# ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment

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

## TL;DR

Blood carries fragments of tumour DNA. This roadmap follows the tests that read them, from the first sighting in 1948 to blood tests that now choose a drug, spare chemotherapy, or screen for many cancers at once, and it lists the readouts to watch next.

## Summary

Circulating tumour DNA (ctDNA) testing has three jobs, and each is at a different stage. Genotyping from blood is settled: the cobas EGFR plasma test became the first FDA-approved liquid biopsy in June 2016, and Guardant360 CDx and FoundationOne Liquid CDx followed in August 2020 as broad companion diagnostics. Residual disease testing after surgery has crossed from prognosis to action: DYNAMIC showed in 2022 that a ctDNA-guided approach halves chemotherapy in stage II colon cancer without harm, and in May 2026 the FDA approved adjuvant atezolizumab for ctDNA-positive muscle-invasive bladder cancer on IMvigor011, the first drug approval that depends on a ctDNA residual disease result. Escalation for a positive test is not yet proven: ALTAIR missed its endpoint and the MERMAID lung trials closed small.

Multi-cancer early detection is the least settled. Shield won FDA approval for colorectal screening in July 2024 on a single-cancer claim. Galleri has one randomised trial behind it: NHS-Galleri did not reduce stage III and IV cancers combined, its primary endpoint, while reporting fewer stage IV diagnoses, and the FDA's advisory panel considers the test on 23 September 2026. The NCI's Vanguard study is the first randomised US test of the approach and runs to 2029.

The steps below are grouped by what the evidence allowed at the time. The 'What to watch' list carries registry completion dates and meeting dates as their sources state them. Tumour-informed assays (built from the patient's own tumour sequence) and tumour-naive assays (fixed panels, often methylation-based) compete on sensitivity, turnaround and cost; the roadmap treats that split as a running theme rather than an era.

## Fields

- Kind: Roadmap
- Last checked: 2026-09-21
- Also known as: Liquid biopsy roadmap; MRD testing roadmap; Multi-cancer early detection roadmap
- Tags: ctdna; liquid-biopsy; mrd; mced

## Notes

- How this stays current: run `npm run ctdna:watch`. The script reads this roadmap, lists every trial it references with its corpus status, checks each NCT id against the ClinicalTrials.gov v2 API for overall status and completion dates, and searches Europe PMC for papers on the trial acronyms published since the roadmap's asOf date. Anything it prints that this page does not say is an edit to make; then move asOf forward.
- Dates in 'What to watch' are quoted from registries and releases and are not predictions. Registry completion dates move, and a company release is used only for a meeting date or a readout date, never for a result the paper has not yet reported.

