BACKGROUND
Adjuvant chemotherapy (ACT) provides limited benefit in unselected stage II colon cancer patients (pts). Postoperative ctDNA has higher prognostic value than classical clinical or molecular markers but has not been proven to predict benefit from ACT.
METHODS
Pts with UICC II, pMMR/MSS colon cancer were tested for ctDNA using an academic, tumor-informed, NGS based test (Stasik, Front Genet 2022). ctDNA positive (pos) pts were randomized (planned 2:1) to CHEMO (6 mo capecitabine [cape] or 3-6 mo cape+oxaliplatin) vs observation without ACT (OBS). ctDNA negative (neg) pts were randomized 1:4 to OBS vs OFF-STUDY. Patients in OBS and their investigators remained blinded to the ctDNA status. The primary endpoint was DFS in ctDNApos pts (CHEMO vs. OBS), the TTR was reported as 3-y recurrence rate. Differences were tested using one-sided log-rank tests. The planned sample size was 1,540 randomized pts assuming 10% ctDNApos. Because the funding period expired, the trial ended early and was finally analyzed.
RESULTS
From 06/2020 to 07/2025, 2,126 pts were screened 138 sites in Germany/Austria. The ctDNApos rate was lower than expected among randomized pts (2.9%) and screened but not randomized pts (4.3%). Overall, 1,396 pts were randomized: 1,083 to OFF-STUDY, 287 to OBS (15 ctDNApos), and 26 pts to CHEMO (all ctDNApos). Median age was 64 y, 63% were male. Classical risk factors were present in 9.5% (4.8% pT4, 5.0% unplanned resection). In CHEMO, 21/26 pts (81%) started cape, 33% of them received oxaliplatin, median no of cycles was 6. There was one treatment-related death. DFS and OS were significantly higher in ctDNAneg vs ctDNApos pts (3-y-DFS 87% vs 52%, HR 0.23 [95%CI 0.13-0.43], p < 0.001; 3-y-OS 98% vs 88%, HR 0.18 [95%CI 0.05-0.61], p = 0.001). In the per-protocol (PP) analysis (excluding CHEMO pts not treated), CHEMO improved recurrence rates and DFS compared to ctDNApos/OBS (3-y recurrence rate19% vs 62%, HR 0.21 [95%CI 0.06-0.80], p = 0.009; 3-y-DFS 77% vs 38%, HR 0.28 [95%CI 0.09-0.94], p = 0.022). Cancer-specific survival (CSS) was numerically higher with CHEMO (3-y-CSS 100% vs 84%, HR 0.25 [95%CI 0.03-2.44]). In the ITT cohort (including the non-treated pts), the differences between arms were not significant (3-y recurrence rate 35% vs 62%, HR 0.48 [95%CI 0.17-1.33], p = 0.08; 3-y-DFS 61% vs 38%, HR 0.52 [95%CI 0.20-1.39], p = 0.12; 3-y-CSS 94% vs 84%, HR 0.40 [95%CI 0.07-2.38], p = 0.15).
CONCLUSION
This is the first prospective randomized trial demonstrating that ctDNA guided ACT improves TTR and DFS in stage II colon cancer pts without clinical risk factors, supporting ctDNA testing for adjuvant decision making in the clinical practice. Limitations include the relatively low number of randomized ctDNApos pts, the sensitivity of the academic test developed 10 y ago and the reliance on PP analysis.
CLINICAL TRIAL INFORMATION
NCT04089631. This is an ASCO Meeting Abstract from the 2026 ASCO Annual Meeting II. This abstract does not include a full text component.
Author Affiliations
1Technical University Dresden, Medical Faculty Carl Gustav Carus, NCT/UCC/Medical Department I, Dresden, Germany; 2Technical University Dresden / Medical Faculty Carl Gustav Carus, Lab. Hematology, Dresden, Germany; 3COLOPREDICT Platform and Institute of Pathology, Georgius Agricola Stiftung Ruhr, Ruhr-University Bochum, Bochum, Germany; 4Austrian Breast & Colorectal Cancer Study Group (ABCSG) and IIIrd Medical Department, Paracelsus Medical University, Salzburg, Austria; 5Hematology-Oncology Practice Hamburg (HOPE), Hamburg, Germany; 6Onkologische Schwerpunktpraxis, Dresden, Germany; 7University Medical Center Goettingen, Goettingen, Germany; 8Mannheim Cancer Center, University of Heidelberg, Mannheim, Germany; 9Outpatient Clinics for Hematology and Oncology, Münster, Germany; 10University of Wuerzburg, Surgical Department I, Wuerzburg, Germany; 11Klinikum Chemnitz, Department of Hematology, Oncology, and Cellular Therapy, Chemnitz, Germany; 12Staedt. Klinikum Muenchen GmbH, Munich, Germany; 13Universitätsklinikum Marburg, Klinik für Innere Medizin, Marburg, Germany; 14Elblandklinikum Riesa, Riesa, Germany; 15National Center for Tumor Diseases (NCT) Dresden, Dresden, Germany; 16Institute of Pathology, Faculty of Medicine Carl Gustav Carus, Technical University Dresden, Dresden, Germany; 17COLOPREDICT Platform and Institute of Pathology, Ruhr-University, Bochum, Germany; 18COLOPREDICT Platform and Department of Hematology, Oncology and Palliative Care, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
