ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2026
Adjuvant treatment intensity in circulating tumour DNA-negative colorectal cancer: a systematic review and reconstructed individual patient data meta-analysis.
Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposePostoperative circulating tumour DNA (ctDNA) is strongly prognostic after curative-intent surgery, but whether a negative result identifies patients with colorectal cancer (CRC) who can safely receive less-intensive adjuvant management remains uncertain. We synthesised prospective comparative evidence using reconstructed individual patient data (r-IPD), distinguishing the types of treatment contrast that have been studied.
methodsPubMed/MEDLINE, Google Scholar, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched through August 2025, and the structured databases and trial registry were updated to 1 October 2026. Time-to-event data for postoperative ctDNA-negative patients were reconstructed from published Kaplan-Meier curves. CRC analyses were organised by type of contrast: omission of chemotherapy, treatment duration, or addition of an investigational agent to standard chemotherapy. A pooled estimate across contrasts was reported as an exploratory summary.
resultsThirteen studies involving 9552 patients were included; r-IPD were reconstructed for 5323 ctDNA-negative patients, including 4236 with CRC from five studies. Hazard ratios (HRs) favoured more-intensive management for chemotherapy versus observation in the non-randomised GALAXY registry (HR 0.72, 95% confidence interval [CI] 0.52-0.99) and for 6 versus 3 months of chemotherapy in IDEA-France (HR 0.75, 95% CI 0.58-0.97), whereas adding an investigational agent to standard chemotherapy in three randomised trials did not show a clear benefit (HR 0.95, 95% CI 0.75-1.20). The exploratory pooled estimate was HR 0.84 (95% CI 0.73-0.96; I
conclusionsCurrent evidence does not support omission or broad de-escalation of adjuvant therapy solely because postoperative ctDNA is negative. The association with treatment intensity depended on the type of contrast, complete omission has been examined only in non-randomised data, and absolute differences were small. Research registration PROSPERO registration number: CRD420251153449.
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