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Sunday, November 15, 2026

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Urine tumor DNA

Figures are from the cited sources and are not head-to-head comparable. Assay names are labels, not a ranking.

What is MRD?

For clinicians

Minimal residual disease (MRD) is cancer that remains after treatment intended to remove all detectable disease, at a level below conventional imaging or routine pathology. The term comes from hematologic malignancies, where it is measured in bone marrow or blood with established assays and thresholds. In solid tumors, the same idea is usually assessed with circulating tumor DNA (ctDNA) in plasma, or, in urothelial cancer, with urine tumor DNA (utDNA). Many papers now say molecular residual disease for ctDNA- or utDNA-detected disease after curative-intent therapy, to distinguish it from the hematologic usage. A positive MRD test means tumor-derived nucleic acid was detected at that time point and, in multiple bladder-cancer studies, has been associated with a higher risk of residual disease or recurrence. It is not, by itself, radiographic proof of relapse, and it is not a stand-alone indication for a specific drug. A negative test lowers the probability of detectable residual disease in those same studies; it does not prove that every cancer cell is gone. Performance depends on the assay, the time point, the setting, and how residual disease is defined. Figures from different papers should not be used to rank tests.

For patients

After treatment meant to remove all the cancer that doctors can see — surgery, chemotherapy, immunotherapy, radiation, or a combination — scans and cystoscopy can look clear. MRD (minimal residual disease, sometimes called molecular residual disease) means a laboratory test still found traces of cancer that are too small for a scan to show. In bladder and urothelial cancer, that test is often done on a blood sample (circulating tumor DNA, or ctDNA) or on a urine sample (urine tumor DNA, or utDNA). A positive result means cancer DNA was found. In several studies, people with a positive result were more likely to have cancer left behind or to have it come back. It does not automatically mean the cancer is already visible again, and it does not by itself decide the next treatment. A negative result means the test did not find cancer DNA at that time. In several studies that was reassuring, but it does not prove that every last cancer cell is gone. No urine or blood test has replaced cystoscopy or scans as the sole way to watch for bladder cancer. If you have a result to discuss, it should be interpreted with your clinician, in the context of your diagnosis and the specific test that was used.

What urine tumor DNA is

Urine sits against the lining of the bladder (the urothelium) and also contacts the lining of the kidneys and ureters. As tumor and lining cells turn over, fragments of DNA enter the urine. The fraction that comes from the tumor is urine tumor DNA (utDNA), also called urinary tumor DNA or urine ctDNA.

Direct contact with the tumor-bearing lining. Unlike plasma, urine is in physical contact with urothelial tumors. That is the anatomic rationale for a urine test in bladder-intact disease.

Often a higher tumor fraction than plasma in localized disease. Shi et al., Cell 2026, same-day pairs: tumor-derived DNA in 10/10 NMIBC urine vs 0/10 plasma, and 6/6 MIBC urine vs 3/6 plasma (small n; not a commercial head-to-head). Zhang et al., J Urol 2021, PredicineCARE, n=59: urine-versus-tissue sensitivity 86.7%, specificity 99.3%, accuracy 99.1%, closer agreement than plasma. Chauhan et al., NPJ Precis Oncol 2023, n=74: urine multi-omics predicted pCR 'far better than plasma ctDNA was able to.'

Detection of biomarkers including FGFR3 and other actionable alterations. Dudley 2019: median 6 mutations per patient; PLEKHS1 promoter mutations in 46%. Zhang J Urol 2021: FGFR3 alteration and ERBB2 amplification in urine. Zhang CCR 2023: 4 of 20 patients harbored FGFR3 mutants in utDNA. Frequencies differ by cohort and assay and should not be pooled.

Bladder-intact treatment and surveillance. Serial urine testing can be used, in research and in exploratory trial analyses, to look for residual local disease after TURBT, BCG, systemic therapy, or trimodal therapy, and during NMIBC surveillance. See major_studies.

Limits

Field cancerization. Mutations in normal-appearing urothelium can be shed into urine after the visible tumor is gone. A positive result may reflect field changes rather than residual tumor.

Upper-tract contribution. Urine is a composite from bladder, ureters, and renal pelvis. A positive test does not locate the source. UroSEEK was positive in 75% of 56 UTUC patients (Springer 2018). After cystectomy, post-cystectomy studies have generally used plasma ctDNA (Christensen 2019; TOMBOLA 2026).

