# ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer

Source: https://onco.cc/ideas/idea-ctdna-guided-adjuvant-crc/  
OnCo record `idea-ctdna-guided-adjuvant-crc` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Use a blood test after surgery to decide who gets chemotherapy: spare the negatives, and find something that actually works for the positives.

## Summary

The idea is to make a post-operative ctDNA test such as Signatera the default decision tool for adjuvant therapy in stage II to III colon cancer, sparing ctDNA-negative patients chemotherapy and escalating positives to FOLFOX with or without a biology-matched agent. DYNAMIC showed that ctDNA-negative stage II patients can safely omit chemotherapy, while ALTAIR within CIRCULATE-Japan showed that late-line trifluridine and tipiracil does not help positives. The rationale is that post-operative ctDNA predicts recurrence far more strongly than any clinicopathological feature. Being tested at scale in CIRCULATE-US and COBRA-style platforms, it addresses the bottlenecks of dormant cells and minimal residual disease and of metastasis being studied last.

## Fields

- Kind: Idea
- Last checked: 2026-09-07
- Hypothesis: A ctDNA-directed strategy (omit in negatives; escalate positives with FOLFOX ± a biology-matched agent) yields non-inferior 3-year DFS with half the chemotherapy exposure across stage II-III.
- Rationale: Post-operative ctDNA has a hazard ratio for recurrence near 10 and outperforms every clinicopathologic feature.
- Proposed test: CIRCULATE-US / NRG-GI005 (COBRA) style randomised platform with pre-specified escalation arms; DFS primary endpoint.
- Maturity: being-tested-at-scale

## Sources

- DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer (New England Journal of Medicine 2022): https://doi.org/10.1056/NEJMoa2200075
- GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold (Nature Medicine 2023): https://doi.org/10.1038/s41591-022-02115-4

## 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/), [ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment](https://onco.cc/roadmaps/ctdna-tests/), [Diagnostics roadmap: stains → gene panels → blood tests that decide treatment](https://onco.cc/roadmaps/diagnostics-roadmap/)
- ideas: [Formally qualify tumour-DNA blood tests as a surrogate endpoint for adjuvant trials](https://onco.cc/ideas/idea-tr2-ctdna-mrd-qualification/), [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/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Rectal cancer](https://onco.cc/cancers/rectal-cancer/)
- technologies: [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- drugs: [FOLFOX (5-FU, leucovorin, oxaliplatin)](https://onco.cc/drugs/folfox/), [Signatera](https://onco.cc/drugs/signatera/)
- terms: [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/)
- trials: [CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)](https://onco.cc/trials/circulate-japan/), [DYNAMIC](https://onco.cc/trials/dynamic/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/), [Metastasis is understood least and studied last](https://onco.cc/bottlenecks/b-metastasis-biology/)
- key papers: [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/)

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