Molecular or measurable residual disease, including circulating tumor DNA.
A JAMA Oncology analysis published online August 13, 2026, of 1,026 plasma samples from 159 patients in the c-TRAK TN surveillance cohort found that tissue-free ctDNA detection was associated with recurrence (HR 27.2; 95% CI 13.7 to 54.2), and median lead time to recurrence was 7.6 months with the tissue-free assay versus 7.1 months with a multivariant tumor-informed assay.
JAMA Oncology
At ESMO 2026, the PROMPT matched tissue-and-plasma series of 301 patients with metastatic castration-resistant prostate cancer reported that plasma ctDNA detected 50 of 61 patients with a BRCA1/2 or other HRR mutation and added 4 patients beyond tissue sequencing, with matched leukocyte DNA used to separate clonal hematopoiesis.
UroToday
On May 15, 2026, the FDA approved atezolizumab and atezolizumab/hyaluronidase as adjuvant treatment for adults with muscle-invasive bladder cancer after cystectomy who have ctDNA molecular residual disease on an FDA-authorized test, and approved Signatera CDx to select those patients; in IMvigor011 median disease-free survival was 9.9 versus 4.8 months (HR 0.64) and median overall survival was 32.8 versus 21.1 months (HR 0.59).
U.S. FDA
A Cell paper published online November 7, 2025, applied a whole-genome tumor-informed ctDNA assay to 2,994 plasma samples from 431 patients with non-small cell lung cancer in TRACERx and reported that detection below 80 parts per million, before and after surgery, was prognostic, and that patients who cleared ctDNA during adjuvant therapy had better outcomes.
Cell
On January 21, 2026, the FDA released draft guidance on using minimal residual disease and complete response in multiple myeloma to support accelerated approval, defining the MRD endpoint as bone-marrow negativity by flow cytometry or sequencing in patients who have achieved complete response or stringent complete response, and noting that the April 12, 2024 ODAC unanimously accepted MRD as an accelerated-approval endpoint.
Federal Register
In the phase 2/3 DYNAMIC-III trial published in Nature Medicine on October 20, 2025, 702 of 968 evaluable patients with stage III colon cancer were ctDNA-negative 5 to 6 weeks after surgery; 3-year recurrence-free survival was 87% if ctDNA-negative and 49% if ctDNA-positive, de-escalation in the ctDNA-negative group did not meet non-inferiority (85.3% versus 88.1%), and escalation in the ctDNA-positive group did not improve 2-year recurrence-free survival (51% versus 61%).
Nature Medicine
In the phase 3 IMvigor011 trial published in NEJM, 250 of 761 monitored patients with muscle-invasive bladder cancer tested ctDNA-positive after cystectomy and were randomized to atezolizumab or placebo, with median disease-free survival of 9.9 versus 4.8 months (HR 0.64) and median overall survival of 32.8 versus 21.1 months (HR 0.59); persistently ctDNA-negative patients were not treated on study and had a 95% disease-free survival at 1 year.
New England Journal of Medicine
ClinicalTrials.gov lists the observational TiMBER study (NCT07726602), led by OHSU, as recruiting from a June 29, 2026 start date to test whether Labcorp Plasma Detect ctDNA corresponds with recurrence after curative-intent treatment for muscle-invasive urothelial carcinoma.
ClinicalTrials.gov
In a 66-patient retrospective series presented at ASCO GU 2026, baseline Signatera ctDNA positivity before curative-intent treatment for urothelial carcinoma was associated with shorter recurrence-free survival (HR 5.15; 95% CI 1.41 to 18.78).
Journal of Clinical Oncology
An ASCO GU 2026 proof-of-concept series of 33 ctDNA samples from 21 patients with germ cell tumors, most of them marker-negative, reported 100% concordance between ctDNA detection and radiologic or pathologic disease status across the treatment phases assessed.
Journal of Clinical Oncology
Among 64 patients with ctDNA drawn before primary retroperitoneal lymph node dissection, an ASCO GU 2026 analysis reported sensitivity of 88% and specificity of 85% for germ cell tumor in the non-seminoma subgroup of 37 patients; seminoma specificity could not be estimated because every seminoma specimen contained tumor.
Journal of Clinical Oncology
An ASCO GU 2026 retrospective series of patients with testicular cancer who had at least one tumor-informed ctDNA result reported that, in that chart review, ctDNA was more sensitive and specific than serum tumor markers and imaging for residual disease and recurrence.