Lack of standardization. Assays differ in analyte, tumor-informed vs naive design, gene content, positivity calls, and field-mutation handling. No single accepted LOD or shared threshold. Collection and processing are not uniform.

Age-related mutations in people without cancer (clonal cystopoiesis). Shi et al., Cell 2026: putative oncogenic mutations in urine increased with age, to approximately 20% of people beyond 75 years. Most frequent: PLEKHS1 9%, TERT 2.9%, KMT2D 1.4%, FGFR3 0.7%.

Not a treatment decision by itself. Almost every study below is prognostic or exploratory. Prospective utility trials that change treatment on the basis of utDNA and then show improved outcomes are still limited.

Field cancerization

Field cancerization means a region of tissue that still looks normal already carries genetic or epigenetic changes shared with, or ancestral to, a nearby cancer. Eight cited studies are listed under the figure.

Field cancerization and what a urine DNA test can pick up

Before the visible tumor is removedAfter the visible tumor is removedUrineBladder muscleUrineBladder muscleTumorDNA from the tumorDNA from field clones (normal-appearing lining)Normal-appearing urothelium with mutant clones

After the visible tumor is removed, a positive urine DNA result may come from leftover field changes, not only from residual tumor.

Normal-appearing bladder lining can carry mutant clones. Lawson et al., Science 2020, sequenced 2,097 microbiopsies from 20 people. Li et al., Science 2020, described clones that expanded to several square centimeters. Shi et al., Cell 2026, found that in 25 of 51 patients only a subset of the tumor’s mutations were present in adjacent normal tissue, and that oncogenic mutations were present in the urine of about 20% of people without cancer who were older than 75.

  1. Peer-reviewed

    Review of 10 years of molecular studies: the majority showed a monoclonal origin of multifocal urothelial tumors, with a smaller but significant set of findings consistent with oligoclonal or independent tumors, especially in earlier disease.

    Hafner, Knuechel, Stoehr, Hartmann. Int J Cancer 2002.
  2. Peer-reviewed

    Widespread DNA methylation changes in the entire mucosa as the initial field effect; founder ACIN1 mutation in normal mucosa expanded clonally with an additional 21 mutations in progression to carcinoma; nearly identical mutation and copy-number patterns in CIS and carcinoma foci, confirming clonal origins.

    Majewski et al., with Czerniak. Cell Rep 2019;26(8):2241-2256.e4.
  3. Peer-reviewed

    Widespread positive selection in 17 genes; frequent mutations in chromatin-remodeling genes; mutations absent in several major bladder-cancer genes; extensive interindividual variation; APOBEC mutagenesis in 22% of microbiopsies.

    Lawson, Abascal, Coorens et al., with Martincorena, Mitchell, Campbell, Stratton. Science 2020;370(6512):75-82.
  4. Peer-reviewed

    Macroscopic somatic clonal expansions in morphologically normal human urothelium. Aristolochic acid was a major mutagenic driver in that cohort. Mutations widely observed in KMT2D and KDM6A, rarely in TP53, PIK3CA, and FGFR3. Single AA-associated clones expanded to a scale of several square centimeters.

    Li, Du, Chen, Xu, Lin et al. Science 2020;370(6512):82-89.
  5. Peer-reviewed

    Accompanying commentary on mutational selection in normal urothelium.

    Rozen SG. Science 2020.
  6. Peer-reviewed

    Targeted sequencing of normal urothelium and tumor from patients with NMIBC.

    Hayashi, Fujita, Sakai, Adomi et al. Sci Rep 2022.
  7. Peer-reviewed

    In 16 (31%) of 51 previously profiled patients, all tumor mutations were present in adjacent normal tissue (tumor contamination or complete overlap). In 25 (49%), only a subset of tumor mutations were present in adjacent normal, a pattern judged inconsistent with simple contamination and consistent with a field effect. Putative oncogenic mutations in urine of non-cancer controls increased with age to approximately 20% beyond 75 years (clonal cystopoiesis): PLEKHS1 9%, TERT 2.9%, KMT2D 1.4%, FGFR3 0.7%.

    Shi, Liu, Esfahani, Mach et al. Cell 2026;189(4):1024-1038.e9.
  8. Peer-reviewed

    Sex and smoking bias in the selection of somatic mutations in the human bladder, extending the normal-urothelium mutation landscape.

