Circulating Tumor DNA for Detecting Molecular Residual Disease (MRD) in Stage II/III Colorectal Cancer
Final Analysis of the BESPOKE CRC Sub-Cohort – ASCO GI 2025
Tags: #PSMCRC #ASCOGI2025 #ctDNA #PrecisionOncology
Circulating Tumor DNA in Colorectal Cancer | ASCO GI 2025 InsightsGI 2025 Insights.
📌 Study Background and Significance
Stage II/III colorectal cancer (CRC) remains a major clinical challenge due to the risk of silent recurrence after curative-intent treatment. The early detection of molecular residual disease (MRD) using circulating tumor DNA (ctDNA) may revolutionize therapeutic approaches, enabling personalized interventions and reducing unnecessary treatments.
The BESPOKE CRC study, presented at ASCO GI 2025, explored ctDNA as a highly prognostic biomarker for disease-free survival (DFS) and its role in guiding clinical decision-making.
📊 Authors and Affiliations
📍 First Author: Purvi Shah, Virginia Cancer Institute
📍 Co-Authors: Vasily Aushev, Joe Ensor, Stephanie Sanchez, Christopher Wang, Timothy Cannon, Lyudmyla Berim, Trevor Feinstein, Axel Grothey, Joseph McCollom, Sujith Kalmadi, Ahmed Zakari, Farshid Dayyani, Don Gravenor, Minetta Liu, Adham Jurdi, Alexey Aleshin, Janelle Meyer, Saima Sharif, Scott Kopetz
📍 Institutional Affiliations: Virginia Cancer Institute, Natera, Inc., Alabama Oncology, Inova Schar Cancer Institute, Rutgers Cancer Institute of New Jersey, Piedmont Cancer Institute, West Cancer Center and Research Institute, Parkview Cancer Institute, Ironwood Cancer & Research Centers, AdventHealth Cancer Institute, University of California, Irvine Medical Center, Baptist Cancer Center, Oregon Oncology Specialists, University of Iowa, The University of Texas MD Anderson Cancer Center
📌 ASCO GI 2025 Presentation Details:
🔹 Session: Oral Abstract Session C – Colorectal and Anal Cancer
🔹 Track: Tumor Biology, Biomarkers, and Pathology
🔹 Clinical Trial Registration Number: NCT04264702
🔹 DOI: 10.1200/JCO.2025.43.4_suppl.15
🔹 Citation: J Clin Oncol 43, 2025 (suppl 4; abstr 15)
Circulating Tumor DNA in Colorectal Cancer | ASCO GI 2025 Insights
🧬 Methods
The BESPOKE CRC study enrolled 1,001 patients with stage II/III CRC who underwent curative-intent surgery. The Signatera assay, a personalized tumor-informed mPCR-NGS ctDNA test, was used for longitudinal monitoring.
🔬 Plasma Collection Time Points:
✅ MRD Window: 2–12 weeks post-surgery
✅ Surveillance Window: Post-adjuvant chemotherapy (ACT) or 12 weeks post-surgery for observation-only patients
The correlation between ctDNA status and DFS was evaluated to determine its prognostic value.
📈 Key Findings
1️ – Adjuvant Chemotherapy (ACT) Utilization
📊 62.4% of patients received ACT
✔ Stage II: 25.9% (115/443)
✔ Stage III: 91.3% (510/558)
2️ – ctDNA Positivity and Disease-Free Survival (DFS)
🔬 MRD Window Analysis (Median Follow-up: 23.15 months)
✔ Stage II: 8.1% (34/420) of patients were ctDNA-positive
✔ Stage III: 24.9% (126/505) of patients were ctDNA-positive
Recurrence Risk (Hazard Ratio – HR):
📉 Stage II: HR = 10.4 (p < 0.0001)
📉 Stage III: HR = 10.1 (p < 0.0001)
3️ – DFS at 18 and 24 Months
| ctDNA Status | 18-Month DFS | 24-Month DFS |
| MRD-Negative | 93.0% | 91.7% |
| MRD-Positive | 44.4% | 41.4% |
4️ – Surveillance: Observation vs. ACT-Treated Patients
✔ Observed ctDNA-positive patients had a 34.9x higher recurrence risk (p < 0.0001).
✔ ACT-treated ctDNA-positive patients had a 131.4x higher recurrence risk (p < 0.0001).
🔍 Conclusions
✅ ctDNA is a highly prognostic biomarker for DFS and could revolutionize the management of colorectal cancer in the precision oncology era.
✅ ctDNA-positive patients may benefit from intensified adjuvant therapy, including chemotherapy or immunotherapy combinations.
✅ ctDNA-negative patients could be eligible for treatment de-escalation strategies, avoiding unnecessary toxicity while maintaining efficacy.
Circulating Tumor DNA in Colorectal Cancer | ASCO GI 2025 Insights
🏥 Clinical Implications & Future Directions
🔹 Personalized Treatment Strategies: ctDNA-positive patients should receive more aggressive treatment.
🔹 Reducing Chemotherapy Exposure: ctDNA-negative patients may avoid overtreatment and its associated toxicities.
🔹 Next Steps in Research: Future trials should explore immunotherapy and targeted therapies for ctDNA-positive patients.
📌 References:
📖 Shah, P., et al. J Clin Oncol 43, 2025 (suppl 4; abstr 15) – DOI: 10.1200/JCO.2025.43.4_suppl.15
📑 Clinical Trial Registration: NCT04264702
📢 Join the Conversation!
💬 What do these findings mean for peritoneal surface malignancies (PSM CRC)? How can ctDNA reshape clinical management? Comment below!
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