Journal of Clinical Oncology
In a biomarker analysis of the phase 2 COMRADE trial presented at ASCO GU 2026, undetectable ctDNA at cycle 2 day 1 was associated with longer radiographic progression-free survival than detectable ctDNA (median 9.9 versus 2.7 months; HR 0.47) among 94 analyzed patients with bone-dominant metastatic castration-resistant prostate cancer.
UroToday
A multicenter series of 77 patients with stage I to IV renal cell carcinoma, published in JCO Oncology Advances on January 21, 2026, found that Signatera ctDNA positivity in the molecular-residual-disease window was associated with inferior recurrence-free survival in the landmark analysis (HR 18; 95% CI 4.9 to 67).
JCO Oncology Advances
A Journal for ImmunoTherapy of Cancer analysis published July 11, 2025, of adjuvant nivolumab with or without ipilimumab in resected stage III or IV melanoma found tumor-informed ctDNA at baseline in 16.2% of tested patients, and ctDNA positivity at baseline or on treatment was associated with recurrence (HR 1.97; 95% CI 1.57 to 2.46).
Journal for ImmunoTherapy of Cancer
In the January 13, 2025 Nature Medicine TRACERx analysis, lung adenocarcinomas with preoperative ctDNA detected below 80 parts per million still had worse overall survival than ctDNA-negative adenocarcinomas (HR 12.33; 95% CI 1.63 to 93.35).
Nature Medicine
A Nature Medicine paper published January 13, 2025, tested preoperative plasma from 171 TRACERx patients and detected ctDNA in 76 of 94 lung adenocarcinomas (81%), including 16 of 28 with stage I adenocarcinoma, and in 77 of 77 non-adenocarcinoma non-small cell lung cancers.
Nature Medicine
In the phase 3 ALTAIR trial published in Nature Medicine on June 8, 2026, 243 patients with resected colorectal cancer who became tumor-informed ctDNA-positive without radiographic disease were randomized to trifluridine/tipiracil or placebo; median disease-free survival was 9.30 versus 5.55 months (HR 0.79; P = 0.107), so the primary endpoint was not met.
Nature Medicine
ClinicalTrials.gov lists NCT07401316, a diagnostic study led by Indiana University with Natera, as recruiting from a June 3, 2026 start date to measure the positive predictive value of ctDNA in high-risk stage I, stage II, and stage III germ cell tumors.
ClinicalTrials.gov
In 110 patients with advanced urothelial carcinoma treated with enfortumab vedotin with or without pembrolizumab, an ASCO 2026 analysis of serial Signatera testing associated ctDNA positivity after 12 weeks with worse progression-free survival (HR 36.8) and overall survival (HR 17.7).
Journal of Clinical Oncology
An ASCO 2026 retrospective cohort of 72 patients with high-grade epithelial ovarian cancer, 69 of whom were in clinical remission, found ctDNA positivity in 30 and second-look laparoscopy positivity in 33; on multivariable analysis ctDNA positivity predicted shorter progression-free survival (HR 4.35; 95% CI 2.17 to 8.72).
Journal of Clinical Oncology
A preliminary ASCO GU 2026 report from MONSTAR-SCREEN-3, with results available for 16 of 30 enrolled patients with resectable renal cell carcinoma, found baseline ctDNA in 16 of 16 evaluable patients using a tumor-informed whole-genome assay, including 9 of 16 below 100 parts per million.
Journal of Clinical Oncology
The MolDX billing article A58434, in the revision effective January 1, 2026, lists Signatera for progression, recurrence, or relapse testing in muscle-invasive bladder cancer.
CMS MolDX
The MolDX billing article A58434, in the revision effective January 1, 2026, lists Signatera among the assays covered for progression, recurrence, or relapse testing in ovarian cancer.
CMS MolDX
The MolDX billing article A58434, in the revision effective January 1, 2026, lists Signatera for neoadjuvant breast cancer and lists NeXT Personal, Pathlight, RaDaR, and Signatera for recurrence or relapse testing in advanced breast cancer.
CMS MolDX
The MolDX billing article A58434, in the revision effective January 1, 2026, lists Signatera for the diagnosis of recurrence or relapse in patients with a personal history of non-small cell lung cancer.
CMS MolDX
The MolDX billing article A58434, in the revision effective January 1, 2026, lists Signatera, Guardant Reveal, and Oncodetect for the diagnosis of progression, recurrence, or relapse in advanced colorectal cancer.