    Calvet et al. Nature 2025.

Why urine tumor DNA can help find biomarkers

A one-minute animated explainer. Numbers shown come from individual cited studies and are not a comparison of commercial tests. This is research context; it does not replace cystoscopy.

Why urine tumor DNA can help find biomarkers in bladder cancer

0-6s

Urine

Urine touches the lining of the bladder.

CaptionThe bladder's inner lining is in direct contact with urine. If a tumor is there, it can shed DNA into the urine.

Scene 1 of 8. About 60 seconds.

Featured · Source type not stated

Liu et al., Nature Medicine 2026

Urine cell-free RNA for bladder cancer detection and treatment response prediction.

Nat Med. Published 2 October 2026. Open access on the Nature page.

PMID 42827132
  • 95% sensitivity at 90% specificity for detecting localized bladder cancer.
  • Outperformed urine tumor DNA analysis and was unaffected by field-effect mutations.
  • Sensitively detected MRD and distinguished complete molecular responses after surgery from those after BCG.
  • Pretreatment urine from BCG complete responders enriched for T-cell and other immune signatures; nonresponders showed higher proliferation-related gene expression.
  • In pretreatment urine from 114 patients, a biomarker predicting BCG versus chemotherapy response had AUC 0.93 and was strongly associated with recurrence risk.
  • Authors state prospective studies are needed to assess clinical utility.

Conference abstract. Listed separately from the Nature Medicine paper.

Urine cell-free RNA analysis for bladder cancer detection and monitoring.

  • Locked model: 95% sensitivity at 90% specificity; independent validation 94% sensitivity and 88% specificity; LOD 0.05%.
  • Sensitivity: 86% low-grade Ta, 97% high-grade Ta, 100% high-grade CIS, 100% high-grade tumors greater than T1.
  • 37 post-BCG samples: residual BLCA cfRNA associated with recurrence, HR 42.27, log-rank P < 0.0001.
  • Grade model AUC 0.85; NMIBC vs MIBC AUC 0.82.
Liu, Shi, Nesselbush, Phillips et al., including Alizadeh, Liao, Diehn. Cancer Res 2025;85(8_Suppl_1):Abstract 3773. AACR 2025.

Alan Tan and Predicine

A search found 0 peer-reviewed PubMed papers with Alan Tan as an author on Predicine urine or plasma bladder results. The two items below are conference abstracts only.

Conference abstract

Comparison of clinical outcomes of bladder preservation and surgery in a real-world study of patients with muscle invasive urothelial carcinoma using urine and plasma based MRD (minimal residual disease) assays.

J Clin Oncol. 2024;42(16_suppl):e16580. Published online 29 May 2024. Conference abstract; no full text.

  • 94 urine and 253 plasma MRD tests, success rates 'over 90%'.
  • Median follow-up 6.5 months.
  • Tumor fraction and kinetics from urine MRD 'in high concordance' with blood MRD at matching time points.
  • Allele-frequency changes 'matched with patient treatment responses and progression events in most cases.'
  • Increases in mutations and tumor fraction observed in patients with progressive disease.
  • Patients receiving definitive therapy had 'good disease-free survival time (longest >2 years),' and 'there is no significant difference between bladder preservation or surgery-based intervention.'
  • Authors state the number of cases was limited and further follow-up is needed.

Not published in the abstract: Hazard ratios, exact concordance percentages, NMIBC/MIBC/UTUC breakdown, and a defined statistical test for the 'no significant difference' claim.

A free public poster or webcast was not found. The citable record is the abstract page.

Conference abstract

Comprehensive bladder cancer molecular profiling and monitoring based on mutational, epigenomic, and expression data from real-world patients.

J Clin Oncol. 2025;43(5_suppl):860. Published online 18 Feb 2025. Conference abstract; no full text.

  • Integrated assay 'generated significantly more comprehensive data compared to mutational panels alone.'
  • 'Strong correlation was observed for some bladder cancer biomarker genes such as TERT and TP53' between DNA methylation and RNA expression.
  • An AI model trained on the treatment decision (bladder preservation versus surgery), clinical features, and molecular data 'accurately matches the physician's choices over 90% of the validation cases.'
  • Authors say sample size is limited and further validation in larger independent cohorts is needed.

A free public poster or webcast was not found. The citable record is the abstract page.

