# ctDNA MRD positivity (molecular residual disease after curative treatment)

Source: https://onco.cc/biomarkers/ctdna-mrd-positive/  
OnCo record `ctdna-mrd-positive` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A ctDNA MRD test looks for the tumour's own mutations in blood after surgery. Detection predicts relapse months before scans, and in 2026 the FDA approved Signatera as the companion test selecting bladder cancer patients for adjuvant atezolizumab.

## Summary

Tumour-informed assays (Signatera, RaDaR, NeXT Personal) sequence the tumour first and track a personalised set of variants in plasma; tumour-naive assays (Guardant Reveal) use mutations and methylation without a tumour sample. A positive result is any detection above the assay's calling threshold, reported as detected or not detected with a level. IMvigor011 showed a survival benefit for atezolizumab over placebo in ctDNA-positive muscle-invasive bladder cancer after cystectomy, and the FDA list carries Signatera CDx as the companion diagnostic for Tecentriq in that setting (P260004, 15 May 2026); the Tecentriq label read on 20 May 2026 predates the indication text in the openFDA copy, so the threshold here is quoted from the FDA list. In colorectal cancer the DYNAMIC trial and the ongoing CIRCULATE trials use ctDNA to guide adjuvant chemotherapy. As a genome-wide readout it sits under no target.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: ctDNA MRD; ctDNA positive; ctDNA-positive; molecular residual disease; MRD-positive ctDNA; Signatera positive; ctDNA detected after surgery
- Tags: biomarker; genome-wide; ctdna

## Notes

- Triple-negative breast cancer: post-neoadjuvant ctDNA detection carried a distant disease-free survival hazard ratio of 2.99 in BRE12-158 (Radovich 2020) and 3.71 independent of residual cancer burden in an 80-patient registry, positive in 33% overall and 57% of RCB-III (Stecklein 2023); every pathological complete responder in I-SPY 2 was ctDNA-negative (Magbanua 2021). Prospective surveillance in c-TRAK TN detected ctDNA in 27.3% by 12 months but 72% already had metastases and pembrolizumab cleared none (Turner 2023); brain-only relapse escapes detection (1 of 6; Garcia-Murillas 2019). No TNBC approval uses ctDNA; it is a stratification factor in ASCENT-05 and the ZEST design.
- Pancreatic ductal adenocarcinoma: ctDNA is detectable in 43 to 62% of localised disease before surgery and in 37 to 49% of patients after it, where it predicts recurrence with 90% sensitivity and 88% specificity at a median lead time of 84 days (Groot 2019) or 6.5 months against computed tomography (Sausen 2015); all 13 patients with postoperative ctDNA recurred, including 7 given adjuvant gemcitabine (Lee 2019). In advanced disease detection means overall survival 6.5 against 19.0 months, with the allele fraction grading the risk (Pietrasz 2017) and exosome DNA adding to it (Bernard 2019). Most assays track only KRAS codon 12, 13 and 61, so the 6 to 12% of KRAS wild-type tumours are invisible; no pancreatic approval or guideline uses ctDNA.
- Colorectal cancer: this is the disease where tumour-informed residual disease testing was invented and where it has its only randomised evidence. Postoperative detection carries recurrence hazard ratios of 7 to 18 (Tie 2016, Reinert 2019, Henriksen 2022) and week-4 positivity a hazard ratio of 10 with 18-month disease-free survival of 38.4% against 90.5% (Kotani 2023); detection after adjuvant chemotherapy is worse still (hazard ratios 17.5 and 50.8) and 16 of 20 such patients relapsed despite treatment. DYNAMIC showed that a ctDNA-guided policy cut adjuvant chemotherapy use from 28% to 15% with non-inferior two-year recurrence-free survival in stage II colon cancer (Tie 2022). What is still missing is evidence that escalating treatment on a positive result improves survival, and a negative result is not a cure: 16 of 164 ctDNA-negative stage II patients recurred (Tie 2016).
- Lymphoma: plasma sequencing does three different jobs here. It genotypes, including the cell-of-origin call, directly from blood; it measures burden at diagnosis, which correlated with clinical indices and independently predicted outcome across 92 lymphoma patients profiled by CAPP-Seq (Scherer 2016); and it measures residual disease, where PhasED-seq, which uses several somatic mutations carried on the same DNA fragment, reaches the parts-per-million range and found residual disease in a further 25% of participants who were negative by the earlier method after two cycles, and those participants did worse (Kurtz 2021). What is missing is a decision: no lymphoma approval depends on a ctDNA result and no randomised trial has yet changed treatment on one.

