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A blood test after surgery already lets stage II colon cancer patients skip chemotherapy safely. The same test in stage III would spare far more people, and the unproven half, giving more chemotherapy to those who test positive, has so far changed nothing.
DYNAMIC randomised 455 patients with stage II colon cancer and cut adjuvant chemotherapy use from 28 to 15 percent with two-year recurrence-free survival of 93.5 against 92.4 percent, non-inferior against a margin of 8.5 percentage points. GALAXY, in 1,039 patients across stages II to IV, found a hazard ratio of 10.0 for recurrence with a positive test four weeks after surgery and showed adjuvant chemotherapy benefit concentrated in the positives (hazard ratio 6.59).
Both halves of the strategy are unfinished. De-escalation is proven only in stage II, where QUASAR put the absolute survival benefit of chemotherapy at 3.6 percent to begin with; the far larger prize is the stage III population where six months of oxaliplatin is routine and 60 to 70 percent of patients are cured by surgery alone. Escalation has no positive trial at all: the ALTAIR arm of CIRCULATE-Japan, which added trifluridine-tipiracil for ctDNA-positive patients, did not improve outcomes, and this idea takes that as evidence that a more intensive version of the same drug class is the wrong response to a positive test.
The predictive half of the ctDNA case: chemotherapy after surgery helps the patients whose blood test is positive and appears to do little for those whose test is negative, which is the rationale for the randomised CIRCULATE trials now running in Japan, the United States and Europe.
De-escalation guided by a blood test is now proven in stage II colon cancer, and is the template for the stage III and rectal trials that follow; the unsolved half is what to do for the positives, whose recurrence-free survival remains the worst in the trial even after chemotherapy.
The largest de-escalation exercise in adjuvant oncology, and the reason a patient with a T3 N1 colon cancer is now offered four cycles of CAPOX rather than twelve of FOLFOX, with a fraction of the neuropathy.
Minimal residual disease became measurable in solid tumours, and the DYNAMIC and CIRCULATE trials that followed turned the measurement into a treatment decision.
Shares Duration of adjuvant chemotherapy for stage III colon cancer (the IDEA collaboration), CAPOX (capecitabine, oxaliplatin), Neoadjuvant / adjuvant / perioperative, FOLFOX (5-FU, leucovorin, oxaliplatin) and the tag colorectal-evidence.
Shares Duration of adjuvant chemotherapy for stage III colon cancer (the IDEA collaboration), Neoadjuvant / adjuvant / perioperative, 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, FOLFOX (5-FU, leucovorin, oxaliplatin) and the tag colorectal-evidence.
Shares Minimal / molecular residual disease (MRD), Circulating tumour DNA (ctDNA), 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, FOLFOX (5-FU, leucovorin, oxaliplatin) and the tag colorectal-evidence.
Shares CAPOX (capecitabine, oxaliplatin), Neoadjuvant / adjuvant / perioperative, 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, FOLFOX (5-FU, leucovorin, oxaliplatin) and the tag colorectal-evidence.
Shares Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer (DYNAMIC), Neoadjuvant / adjuvant / perioperative, 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, Toxicity and quality of life are undervalued and the tag colorectal-evidence.
Shares CAPOX (capecitabine, oxaliplatin), 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, FOLFOX (5-FU, leucovorin, oxaliplatin), Toxicity and quality of life are undervalued and the tag colorectal-evidence.
Shares Neoadjuvant / adjuvant / perioperative, 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, Colon cancer (adenocarcinoma of the colon), Colorectal cancer and the tag colorectal-evidence.
Shares Neoadjuvant / adjuvant / perioperative, 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, Toxicity and quality of life are undervalued, Colorectal cancer and the tag colorectal-evidence.