Related Predicine papers by other authors

These do not list Alan Tan as an author.

  • Peer-reviewed · Not Alan Tan

    NOT Alan Tan. PredicineCARE, n=59 tissue/urine pairs. Urine-vs-tissue sensitivity 86.7%, specificity 99.3%, PPV 67.2%, NPV 99.8%, accuracy 99.1%. FGFR3 and ERBB2 amplification in urine.

    Zhang, Zang, Xie et al. (Jia, Du co-authors). J Urol 2021;206(4):873-884.
  • Peer-reviewed · Not Alan Tan

    NOT Alan Tan. n=20 neoadjuvant toripalimab, tissue-agnostic urine MRD (Predicine co-authors). pCR 40% (8/20). Authors report 3 molecular MRD-negative exceptional responders, 7 other utDNA responders, 4 FGFR3 mutants, and interpret that 12/20 (60%) 'could have postponed or avoided' RC — authors' interpretation, not a randomized result.

    Zhang, Zang, Jin et al. Clin Cancer Res 2023;29(20):4040-4046.
  • Conference abstract · Not Alan Tan

    NOT Alan Tan (Ruiyun Zhang, Di Jin, Jingyu Zang et al., Renji / Predicine). n=100 MIBC TMT candidates, PredicineCARE. Baseline urine: TP53 38%, TERT 30%, FGFR3 19%, ARID1A 16%, PIK3CA 14%. TF reduction in urine in 38 and blood in 25, overlap 13; 4 with no detectable TF at last follow-up. Conference abstract.

    J Clin Oncol 2024;42(16_suppl):e16602.

  • Peer-reviewed · Not Alan Tan

    NOT Alan Tan. Exploratory ctDNA and utDNA using PredicineCARE in a DV + toripalimab + radiotherapy organ-sparing proof-of-concept study.

  • Peer-reviewed · Not Alan Tan

    NOT Alan Tan. Plasma PredicineATLAS in POLARIS-03 metastatic urothelial carcinoma. Plasma, not urine.

  • Peer-reviewed · Not Alan Tan

    NOT Alan Tan. Plasma Predicine work to identify muscle-invasive and non-organ-confined UTUC. Not urine MRD.

Major studies

23 catalog entries. Galsky is a co-author of the NIAGARA NEJM paper and first author of the bladder-sparing papers. He is not an author of the SunRISe-4 JCO paper. Plasma studies are labeled plasma, not utDNA. SunRISe-1 response rates are not shown. SunRISe-3 utDNA results are not published.

  1. Peer-reviewed

    clinical trial (not utDNA; context)

    Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer.

    Powles T, Catto JWF, Galsky MD, et al., including van der Heijden MS, NIAGARA Investigators.

    N Engl J Med 2024;391(19):1773-1786.

    n: 1063 (533 durvalumab, 530 comparison)

    Phase 3, cisplatin-eligible MIBC

    Assay: n/a (clinical end points)

    • 24-month EFS 67.8% vs 59.8%, HR 0.68 (0.56-0.82), P<0.001.
    • 24-month OS 82.2% vs 75.2%, HR 0.75 (0.59-0.93), P=0.01.

    co-author

  2. Conference abstract

    plasma ctDNA (not utDNA)

    Circulating tumor DNA (ctDNA) in patients with MIBC who received perioperative durvalumab in NIAGARA.

    J Clin Oncol 2025;43(16_suppl):4503.

    n: BEP 462 of 1063 (237 D, 225 C)

    Exploratory plasma ctDNA in NIAGARA

    Assay: Signatera, tumor-informed (Natera)

    • Baseline ctDNA+ 57% (260/460), pre-RC 22% (94/422).
    • Clearance baseline to pre-RC: 41% durvalumab vs 31% comparator.
    • Non-pCR 97% (86/89) if pre-RC ctDNA+.
    • Post-RC ctDNA+ 9% (31/345).
    • EFS benefit of durvalumab reported in both baseline ctDNA+ and ctDNA- groups.

  3. Conference abstract

    utDNA and plasma ctDNA

    Urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) in patients with MIBC who received perioperative durvalumab in NIAGARA.

