31.6% in low-burden ctDNA
- 51.6% in high-burden ctDNA (p<0.001)
The frequency of nodal involvement progressively increased with ctDNA burden:
- 9.5% in undetectable ctDNA
- 29% in low burden
- 58.3% in high burden (p<0.001)
ctDNA status was strongly prognostic for recurrence rates:
- Patients with detectable ctDNA had significantly worse RFS, compared to those with undetectable ctDNA (p<0.001).
- Median RFS:
- Not reached (undetectable)
- 11.2 months (low burden)
- 5.2 months (high burden)
On multivariable analysis, adjusted for clinical stage, variant histology, and neoadjuvant therapy, ctDNA burden remained a powerful independent predictor of RFS:
- Low-burden ctDNA: HR 4.88 (95% CI 1.8–13.1), p=0.002
- High-burden ctDNA: HR 10.8 (95% CI 4.2–27.6), p<0.001
Both groups had significantly higher recurrence rates compared to those with undetectable ctDNA levels.
Dr. Eraky concluded that pre-cystectomy ctDNA detectability and burden strongly predict recurrence risk following radical cystectomy. Patients with high-burden ctDNA may benefit from treatment intensification before cystectomy, while those with low-burden ctDNA exhibit intermediate risk and may be candidates for response-adapted perioperative strategies.
Presented by: Ahmed Eraky, MBBCh, FEBU, Society of Urologic Oncology (SUO) Fellow, Mount Sinai Hospital, New York, NY
Written by: Rashid K. Sayyid, MD, MSc, Assistant Professor, Urologic Oncologist, Department of Urology at The University of Arizona and Banner University Medical Center – Tucson, AZ, @rksayyid on X during the 2025 Society of Urologic Oncology (SUO) Annual Meeting, Phoenix, AZ, December 2nd–5th, 2025