What the studies show

Must-know papers

Urine tumor DNA studies

From the utDNA catalog. Plasma ctDNA studies are labeled plasma. Conference abstracts stay labeled as abstracts. These figures are not a ranking.

1. Peer-reviewed

   Detection and Surveillance of Bladder Cancer Using Urine Tumor DNA.

   Dudley JC, Schroers-Martin J, Lazzareschi DV, Shi WY, Chen SB, Esfahani MS, Trivedi D, Chabon JJ, Chaudhuri AA, et al.; Alizadeh AA and Diehn M senior.

   Cancer Discov 2019.

   n: 67 healthy adults and 118 patients with early-stage bladder cancer

   Pretreatment or surveillance, early-stage BLCA

   Assay: uCAPP-Seq (utDNA CAPP-Seq), targeted high-throughput sequencing

   • Median 6 mutations per patient; PLEKHS1 promoter mutations in 46%.
   • Pretreatment detection 93% tumor-informed, 84% tumor-naive, 96% to 100% specificity.
   • Surveillance: utDNA detected in 91% of patients who ultimately recurred; preceded clinical progression in 92% (median lead time 2.7 months in the full text).
   • Outperformed UroVysion (P=0.02) and cytology and cystoscopy combined (P<=0.006); detected 100% of cytology-positive cases and 82% that cytology missed (abstract).
   • Surveillance subset in full text: tumor-naive profiling detected 100% of recurrent cases with positive cytology (n=14) and 73.9% with negative cytology (n=23).

2. Peer-reviewed

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

   Liu KJ, Shi WY, Nesselbush MC, Phillips NA, Mach KE, et al.; Alizadeh AA, Liao JC, and Diehn M senior.

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

   n: 683 urine samples from patients with cancer and controls

   Detection, MRD, and BCG-versus-chemotherapy response prediction in bladder cancer; also transcripts from prostate and kidney cancers noted.

   Assay: uRARE-seq (urine random priming and affinity capture of cell-free RNA fragments for enrichment analysis by sequencing)

   • 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.

3. Peer-reviewed

   Field-effect-informed urine liquid biopsy for bladder cancer.

   Shi WY, Liu KJ, Esfahani MS, Mach KE et al. Cell 2026;189(4):1024-1038.e9.

   n: 261 serial specimens from 61 NMIBC patients (validation); plus training and control analyses described in field_cancerization

   Intermediate- or high-risk NMIBC, TURBT and adjuvant BCG

   Assay: Field-effect-informed (RePhyNERX-enhanced) uCAPP-Seq, tumor-informed

4. 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

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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+.

11. 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.

12. 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%.

13. 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.'

14. 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).

15. 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

16. 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.

17. 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%.

18. 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%.

19. 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).

20. 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%.

21. 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).

22. 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).

23. 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.

24. Bibliographic catalog

    Additional verified 2025-2026 utDNA citations

    • Bahlburg et al. J Urol 2026. utDNA in high-risk NMIBC receiving therapy.
    • Huang et al. JCO Precis Oncol 2026. Post-resection urinary tumor DNA in NMIBC.
    • Wu et al. MedComm 2026. Early detection and recurrence monitoring in NMIBC.
    • Cancer Sci 2026. utDNA to identify candidates for repeat TURBT. n=161, residual tumor 35%; sensitivity 80.7%, specificity 96.2%, accuracy 90.7%.
    • 2026 longitudinal UTUC utDNA paper.
    • Li, Linscott, Murthy, Rose et al. medRxiv. Label as preprint, not a journal article.Preprint, not a journal article

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