    J Clin Oncol 2026;44(7_suppl):636. ASCO GU 2026. Conference abstract; not a full paper.

    n: BEP 265 of 1063 (25%; 134 D, 131 C); utDNA at BL n=205, pre-RC n=183

    Exploratory utDNA + ctDNA in NIAGARA, cisplatin-eligible MIBC, pre-cystectomy

    Assay: Personalized Signatera (Natera), same framework as the plasma test

    • Lower baseline utDNA associated with longer EFS (low vs high HR 0.65, 95% CI 0.40-1.04).
    • utDNA+ rate 85% at baseline, 55% pre-RC.
    • utDNA clearance associated with longer EFS (HR 0.24, 95% CI 0.09-0.62); clearance 39% vs 27% (12 points higher with durvalumab).
    • Pre-RC utDNA-: pCR 72% (55/76) vs 18% (17/96) if utDNA+.
    • utDNA+ correlated with noninvasive residual disease (<T2N0M0); ctDNA+ with invasive disease or N+/M+.
    • 24-month EFS: dual-negative 90% (83-97), utDNA+ only 75% (65-87), dual-positive 55% (41-75).

    Conference abstract, exploratory, 25% of ITT. Full paper not found in PubMed.

    UroToday interview, Michiel van der Heijden. Interview commentary (e.g. plasma thresholds used for urine) is not a paper result.

  4. Peer-reviewed

    utDNA and plasma ctDNA MRD (exploratory) plus clinical end points

    Gemcitabine Intravesical System Plus Cetrelimab or Cetrelimab Alone as Neoadjuvant Therapy in Muscle-Invasive Bladder Cancer: SunRISe-4 Primary Analysis and Biomarker Results.

    Necchi A, Guerrero-Ramos F, Crispen PL, Herrera-Imbroda B, Garje R, Szabados B, Peyton CC, Pradere B, Ku JH, Shore N, Bogemann M, Preston MA, Xylinas E, Sanchez de Llano C, Gong C, Hasan M, Urtishak K, Battaglia S, Stitou H, Bhanvadia S, Sweiti H, Psutka SP (22 authors on PubMed; Galsky MD is not on this list).

    J Clin Oncol 2026;44(7):586-597. Published 3 December 2025.

    n: 159 treated; 88 cohort 1 and 46 cohort 2 underwent RC; utDNA available 67 at baseline, 65 at week 12

    Phase 2, cisplatin-ineligible or -refusing cT2-T4a N0M0 MIBC planned for RC; 5:3 randomization, cohort 1 TAR-200 + cetrelimab, cohort 2 cetrelimab alone. Data cutoff 9 May 2025.

    Assay: utDNA and ctDNA MRD; vendor and gene content not named in the abstract (vendor and gene content are not named in the abstract).

    • pCR, pOR (<=ypT1N0), 1-year RFS: 38%, 53%, 77% in cohort 1 vs 28%, 44%, 64% in cohort 2.
    • Baseline utDNA+ 55/67 (82.1%); week 12 utDNA+ 34/65 (52.3%).
    • Week-12 utDNA- and clearance correlated with pCR (P<10^-5 and P<10^-3 in abstract; Fisher P=5.4e-6 for week-12 status in results text).
    • 22/27 (81.5%) who achieved pCR were utDNA- at week 12 vs 7/33 (21.2%) who did not. ROC 0.80 (0.70-0.90); NPV 0.81.
    • Clearance in 14/30 (46.7%) with available data (7/18 C1, 7/12 C2). 12/15 (80.0%) baseline+ with pCR had clearance vs 2/15 (13.3%) without pCR.
    • ctDNA- at baseline and week 12 associated with longer RFS (P=0.04 and 0.01).
    • Authors: utDNA and ctDNA support further investigation as biomarkers for residual local and nonlocal disease, respectively.

    Not on the PubMed author list of this JCO paper. Galsky's own utDNA work is the HCRN GU16-257 PNAS 2026 paper.

  5. Peer-reviewed

    clinical (utDNA not in main abstract)

    TAR-200 for BCG-Unresponsive High-Risk NMIBC: Results From the Phase IIb SunRISe-1 Study.

    Daneshmand S, Van der Heijden MS, Jacob JM, et al., including Necchi A.

    J Clin Oncol 2025;43(33):3578-3588.

    • The main paper’s abstract does not report utDNA. Complete numeric utDNA results from ESMO 2025 abstract 3088P were not extracted from the primary abstract, so those rates are not shown.

