{"entity":{"id":"idea-ctdna-guided-adjuvant-crc","kind":"idea","name":"ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer","aka":[],"tldr":"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.","asOf":"2026-09-07","links":[{"label":"DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer (New England Journal of Medicine 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"},{"label":"GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold (Nature Medicine 2023)","url":"https://doi.org/10.1038/s41591-022-02115-4"}],"tags":[],"related":["colorectal-roadmap","idea-crc-ctdna-de-escalation-beyond-stage-ii"],"cancers":["colorectal"],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":["signatera","folfox"],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":["dynamic","circulate-japan"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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.","test":"CIRCULATE-US / NRG-GI005 (COBRA) style randomised platform with pre-specified escalation arms; DFS primary endpoint.","maturity":"being-tested-at-scale"},"route":"/ideas/idea-ctdna-guided-adjuvant-crc/","neighbours":{"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"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","route":"/roadmaps/colorectal-roadmap/"},{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/"},{"id":"diagnostics-roadmap","kind":"roadmap","name":"Diagnostics roadmap: stains → gene panels → blood tests that decide treatment","route":"/roadmaps/diagnostics-roadmap/"}],"idea":[{"id":"idea-tr2-ctdna-mrd-qualification","kind":"idea","name":"Formally qualify tumour-DNA blood tests as a surrogate endpoint for adjuvant trials","route":"/ideas/idea-tr2-ctdna-mrd-qualification/"},{"id":"idea-crc-ctdna-de-escalation-beyond-stage-ii","kind":"idea","name":"Take ctDNA-guided de-escalation beyond stage II, and stop escalating on a positive result until a trial says it helps","route":"/ideas/idea-crc-ctdna-de-escalation-beyond-stage-ii/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"rectal-cancer","kind":"cancer","name":"Rectal cancer","route":"/cancers/rectal-cancer/"}],"technology":[{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"drug":[{"id":"folfox","kind":"drug","name":"FOLFOX (5-FU, leucovorin, oxaliplatin)","route":"/drugs/folfox/"},{"id":"signatera","kind":"drug","name":"Signatera","route":"/drugs/signatera/"}],"term":[{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"}],"trial":[{"id":"circulate-japan","kind":"trial","name":"CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)","route":"/trials/circulate-japan/"},{"id":"dynamic","kind":"trial","name":"DYNAMIC","route":"/trials/dynamic/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-metastasis-biology","kind":"bottleneck","name":"Metastasis is understood least and studied last","route":"/bottlenecks/b-metastasis-biology/"}],"paper":[{"id":"paper-dynamic-nejm-2022","kind":"paper","name":"DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer","route":"/key-papers/paper-dynamic-nejm-2022/"},{"id":"paper-galaxy-signatera-nat-med-2023","kind":"paper","name":"GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold","route":"/key-papers/paper-galaxy-signatera-nat-med-2023/"}]}}