Real-world Monitoring of ctDNA Reliably Predicts Cancer Recurrence and Treatment Efficacy in Patients with Resected Stages I-III Colon Cancer
Year: 2025
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: In this study, we evaluate the utility of ctDNA analysis in a large cohort of patients for whom ctDNA testing was ordered commercially with real-world application. SUMMARY BACKGROUND DATA: Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for assessing post-surgical molecular residual disease (MRD) and response to treatment. METHODS: A real-world data analysis was performed using commercial ctDNA testing (SignateraTM) from patients (N=795, n=5,971 plasma samples) with stage I-III colon cancer treated at multiple US institutions. The association of ctDNA detection within the MRD window, during surveillance, and the impact of ACT was correlated with patient outcomes. RESULTS: ctDNA-positive patients during the MRD window and surveillance showed significantly shorter DFS compared to ctDNA-negative patients (hazard ratio (HR): 9.85, P<0.0001; HR: 26.91, P<0.0001). Multivariate analysis of the MRD window revealed ctDNA-positivity as the most significant factor associated with inferior DFS (adjHR: 7.7, P<0.001). MRD-positive patients who received ACT showed improved DFS compared to patients observed post-surgery (adjHR: 6.1, FDR adj P=0.0007). No ACT benefit was observed in MRD-negative patients (adj HR: 1.20, FDR adj P=0.768). On evaluating ctDNA dynamics from MRD to surveillance, patients who remained ctDNA-positive or converted from negative to positive showed a significantly inferior DFS (HR: 34.40, P<0.0001; HR: 13.65, P<0.0001) compared to persistently ctDNA-negative patients. CONCLUSIONS: Postsurgical ctDNA detection is prognostic of relapse and potentially predictive of ACT benefit in patients with resectable colon cancer, which may enable personalized surveillance, intervention, and/or trial options, ultimately improving patient outcomes.
Source: Annals of Surgery
Authors: Stacey A. Cohen, Vasily N. Aushev, George Laliotis, Iktej S. Jabbal, Arun Nagarajan, Chongkai Wang, Marwan Fakih, Saima Sharif, Fadhel Alyunis, Mohamedtaki A. Tejani, Ali Alqahtani, John Marshall, Jeremy Chang, Gregory Botta, Kevin Manage, Giby V. George, Shruti Sharma, Meenakshi Malhotra, Sreenivasa Chandana, Shoshana Mehler, Bradley G. Somer, Ellie Babadi, Christina Wu, Diana Hanna, Anusha Chidharla, Anup Kasi, Elham Vosoughi, Farshid Dayyani, Katrina Pedersen, Robert Edward Briski, George Azzi, Vatsala Katiyar, Abigail Chan, Vivek Sharma, Aditya Shreenivas, Sakti Chakrabarti, Jacob Fuqua, Midhun Malla, Blase Polite, Alisha H. Bent, Matthew Rabinowitz, Adham Jurdi, Minetta C. Liu, Alexey Aleshin, Scott Kopetz
Institutions: University of Washington, Fred Hutch Cancer Center, AdventHealth Sebring, Cleveland Clinic, Cleveland Clinic Florida, City Of Hope National Medical Center, University of Iowa, AdventHealth, Georgetown University, Georgetown University Medical Center, Georgetown Lombardi Comprehensive Cancer Center, Moores Cancer Center, West Cancer Center, Mayo Clinic Hospital, USC Norris Comprehensive Cancer Center, The University of Kansas Cancer Center, University of California, San Francisco, University of California, Irvine, UC Irvine Chao Family Comprehensive Cancer Center, Washington University in St. Louis, Holy Cross Hospital, Illinois CancerCare, University of Louisville, Medical College of Wisconsin Cancer Center, University Hospitals of Cleveland, University Hospitals Seidman Cancer Center, West Virginia University, West Virginia University Hospitals, University of Alabama at Birmingham, UAB Medicine, University of Chicago, The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4413040398