    ESMO 2025 abstract 3088P (Ann Oncol, S0923-7534(25)04622-8) and a J&J Medical Connect congress PDF address molecular markers including baseline urinary tumor DNA MRD. Complete numeric utDNA results were not independently extracted from the primary abstract. Rates from that abstract are not included.

  6. Trial in progress

    utDNA results not published

    SunRISe-3: TAR-200 plus cetrelimab or TAR-200 versus BCG in BCG-naive high-risk NMIBC (trial in progress).

    e.g. ESMO 2023 2407TiP. No published utDNA results found.

    utDNA results: not published.

  7. Peer-reviewed

    clinical outcomes in FGFR3/2-altered NMIBC; utDNA/urine FGFR monitoring not in final abstract

    Erdafitinib in Patients with High- and Intermediate-risk Non-muscle-invasive Bladder Cancer: Final Analysis of THOR-2 Study.

    Daneshmand S, Zaucha R, Catto JWF, Tran B, Master V, Lotan Y, et al., including Maranchie JK.

    Eur Urol 2026;89(2):165-173.

    • Cohort 1 (HR papillary, prior BCG), n=73, 2:1 erdafitinib vs intravesical chemo: median RFS NR (28.6 mo-NE) vs 11.6 mo, HR 0.28 (0.13-0.61), nominal P=0.0007.
    • Cohort 2 (CIS +/- papillary), n=16: CR 94% at 8 weeks, 81% at 32 weeks; mDoR 23.3 months.
    • Cohort 3 (IR), n=18: CR 89%.

    A urine FGFR or utDNA monitoring analysis is not described in the final-paper abstract. How FGFR3/2 alterations were ascertained (tissue vs urine) is not stated in that abstract.

  8. Peer-reviewed

    plasma tumor-informed ctDNA (NOT utDNA)

    ctDNA-guided immunotherapy following radical cystectomy for muscle-invasive bladder cancer: results from the TOMBOLA trial.

    Dyrskjot L, Birkenkamp-Demtroder K, Nordentoft I, et al., including Jensen JB.

    Ann Oncol 2026;37(5):712-724.

    n: 192 enrolled, 178 assessable, median FU 34 months

    Danish multicenter, open-label, single-arm phase 2. MIBC after NAC and RC. ctDNA+ started atezolizumab up to 1 year; ctDNA- received IO only if imaging showed metastases.

    Assay: Serial tumor-informed plasma ctDNA (not utDNA)

    • 104 (58%) ctDNA+ within 2 years after RC, 63% of those within 4 months.
    • Median lead time ctDNA to imaging-confirmed recurrence: 90 days (range -61 to 961).
    • 60% (50/84) of ctDNA+ patients who completed atezo with scans/ctDNA for the primary end point achieved complete molecular and radiographic response.
    • 1-year RFS 97% if ctDNA- vs 76% if ctDNA+.

  9. Peer-reviewed

    plasma ctDNA (NOT utDNA)

    Early Detection of Metastatic Relapse and Monitoring of Therapeutic Efficacy by Ultra-Deep Sequencing of Plasma Cell-Free DNA in Patients With Urothelial Bladder Carcinoma.

    Christensen E, Birkenkamp-Demtroder K, Sethi H, et al., including Dyrskjot L.

    J Clin Oncol 2019;37(18):1547-1557.

    n: 68 patients, 656 plasma samples

    Assay: Tumor-informed ultra-deep sequencing (median 105,000x)

    • ctDNA at diagnosis HR 29.1, P=0.001.
    • After cystectomy, ctDNA identified metastatic relapse with 100% sensitivity and 98% specificity; median lead time 96 days.
    • ctDNA dynamics during chemo associated with recurrence (P=0.023); pathologic downstaging was not.

  10. Peer-reviewed

    utDNA

    Urine tumor DNA detection of minimal residual disease in muscle-invasive bladder cancer treated with curative-intent radical cystectomy: A cohort study.

    Chauhan PS, Chen K, Babbra RK, et al., including Smith ZL, Arora VK, Chaudhuri AA.

    PLoS Med 2021;18(8):e1003732.

    n: 42 localized bladder cancer (32 MIBC, 19 of those with NAC) and 15 healthy adults

    Urine on the day of curative-intent RC

    Assay: uCAPP-Seq, tumor-naive (Diehn-group method; WashU / Chaudhuri lab, not a Diehn-lab paper)

    • Median utDNA 0% healthy vs 2.4% patients; 4.3% if residual disease (n=16) vs 0% if pCR (n=26), P=0.002.
    • utDNA MRD vs absence of pCR: sensitivity 81%, specificity 81%; LOO accuracy 81% (P=0.007).
    • PFS HR 7.4 (1.4-38.9), P=0.02.
    • Mutation concordance with tumor in 5 patients: 85%.