## Sources

- Mandel and Metais: nucleic acids in human blood plasma (C R Seances Soc Biol Fil 1948): https://europepmc.org/article/MED/18875018
- Leon et al.: free DNA in the serum of cancer patients and the effect of therapy (Cancer Research 1977): https://europepmc.org/article/MED/837366
- Diehl et al.: circulating mutant DNA to assess tumour dynamics (Nature Medicine 2008): https://europepmc.org/article/MED/18670422
- Dawson et al.: analysis of circulating tumour DNA to monitor metastatic breast cancer (NEJM 2013): https://europepmc.org/article/MED/23484797
- Bettegowda et al.: detection of circulating tumour DNA in early- and late-stage human malignancies (Science Translational Medicine 2014): https://europepmc.org/article/MED/24553385
- Tie et al.: ctDNA detects minimal residual disease and predicts recurrence in stage II colon cancer (Science Translational Medicine 2016): https://europepmc.org/article/MED/27384348
- AACR: FDA approves first liquid biopsy test for lung cancer patients, 1 June 2016: https://www.aacr.org/blog/2016/06/06/fda-approval-liquid-biopsy-test-lung-cancer/
- FDA PMA P150044: cobas EGFR Mutation Test v2 (tissue and plasma): https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P150044
- FDA PMA P200010: Guardant360 CDx, approved 7 August 2020: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P200010
- FDA PMA P190032: FoundationOne Liquid CDx, approved 26 August 2020: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P190032
- Natera: final Medicare coverage for Signatera in stage II-III colorectal cancer, 3 September 2020: https://www.natera.com/company/news/natera-receives-final-medicare-coverage-for-its-signatera-mrd-test-in-stage-ii-iii-colorectal-cancer-2/
- CMS article A58456: MolDX minimal residual disease testing for solid tumour cancers (revision effective 1 January 2026): https://www.cms.gov/medicare-coverage-database/view/article.aspx?articleId=58456
- DYNAMIC: ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM, 16 June 2022): https://europepmc.org/article/MED/35657320
- DYNAMIC five-year outcomes (Nature Medicine 2025): https://europepmc.org/article/MED/40055522
- GALAXY: molecular residual disease and efficacy of adjuvant chemotherapy in colorectal cancer (Nature Medicine 2023): https://europepmc.org/article/MED/36646802
- CIRCULATE-Japan: ctDNA-guided adaptive platform trials, design of GALAXY, VEGA and ALTAIR (Cancer Science 2021): https://europepmc.org/article/MED/33931919
- ALTAIR: post-adjuvant trifluridine/tipiracil in ctDNA-positive resected colorectal cancer, primary endpoint not met (Nature Medicine 2026): https://europepmc.org/article/MED/42260101
- IMvigor011: ctDNA-guided adjuvant atezolizumab in muscle-invasive bladder cancer (NEJM 2025): https://europepmc.org/article/MED/41124204
- FDA approves atezolizumab for adjuvant treatment of muscle invasive bladder cancer with ctDNA molecular residual disease, 15 May 2026: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-adjuvant-treatment-muscle-invasive-bladder-cancer-patients-molecular
- PATHFINDER: blood-based tests for multicancer early detection (The Lancet 2023): https://europepmc.org/article/MED/37805216
- FDA PMA P230009: Shield blood-based colorectal cancer screening test, approved 26 July 2024: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P230009
- NHS-Galleri: performance of a multi-cancer early detection test across three annual rounds (Nature Medicine, 22 September 2026): https://europepmc.org/article/MED/42773209
- GRAIL: full results from the NHS-Galleri trial, 30 May 2026: https://grail.com/press-releases/grail-reports-full-results-from-nhs-galleri-trial-demonstrating-substantial-reduction-in-stage-iv-cancer-diagnoses-at-2026-asco-annual-meeting/
- GRAIL: PATHFINDER 2 results in more than 35,000 participants, 31 May 2026: https://grail.com/press-releases/grail-presents-pathfinder-2-results-of-more-than-35000-participants-showing-the-galleri-test-substantially-increased-cancer-detection-with-robust-performance-and-favorable-safety-at-2026-a/
- GRAIL: FDA advisory committee meeting on the Galleri PMA set for 23 September 2026: https://grail.com/press-releases/grail-announces-fda-advisory-committee-meeting-to-review-premarket-approval-application-for-the-galleri-multi-cancer-early-detection-test/
- ClinicalTrials.gov NCT06995898: https://clinicaltrials.gov/study/NCT06995898
- ClinicalTrials.gov NCT05174169: https://clinicaltrials.gov/study/NCT05174169
- ClinicalTrials.gov NCT04050345: https://clinicaltrials.gov/study/NCT04050345
- ClinicalTrials.gov NCT04660344: https://clinicaltrials.gov/study/NCT04660344
- ClinicalTrials.gov NCT05155605: https://clinicaltrials.gov/study/NCT05155605

