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The aim of this study was to investigate the prognostic value of postoperative ctDNA in patients with stage III colon cancer who received adjuvant chemotherapy (ACT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PROVENC3 was a multicentre prospective study of patients who underwent resection of pathological stage III colon cancer. Blood samples were collected at a median of 13 (interquartile range 4\u201320)\u2005days after resection. The presence of minimal residual disease was determined using Labcorp\u00ae Plasma Detect\u2122, a novel tumour-informed whole genome sequencing (WGS) ctDNA test. The primary endpoint was 3-year time to recurrence (TTR). ctDNA status was further combined with pathological risk status to investigate the combined prognostic value.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The median follow-up of the 209 patients who were included was 40\u2005months. In total, 28 patients (13%) had detectable ctDNA after surgery. Postoperative ctDNA-positive patients had a worse TTR compared with ctDNA-negative patients (HR 6.2 (95% c.i. 3.4 to 11.2); P &amp;lt; 0.001). Of all ctDNA-positive patients, 36% did not develop recurrences during 3-year follow-up. Detectable ctDNA after ACT was associated with worse TTR (HR 7.9 (95% c.i. 3.9 to 15.9); P &amp;lt; 0.001). ctDNA status combined with pathological risk classification resulted in a 3-year recurrence risk that varied from 82% for pathological high-risk (pT4\/N2) ctDNA-positive patients to 7% for pathological low-risk (pT1\u20133 N1) ctDNA-negative patients (HR 28.5 (95% c.i. 10.5 to 77.2); P &amp;lt; 0.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Postoperative ctDNA detection using a tumour-informed WGS test improves prognosis stratification in stage III colon cancer and may help to personalize adjuvant treatment.<\/jats:p>\n                  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