## Sources

- FDA: List of FDA-Authorized Companion Diagnostic Devices: https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools
- TECENTRIQ prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6fa682c9-a312-4932-9831-f286908660ee
- Scherer et al., Sci Transl Med 2016: ctDNA genotyping classifies cell of origin and tracks genome evolution in lymphoma (92 patients): https://doi.org/10.1126/scitranslmed.aai8545
- Kurtz et al., Nat Biotechnol 2021: PhasED-seq, phased variants for residual disease detection in B-cell lymphoma (213 participants): https://doi.org/10.1038/s41587-021-00981-w

## Connected records

- biomarkers: [Circulating tumour DNA fraction (and what a negative plasma result means)](https://onco.cc/biomarkers/ctdna-tumour-fraction/), [ESR1 mutation (ligand-binding domain, usually in ctDNA)](https://onco.cc/biomarkers/esr1-mutation-ctdna/), [TMB-high (tumour mutational burden >= 10 mutations per megabase)](https://onco.cc/biomarkers/tmb-high/)
- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Early triple-negative breast cancer](https://onco.cc/cancers/tnbc-early/), [Hodgkin lymphoma](https://onco.cc/cancers/hodgkin-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/resectable-pdac/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [ctDNA monitoring in lymphoma (PhasED-seq, clonoSEQ)](https://onco.cc/technologies/ctdna-lymphoma-monitoring/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [clonoSEQ](https://onco.cc/drugs/clonoseq/), [Guardant Reveal](https://onco.cc/drugs/guardant-reveal/), [Oncodetect](https://onco.cc/drugs/oncodetect/), [RaDaR](https://onco.cc/drugs/radar-mrd/), [Signatera](https://onco.cc/drugs/signatera/)
- terms: [Cell-free DNA (cfDNA)](https://onco.cc/terms/cfdna/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Tumour-informed versus tumour-naive ctDNA assays](https://onco.cc/terms/tumour-informed-assay/)
- key papers: [Analysis of plasma cell-free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer](https://onco.cc/key-papers/paper-reinert-ctdna-ultradeep-sequencing-colorectal-jama-oncol-2019/), [Assessment of molecular relapse detection in early-stage breast cancer](https://onco.cc/key-papers/paper-garcia-murillas-molecular-relapse-detection-jama-oncol-2019/), [Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial](https://onco.cc/key-papers/paper-radovich-ctdna-ctc-bre12-158-jama-oncol-2020/), [Circulating nucleic acids are associated with outcomes of patients with pancreatic cancer](https://onco.cc/key-papers/paper-bernard-ctdna-exodna-pancreatic-gastroenterology-2019/), [Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer](https://onco.cc/key-papers/paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016/), [Circulating tumor DNA as a clinical test in resected pancreatic cancer](https://onco.cc/key-papers/paper-groot-kras-ctdna-clinical-test-resected-pancreatic-ccr-2019/), [Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer](https://onco.cc/key-papers/paper-lee-ctdna-adjuvant-benefit-localized-pancreatic-ann-oncol-2019/), [Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival](https://onco.cc/key-papers/paper-magbanua-ispy2-ctdna-neoadjuvant-ann-oncol-2021/), [Circulating tumor DNA in stage III colorectal cancer, beyond minimal residual disease detection, toward assessment of adjuvant therapy efficacy and clinical behavior of recurrences](https://onco.cc/key-papers/paper-henriksen-ctdna-stage-iii-colorectal-improve-it-ccr-2022/), [Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial (TRIUMPH)](https://onco.cc/key-papers/paper-nakamura-triumph-ctdna-pertuzumab-trastuzumab-her2-colorectal-nat-med-2021/), [Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients](https://onco.cc/key-papers/paper-sausen-ctdna-pancreatic-resection-nat-commun-2015/), [ctDNA and residual cancer burden are prognostic in triple-negative breast cancer patients with residual disease](https://onco.cc/key-papers/paper-stecklein-ctdna-rcb-tnbc-residual-disease-npj-2023/), [DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer](https://onco.cc/key-papers/paper-dynamic-nejm-2022/), [GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold](https://onco.cc/key-papers/paper-galaxy-signatera-nat-med-2023/), [Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer](https://onco.cc/key-papers/paper-garcia-murillas-ctdna-mutation-tracking-stm-2015/), [Plasma circulating tumor DNA in pancreatic cancer patients is a prognostic marker](https://onco.cc/key-papers/paper-pietrasz-ctdna-prognostic-pancreatic-ccr-2017/), [Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer](https://onco.cc/key-papers/paper-cavallone-tnbc-ctdna-neoadjuvant-sci-rep-2020/), [Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer](https://onco.cc/key-papers/paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023/)

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