## Connected records

- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/), [Diagnostics roadmap: stains → gene panels → blood tests that decide treatment](https://onco.cc/roadmaps/diagnostics-roadmap/), [Early detection roadmap: organ screening → blood tests for many cancers](https://onco.cc/roadmaps/early-detection-roadmap/), [Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials](https://onco.cc/roadmaps/gallbladder-cancer-roadmap/), [Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/), [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/), [Paths to cures: interception, eradication, control](https://onco.cc/roadmaps/cure-paths/), [Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch](https://onco.cc/roadmaps/prostate-roadmap/), [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- pairings: [ctDNA MRD → adjuvant therapy decision](https://onco.cc/pairings/ctdna-mrd-to-adjuvant/)
- ideas: [A 28-day national pathway for people with a positive multi-cancer blood test](https://onco.cc/ideas/idea-prev-mced-positive-resolution-pathway/), [A ctDNA residual disease-guided adjuvant trial after gallbladder cancer resection](https://onco.cc/ideas/idea-gbc-ctdna-residual-disease-guided-adjuvant-trial/), [Certified reference samples to benchmark every tumour-DNA blood test](https://onco.cc/ideas/idea-tr2-ctdna-reference-plasma/), [ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative](https://onco.cc/ideas/idea-tnbc-ctdna-guided-adjuvant-decisions/), [ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer](https://onco.cc/ideas/idea-ctdna-guided-adjuvant-crc/), [Formally qualify tumour-DNA blood tests as a surrogate endpoint for adjuvant trials](https://onco.cc/ideas/idea-tr2-ctdna-mrd-qualification/), [Make resistance a diagnosis: sequence at every progression and choose the next line from what the tumour became](https://onco.cc/ideas/idea-lung-resistance-directed-sequencing-at-every-progression/), [Pay for residual disease tests only inside a trial or registry](https://onco.cc/ideas/idea-bio2-mrd-coverage-with-evidence/), [Push residual disease detection a hundredfold deeper with whole-genome methods](https://onco.cc/ideas/idea-bio2-whole-genome-mrd-depth/), [Reference materials and open proficiency testing for residual disease tests](https://onco.cc/ideas/idea-bio2-mrd-reference-standards/), [Take ctDNA-guided de-escalation beyond stage II, and stop escalating on a positive result until a trial says it helps](https://onco.cc/ideas/idea-crc-ctdna-de-escalation-beyond-stage-ii/), [Track clones in blood with methylation patterns instead of mutations](https://onco.cc/ideas/idea-bio1-methylation-clone-tracking/), [Use circulating tumour DNA instead of the interim scan to decide what happens next](https://onco.cc/ideas/lymphoma-ev-ctdna-instead-of-the-interim-scan/), [Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it](https://onco.cc/ideas/idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine/)
- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/), [Early Detection & Screening](https://onco.cc/fronts/early-detection/)
- technologies: [Cell-free DNA methylation tests](https://onco.cc/technologies/cfdna-methylation-testing/), [cfDNA fragmentomics](https://onco.cc/technologies/fragmentomics/), [Companion diagnostics](https://onco.cc/technologies/companion-diagnostic/), [Continuous and near-continuous ctDNA monitoring](https://onco.cc/technologies/continuous-ctdna-monitoring/), [DNA methylation profiling](https://onco.cc/technologies/methylation-profiling/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [Multi-cancer early detection (MCED)](https://onco.cc/technologies/mced/), [Residual disease kinetics (BCR-ABL halving and ctDNA slopes)](https://onco.cc/technologies/mrd-kinetics-models/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [cobas EGFR Mutation Test v2](https://onco.cc/drugs/cobas-egfr-mutation-test/), [Erlotinib](https://onco.cc/drugs/erlotinib/), [FoundationOne CDx / Liquid CDx](https://onco.cc/drugs/foundationone-cdx/), [Galleri](https://onco.cc/drugs/galleri/), [Guardant Reveal](https://onco.cc/drugs/guardant-reveal/), [Guardant360 CDx](https://onco.cc/drugs/guardant360-cdx/), [Osimertinib](https://onco.cc/drugs/osimertinib/), [RaDaR](https://onco.cc/drugs/radar-mrd/), [Shield](https://onco.cc/drugs/shield/), [Signatera](https://onco.cc/drugs/signatera/), [Trifluridine/tipiracil](https://onco.cc/drugs/trifluridine-tipiracil/)