CMS MolDX
The MolDX billing article A58434, in the revision effective January 1, 2026, lists HPV-negative head and neck squamous cell carcinoma among covered indications for recurrence testing with RaDaR, and lists HPV-driven oropharyngeal squamous cell cancer among covered indications for NavDx.
CMS MolDX
The MolDX billing article A58434, in the revision effective January 1, 2026, lists Signatera for monitoring response to immune-checkpoint inhibitor therapy in advanced solid tumors and Guardant Response for inoperable or metastatic solid tumors.
CMS MolDX
In the same DYNAMIC-III analysis published in Nature Medicine on October 20, 2025, patients with stage III colon cancer whose ctDNA stayed positive after treatment had a 3-year recurrence-free survival of 14%, compared with 79% among patients who cleared ctDNA.
Nature Medicine
ClinicalTrials.gov lists ADAPT-MRD (NCT06966440) as a recruiting randomized trial that started June 1, 2025, assigning patients after resection of pancreatic cancer to ctDNA-guided adjuvant therapy or standard adjuvant therapy.
ClinicalTrials.gov
An ASCO 2025 interim analysis of 112 patients with resected stage I to III pancreatic adenocarcinoma reported that landmark postoperative ctDNA positivity predicted recurrence (HR 2.39; 95% CI 1.14 to 5.01), and longitudinal positivity was associated with shorter disease-free survival (HR 3.13).
Journal of Clinical Oncology
In the NeoCircle analysis of 116 patients with stage I to III breast cancer presented at ASCO 2025, postoperative molecular residual disease detected with a tumor-informed structural-variant assay was associated with a shorter relapse-free interval (HR 45.5; 95% CI 13.0 to 159.8) and shorter overall survival (HR 15.3; 95% CI 4.5 to 52.9).
Journal of Clinical Oncology
An ASCO 2025 preliminary report from MONSTAR-SCREEN-3, with 114 patients across 15 cancer types as of December 2024, found baseline ctDNA in 41 of 41 tested patients and postoperative month-1 MRD positivity in 10 of 28, including colorectal, gastric, head and neck, renal cell, esophageal, and pancreatic cancers.
Journal of Clinical Oncology
The ASCO 2025 preliminary MONSTAR-SCREEN-3 report enrolled 22 patients with gastric cancer and 8 with esophageal cancer among 114 patients across 15 cancer types.
Journal of Clinical Oncology
A Blood Advances article dated March 25, 2025, reviews measurable residual disease in adult ALL and notes that blinatumomab is indicated for MRD-positive B-cell ALL and, on the basis of the E1910 overall-survival result, is also used in newly diagnosed Philadelphia-negative ALL regardless of MRD response.
Blood Advances
In the final MRD analysis of the observational BESPOKE CRC study presented at ASCO GI 2025, ctDNA positivity in the postoperative window was associated with inferior disease-free survival in stage II disease (HR 10.4) and stage III disease (HR 10.1) among patients with a result in that window.
Journal of Clinical Oncology
In the observational alpha-CORRECT cohort of 124 patients with stage III colorectal cancer presented at ASCO GI 2025, a tumor-informed assay using up to 200 variants found that ctDNA positivity during surveillance was associated with recurrence (HR 49.6; 95% CI 16.6 to 148.3), with a median lead time of 10.4 months before a clinical diagnosis of recurrence.
Journal of Clinical Oncology
In the phase 3 ZEST trial, reported at SABCS 2024, enrollment stopped early after 1,901 patients had a tumor-informed ctDNA result and only 40 were randomized; of 147 patients with ctDNA detected, 72 (49%) already had radiographic recurrence on staging before randomization.
Clinical Cancer Research
A 2025 methods report describes DETECTION-2 (ISRCTN13695430), a feasibility randomization of patients with resected stage IIB, IIC, or IIIA melanoma to standard adjuvant therapy or to ctDNA monitoring with treatment if ctDNA is detected, and states that eight UK sites opened between November 27 and December 23, 2024.
EJC Skin Cancer
The ESMO 2024 IMpower010 ctDNA update reported that chemotherapy converted 62% of patients who were ctDNA-positive after surgery to ctDNA-negative, and that this clearance was associated with longer disease-free survival.
Annals of Oncology
At ESMO 2024, an updated IMpower010 analysis of resected stage II to IIIA non-small cell lung cancer reported that postoperative ctDNA positivity was a negative prognostic factor for disease-free survival after at least 5 years of follow-up, and that disease-free survival was longer with atezolizumab than with best supportive care in both ctDNA-positive and ctDNA-negative groups.
Annals of Oncology