  11. Peer-reviewed

    utDNA multi-omics

    Urine cell-free DNA multi-omics to detect MRD and predict survival in bladder cancer patients.

    Chauhan PS, Shiang A, Alahi I, et al., including Chaudhuri AA.

    NPJ Precis Oncol 2023;7(1):6.

    n: 74

    Localized bladder cancer

    Assay: ULP-WGS plus uCAPP-Seq

    • Random-forest LOOCV 87% sensitive for residual disease vs surgical pathology.
    • PFS HR 3.00, P=0.01; OS HR 4.81, P=0.009.
    • Urine metrics predicted pCR 'far better than plasma ctDNA was able to.'

  12. Peer-reviewed

    clinical bladder-sparing (context for utDNA follow-up)

    Gemcitabine and cisplatin plus nivolumab as organ-sparing treatment for muscle-invasive bladder cancer: a phase 2 trial.

    Galsky MD, Daneshmand S, Izadmehr S, et al.

    Nat Med 2023;29(11):2825-2834.

    n: 76

    • cCR 43% (33/76, 95% CI 32-55%); 32 of 33 with cCR opted to forgo immediate cystectomy; PPV of cCR 0.97 (0.91-1).

  13. Peer-reviewed

    plasma ctDNA and utDNA

    Monitoring of plasma and urine tumor-derived DNA to inform bladder-sparing approaches for patients with muscle-invasive bladder cancer.

    Galsky MD, Izadmehr S, Yu M, Curtis SD, Douville C, et al., including Bettegowda, Kinzler, Papadopoulos, Vogelstein, Wang Y.

    Proc Natl Acad Sci USA 2026;123(8):e2533449123.

    Exploratory liquid biopsy in the gem/cis/nivo bladder-sparing trial; tumor-informed academic assay; authors note relatively small sample.

    Assay: Tumor-informed academic ctDNA and utDNA assay

    • 3-year bladder-intact survival among cCR after four rounds of systemic therapy: 69%.
    • Metastatic risk if pretreatment ctDNA detectable vs undetectable: HR 4.68 (1.10-43.35), P=0.036.
    • Only 4.5% (1 of 22) with undetectable baseline ctDNA developed metastatic disease.
    • utDNA more sensitive than plasma ctDNA for residual disease in the bladder.
    • Detectable utDNA in patients with cCR associated with shorter bladder-intact survival, HR 6.47 (1.34-31.31), P=0.008.

    first author — this is the Galsky utDNA study

  14. Peer-reviewed

    tissue/immune biomarkers; utDNA not in abstract

    Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial.

    Powles T, Kockx M, Rodriguez-Vida A, et al.

    Nat Med 2019.

    n: 95

    • pCR 31% (95% CI 21-41%). Biomarkers are tissue and immune contexture; utDNA is not reported in the abstract.

  15. Not fully verified

    utDNA not verified

    ABACUS-2

    ESMO 2023 2363MO: neoadjuvant atezolizumab in non-urothelial MIBC. ASCO GU 2026 abstract 832: biomarker analysis of neoadjuvant atezolizumab in UTUC from ABACUS-2. A PubMed-indexed paper and a verified utDNA numeric analysis were not found.

  16. Peer-reviewed

    urine DNA (mutations + aneuploidy)

    Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy.

    Springer SU, Chen CH, Rodriguez Pena MDC, et al., including Papadopoulos, Kinzler, Vogelstein, Netto.

    eLife 2018;7:e32143.

    n: 570 at risk for BC; 56 UTUC; surveillance subset

    Assay: UroSEEK: 11 genes plus copy-number changes on 39 chromosome arms

    • Positive in 83% of those who developed BC; combined with cytology, 95%.
    • UTUC: 75% of 56 positive (79% of non-invasive tumors).
    • Surveillance: genetic abnormalities in 68% of urines from patients with clinical recurrence.
    • Low-grade BC: UroSEEK 67%, cytology 0%.

  17. Peer-reviewed

    urine DNA methylation

    Urine DNA methylation assay enables early detection and recurrence monitoring for bladder cancer.

