Perioperative circulating tumor DNA provides prognostic value in muscle-invasive bladder cancer across both pure urothelial carcinoma and histological subtypes, sharpening recurrence risk predictions after radical cystectomy, according to a study published on August 12, 2026, in European Urology Focus.
Evaluating ctDNA Across Mount Sinai Cohort Histologies
A retrospective review analyzed a prospectively maintained database of consecutive patients with nonmetastatic muscle-invasive bladder cancer. These patients underwent robot-assisted radical cystectomy at Mount Sinai Hospital between November 2021 and May 2025.
The study, authored by Pierre-Etienne Gabriel, Alec Zhu, Christopher Karim, Ahmed Eraky, Raghav Gupta, Reuben Ben-David, Peter Wiklund, Reza Mehrazin, and John P. Sfakianos, evaluated 159 total patients. Among them, 92 individuals presented with pure urothelial carcinoma, while 67 carried a histological subtype defined by a nonurothelial component representing at least 5% of the tumor in the cystectomy specimen. Routine clinical practice utilized the Signatera 16-plex multiplex PCR next-generation sequencing assay to perform tumor-informed circulating tumor DNA assessments.
Aggressive Features and Disease-Free Survival Outcomes
Patients harboring histological subtypes demonstrated more aggressive clinical profiles than those with pure urothelial tumors. Preoperative ctDNA detectability reached 61% in the subtype cohort, compared with 40% in the pure urothelial group. Furthermore, advanced pathological staging of pT2 or greater appeared in 90% of the histological subtype patients, alongside a 39% rate of lymph node involvement.
Following a median follow-up of 21 months for preoperative evaluations and 22 months for postoperative assessments, recurrence or death occurred in dozens of cases.
- Pure urothelial carcinoma with undetectable preoperative ctDNA: 89% disease-free survival
- Pure urothelial carcinoma with detectable preoperative ctDNA: 49% disease-free survival
- Histological subtypes with undetectable preoperative ctDNA: 79% disease-free survival
- Histological subtypes with detectable preoperative ctDNA: 43% disease-free survival
Multivariable adjustment confirmed that detectable preoperative ctDNA remained an independent predictor of recurrence or death, yielding a hazard ratio of 4.07 for pure urothelial carcinoma and 3.99 for histological subtypes. Postoperative assessments showed a similar stratification: patients with detectable postoperative ctDNA faced risks, with 24-month disease-free survival dropping to 30% in pure urothelial cases and 29% in histological subtypes.
Expanding Liquid Biopsy Utility in Upper Tract Urothelial Carcinoma
Beyond the bladder, liquid biopsy applications are transforming management frameworks in adjacent urologic malignancies. Upper tract urothelial carcinoma presents a clinical challenge due to its rarity, accounting for only 5% to 10% of urothelial cancers, and its anatomical resistance to reliable sampling.
While traditional diagnostic modalities like computed tomography urography, cytology, and ureteroscopy remain indispensable for mapping anatomy, they struggle to capture tumor biology. A review highlights that urine-based liquid biopsy platforms—incorporating DNA methylation, mutational, multiplex RNA, copy-number, and protein assays—provide mature tools for noninvasive preoperative triage. Meanwhile, plasma circulating tumor DNA links more closely to biological upstaging, occult muscle-invasive disease, and molecular residual disease surveillance.
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Petros Grivas, via Urotoday
Consolidation Strategies and Next-Generation Testing Horizons
As professional societies prepare for upcoming scientific assemblies, clinical discussions center on integrating systemic therapies such as enfortumab vedotin combined with pembrolizumab alongside biomarker surveillance. Experts previewing the Urotoday meeting note that managing patients with oligometastatic disease who achieve deep responses introduces decisions regarding consolidative surgery, radiation, or selective organ preservation.
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