Comparison of longitudinal circulating tumor DNA (ctDNA) and carcinoembryonic antigen (CEA) for post-operative risk stratification in colorectal cancer (CRC).
Year: 2026
Type: conference-abstract
Abstract: 3637 Background: ctDNA is a reliable biomarker that outperforms CEA for detecting molecular residual disease in CRC. However, the relative prognostic performance of these biomarkers across post-operative timepoints is not fully elucidated. Characterizing these temporal dynamics can provide essential insights for optimizing biomarker-guided surveillance. Methods: CEA and ctDNA (Signatera, Natera, Inc.) data at 12, 24, 36, 48, 72, and 96 weeks (wk) post-surgery from patients (pt) enrolled on the CIRCULATE-Japan GALAXY study were used to perform landmarked analyses. Disease-free survival (DFS) and overall survival (OS) were evaluated among pts who were event-free at each landmark. Hazard ratios (HRs) were estimated using Cox models adjusted for clinicopathological factors. Temporal trends in prognostic strength were assessed using weighted meta-regression across post-operative timepoints. Results: Of the 2,825 pts with CRC [84% stage I-III, 16% stage IV; median age 69 years (range 24-95)], 49% were female; 43% received adjuvant chemotherapy while 57% went directly to surveillance. At all evaluated landmarks, ctDNA- and CEA-positivity were associated with markedly higher risk of recurrence and death compared with ctDNA- and CEA-negativity, respectively. In DFS analyses, ctDNA outperformed CEA with substantially higher HRs at all landmarks (Table 1). The prognostic strength of ctDNA increased over time, with HRs increasing from 15.15 at 12 wks to 36.87 at 72 wks post-surgery and 32.31 through 96 wks. In contrast, CEA demonstrated modest and relatively stable DFS HRs across landmarks (range 2.04 to 3.43). Meta-regression analyses demonstrated a significant temporal strengthening of ctDNA’s prognostic performance for DFS (β:0.011 per wk, p=0.004), whereas no significant temporal trend was observed for CEA (p=0.33). In OS analyses, ctDNA positivity conferred high mortality risk at all landmarks, with HRs ranging from 8.40 to 14.15 (Table 1). Despite increasing prognostic association of CEA with OS at later landmarks, its HRs were lower than those of ctDNA. Conclusions: ctDNA-positivity consistently outperforms CEA in predicting disease recurrence and OS. ctDNA provides strong risk stratification at early postoperative time points, and its prognostic accuracy continually improves during longitudinal surveillance, confirming its superior performance for early risk assessment and personalized serial disease monitoring during surveillance. Clinical trial information: UMIN000039205. DFS and OS hazard ratios and ranges for ctDNA and CEA at all landmarks. Landmark ctDNA DFS CEA DFS ctDNA OS CEA OS 12 wk 15.15*** 2.68*** 8.4*** 3.65*** 24 wk 18.4*** 2.23*** 12.74*** 4.16*** 36 wk 19.36*** 2.04*** 9.81*** 5.41*** 48 wk 23.95*** 2.77*** 12.26*** 6.3*** 72 wk 36.87*** 3.43*** 14.15*** 8.72*** 96 wk 32.31*** 2.71* 8.45** 14.67*** *p<0.05, **p<0.001, ***p<0.0001.
Source: Journal of Clinical Oncology
Authors: Eiji Oki, Koji Ando, Hideaki Bando, Yoshiaki Nakamura, Daisuke Kotani, Saori Mishima, Darryl Nousome, Arkarachai Fungtammasan, Rama S. Madhurapantula, Charuta C. Palsuledesai, Robert William Lentz, Adham A. Jurdi, Minetta C. Liu, Hiroya Taniguchi, Jun Watanabe, Takeshi Kato, Yusuke Suwa, Keiji Hirata, Naoya Akazawa, Takayuki Yoshino
Institutions: Kyushu University, Kyushu University Hospital, National Cancer Center Hospital East, University of Oxford, Natera (United States), Aichi Cancer Center, Kansai Medical University, Osaka National Hospital, Yokohama City University Medical Center, University of Occupational and Environmental Health Japan, Sendai Medical Center, Sendai City Medical Center, Sendai Open Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7162486834
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