    Chen X, Zhang J, Ruan W, et al.

    J Clin Invest 2020;130(12):6278-6289. utMeMA.

    n: Model built in 313; prospective multicenter validation 175

    • 2-marker model: accuracy 86.7%, sensitivity 90.0%, specificity 83.1%.
    • Early-stage Ta and low-grade: sensitivity 64.5% vs cytology 11.8% and FISH 15.8%.

  18. Peer-reviewed

    multitarget urine tumor DNA (mutations + methylation)

    Clinical effectiveness of a multitarget urine DNA test for urothelial carcinoma detection: a double-blinded, multicenter, prospective trial.

    Wu J, Lin Y, Yang K, et al.

    Mol Cancer 2024;23(1):57. UI-Seek.

    n: Development 382; prospective validation 947 (ChiCTR2300076543)

    Assay: FGFR3 and TERT mutations plus ONECUT2 and VIM methylation

    • Sensitivity 91.37%, specificity 95.09%.
    • 75.81% for low-grade Ta; >93% for high-grade Ta and higher stages; >90% for both bladder and upper-tract tumors.
    • Post-surgery UC-score decreased in 97.7% (43/44).

  19. Peer-reviewed

    utDNA methylation (BladMetrix)

    Distinct longitudinal patterns of urine tumor DNA in patients undergoing surveillance for bladder cancer.

    Vedeld HM, et al.

    Mol Oncol 2024;18(11):2684-2695.

    n: 47 patients, 2-year surveillance

    • Detected 21/23 recurrences (91%): 5/5 T1, T2, and CIS (100%) and 10/12 Ta (83%); <1% false-negative tests.
    • Authors estimate a potential 55% reduction in cystoscopies, benefiting 79% of patients (estimate from the paper, not a randomized result).
    • 11/23 recurrences (48%) detected earlier with utDNA than cystoscopy.
    • Residual-utDNA patterns interpreted as MRD in 6% and field effect in 15%.

  20. Peer-reviewed

    urinary tumor-derived DNA plus multi-omics

    Elevated T-cell Exhaustion and Urinary Tumor DNA Levels Are Associated with BCG Failure in Patients with NMIBC.

    Strandgaard T, Lindskrog SV, Nordentoft I, Christensen E, Birkenkamp-Demtroder K, et al., including Jensen JB, Dyrskjot L.

    Eur Urol 2022;82(6):646-656.

    n: 156 BCG-treated NMIBC; urine tdDNA n=187 samples

    • Absence of post-BCG tdDNA clearance identified patients at high risk of recurrence (P=0.018).
    • Post-BCG HG recurrence associated with T-cell exhaustion (P=0.002).

  21. Peer-reviewed

    utDNA (UroAmp)

    Urine Tumor DNA to Stratify the Risk of Recurrence in Patients Treated with Atezolizumab for BCG-unresponsive NMIBC.

    St-Laurent MP, Singh P, McConkey DJ, et al., including Lerner SP, Black PC.

    Eur Urol 2025;88(5):430-434. SWOG S1605.

    n: UroAmp at baseline n=89 and 3 months n=77

    Assay: UroAmp

    • CR at 6 months: 13% of UroAmp+ vs 71% of UroAmp- at baseline (P<0.001).
    • 18-month EFS 23% vs 51% (HR 2.8, P<0.001).
    • Among 51 with no clinical evidence of disease at 3 months: 18-month EFS 38% if UroAmp+ vs 86% if negative (HR 3.5, P=0.01).

  22. Peer-reviewed

    utDNA

    Postinduction Urine Tumor DNA Is Predictive for Response to Maintenance Intravesical Therapy in NMIBC.

    Lotan Y, Korman H, Gadzinski A, et al.

    Eur Urol Oncol 2026. INSITE, observational.

    n: 140 evaluable, 47% received maintenance

    • utDNA-: no significant RFS benefit from maintenance (HR 1.35, 0.50-3.64, P=0.6); 24-month RFS 88% with or without maintenance.
    • utDNA+: maintenance associated with better RFS (HR 0.22, 0.09-0.52, P<0.001); 24-month RFS 68% with maintenance vs 16% without.
    • Observational; not a randomized test of utDNA-guided maintenance.

  23. Bibliographic catalog

    Additional verified 2025-2026 utDNA citations

How MRD tests differ