Utility of Circulating Tumor DNA to Assess Tumor Response in Patients with Locally Advanced Rectal Cancer Undergoing Neoadjuvant Therapy
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background: Circulating tumor (ct)DNA is a prognostic biomarker in gastrointestinal malignancies. In rectal cancer, its utility to inform perioperative management and predict recurrence, particularly in patients undergoing non-operative management (NOM), remains unclear. Studies are needed to clarify how post-neoadjuvant therapy (NAT) and post-surgical ctDNA status correlate with clinical outcomes in localized rectal cancer. Methods: We retrospectively analyzed ctDNA data from 220 patients with rectal cancer using a personalized tumor-informed assay (Signatera™, Natera, Inc., Austin, TX, USA). Of these, 148 (67.3%) underwent NAT followed by surgery, and 72 (32.7%) underwent NAT followed by NOM. We assessed associations between post-NAT ctDNA status and survival outcomes. In the surgical cohort, we examined associations between post-operative ctDNA status and clinical response, pathological response, survival outcomes, and NAR scores. Results: In the surgical cohort, ctDNA positivity at the post-operative MRD timepoint was a strong predictor of recurrence, with an 88.3% relapse rate compared to 11.5% in ctDNA-negative patients (p < 0.001). Among the 64 NOM patients with post-NAT ctDNA, 21.9% (14/64) were ctDNA-positive, of whom 100% (14/14) relapsed (92.9% local-only), 13 relapsed by the time of data cut-off, and one relapsed 8 months after the cut-off. Only 10% (5/50) of the ctDNA-negative NOM patients experienced local recurrence (p < 0.0001). ctDNA positivity post-NAT was associated with inferior DFS (p = 0.003). Conclusion: ctDNA was a strong predictor of recurrence in rectal cancer, including in NOM settings. In NOM patients, ctDNA detected local recurrences, highlighting its potential to guide post-NAT surveillance and treatment.
Source: Cancers
Authors: Sakti Chakrabarti, Stacey A. Cohen, Antony Tin, Autumn Dangl, Ki Y. Chung, Mohamedtaki A. Tejani, Marwan G. Fakih, Sreenivasa R. Chandana, Colleen A. Donahue, Virgilio George, Midhun Malla, Vasily N. Aushev, Giby V. George, J. Bryce Ortiz, Whitney K. Herter, Arun Nagarajan, Benjamin A. Weinberg, Vivek R. Sharma, Gregory P. Botta, May Cho, Georges Azzi, Anup Kasi, Farshid Dayyani, Diana L. Hanna, Bradley G. Somer, Meenakshi Malhotra, Shruti Sharma, Adham Jurdi, Minetta C. Liu, Ron G. Landmann, Arvind Dasari
Institutions: University Hospitals Seidman Cancer Center, Case Western Reserve University, University of Washington, Fred Hutch Cancer Center, Natera (United States), Prisma Health, AdventHealth, City Of Hope National Medical Center, Medical University of South Carolina, University of Alabama at Birmingham, Cleveland Clinic Florida, MedStar Georgetown University Hospital, University of Louisville, Moores Cancer Center, University of California, Irvine, Holy Cross Hospital, University of Kansas Medical Center, University of California, Irvine Medical Center, University of Southern California, USC Norris Comprehensive Cancer Center, Baptist MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7128602932