- companies: [DELFI Diagnostics](https://onco.cc/companies/delfi-diagnostics/), [Exact Sciences (Abbott)](https://onco.cc/companies/exact-sciences/), [Foundation Medicine (Roche)](https://onco.cc/companies/foundation-medicine/), [Freenome](https://onco.cc/companies/freenome/), [GRAIL](https://onco.cc/companies/grail/), [Guardant Health](https://onco.cc/companies/guardant-health/), [Natera](https://onco.cc/companies/natera/), [NRG Oncology](https://onco.cc/companies/nrg-oncology/), [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- terms: [Cell-free DNA (cfDNA)](https://onco.cc/terms/cfdna/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [De-escalation, escalation and response-adapted therapy](https://onco.cc/terms/de-escalation/), [FDA laboratory-developed test (LDT) rule](https://onco.cc/terms/fda-ldt-rule/), [Medicare coverage with evidence development](https://onco.cc/terms/medicare-ced/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Positive predictive value (PPV)](https://onco.cc/terms/ppv/), [Stage shift](https://onco.cc/terms/stage-shift/), [Surrogate endpoint validation: which stand-ins have earned trust](https://onco.cc/terms/surrogate-validation/), [Tumour-informed versus tumour-naive ctDNA assays](https://onco.cc/terms/tumour-informed-assay/)
- trials: [BESPOKE CRC](https://onco.cc/trials/bespoke-crc/), [CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)](https://onco.cc/trials/circulate-japan/), [CIRCULATE-US](https://onco.cc/trials/circulate-us/), [DYNAMIC](https://onco.cc/trials/dynamic/), [ECLIPSE (Shield blood test)](https://onco.cc/trials/eclipse-shield/), [IMvigor011](https://onco.cc/trials/imvigor011/), [MERMAID-1](https://onco.cc/trials/mermaid-1/), [MERMAID-2](https://onco.cc/trials/mermaid-2/), [NHS-Galleri](https://onco.cc/trials/nhs-galleri/), [PATHFINDER 2](https://onco.cc/trials/pathfinder-2/), [TRACC](https://onco.cc/trials/tracc/), [Vanguard Study (NCI Cancer Screening Research Network)](https://onco.cc/trials/vanguard-study/)
- people: [Alberto Bardelli](https://onco.cc/people/alberto-bardelli/), [Deborah Schrag](https://onco.cc/people/deb-schrag/), [Jeanne Tie](https://onco.cc/people/jeanne-tie/), [Klaus Pantel](https://onco.cc/people/klaus-pantel/), [Nickolas Papadopoulos](https://onco.cc/people/nickolas-papadopoulos/), [Nitzan Rosenfeld](https://onco.cc/people/nitzan-rosenfeld/), [Peter Sasieni](https://onco.cc/people/peter-sasieni/), [Sarah-Jane Dawson](https://onco.cc/people/dawson-sarah-jane/), [Thomas Powles](https://onco.cc/people/thomas-powles/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/)
- key papers: [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 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/), [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/), [IMvigor011: using a blood test for leftover cancer to decide who gets immunotherapy after bladder surgery](https://onco.cc/key-papers/paper-imvigor011-nejm-2025/), [NHS-Galleri: design of the largest randomised trial of a multi-cancer blood test](https://onco.cc/key-papers/paper-nhs-galleri-design-cancers-2022/), [PATHFINDER: the first prospective test of a multi-cancer blood test in people without symptoms](https://onco.cc/key-papers/paper-pathfinder-lancet-2023/), [Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial](https://onco.cc/key-papers/paper-nhs-galleri-performance-nat-med-2026/), [Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution](https://onco.cc/key-papers/paper-abbosh-phylogenetic-ctdna-lung-cancer-nature-2017/), [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/)
- pathways: [Clonal evolution & minimal residual disease](https://onco.cc/pathways/clonal-evolution/), [Clonal haematopoiesis (CHIP)](https://onco.cc/pathways/clonal-haematopoiesis/)
- institutions: [National Cancer Institute (NIH)](https://onco.cc/institutions/nci/)

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