Dynamic-III Study Insights: Optimizing Adjuvant Chemotherapy De-escalation in Stage III Colon Cancer Using ctDNA Monitoring

Liquid Biopsies Show Promise in Guiding Chemotherapy for Colon Cancer

LONDON, UK – October 19, 2025 – groundbreaking research presented at the European Society for Medical Oncology (ESMO) 2025 meeting indicates that a simple blood test, known as a liquid biopsy, may help doctors determine which patients with Stage III colon cancer will benefit moast from chemotherapy following surgery. This advancement offers the potential to minimize needless treatment and its associated side effects.

The DYNAMIC-III Trial and Circulating Tumor DNA

The Phase 3 DYNAMIC-III trial, a collaborative effort between the Australian Gastro-Intestinal Trials Group (AGITG) and the canadian Cancer Trials Group (CCTG), focused on the use of a highly sensitive circulating tumor DNA (ctDNA) test. This test detects minute traces of cancer DNA shed into the bloodstream. The aim was to reduce or eliminate chemotherapy in patients who tested negative for ctDNA, effectively avoiding overtreatment.

According to Professor Marco Gerlinger, Professor of Gastrointestinal Cancer Medicine at Barts Cancer Institute, approximately 50% of patients with Stage III colon cancer could potentially be cured by surgery alone. currently, however, all lymph node-positive patients routinely receive chemotherapy, leading to significant side effects for individuals who might have been cured by surgery alone.

Study Findings and Ongoing Research

While the overall trial results were not statistically significant in demonstrating a clear benefit of ctDNA-guided de-escalation of chemotherapy, a subgroup analysis showed promising results for patients with low-risk Stage III tumors – those with up to three positive lymph nodes. In this group, omitting or reducing chemotherapy intensity did not appear to compromise treatment outcomes.

Professor Andrew Beggs, MRC Senior Clinical Fellow and Consultant Colorectal Surgeon at the University of Birmingham, emphasized that liquid biopsy technology is rapidly evolving. He suggested that the current tests may not be sensitive enough to accurately identify all patients who can safely avoid chemotherapy, but that further research and technological advancements are likely to improve precision.

“It may well be that the test they used was not sensitive enough to pick the right patients for chemotherapy,” Professor Beggs stated. “Liquid biopsy technology is developing very fast, and this study relies on follow-up data that has taken several years to generate.”

Here’s a swift overview of key findings:

Key Aspect	Details
Trial Name	DYNAMIC-III
Test Used	High-sensitivity circulating tumor DNA (ctDNA) test
Target Population	Stage III colon cancer patients
Primary Goal	Reduce or omit chemotherapy in ctDNA-negative patients
Subgroup Benefit	Low-risk Stage III tumors (≤3 positive lymph nodes)

Did You Know? According to the American Cancer society,approximately 153,020 new cases of colon and rectal cancer will be diagnosed in the United States in 2024.

Implications for Future Treatment

Although the DYNAMIC-III trial isn’t instantly changing clinical practice for all Stage III colon cancer patients, it represents a crucial step towards personalized cancer treatment. The findings suggest that a combination of ctDNA testing and other risk stratification approaches may ultimately allow doctors to tailor chemotherapy regimens to each patient’s individual needs, maximizing effectiveness while minimizing harm.

“This study adds evidence that it is likely we will be able to better select patients for chemotherapy after bowel cancer surgery,” Professor Beggs concluded, “by only selecting those who really need it, removing the side effects for those who are found not to need chemotherapy in the end.”

Pro Tip: If you or a loved one is facing a cancer diagnosis, openly discuss all treatment options and potential side effects with your oncologist.

Understanding Liquid Biopsies

Liquid biopsies represent a significant shift in cancer management. Traditionally, diagnosing and monitoring cancer has relied on invasive tissue biopsies. liquid biopsies, on the other hand, analyze circulating biomarkers – such as ctDNA, circulating tumor cells (CTCs), and exosomes – found in blood or other bodily fluids. This non-invasive approach offers several advantages, including the ability to monitor treatment response in real-time, detect minimal residual disease, and identify genetic mutations that may drive cancer progression. The cost of these tests has been decreasing, with an average cost of $2,000 – $5,000 in 2023 per test, making them increasingly accessible.

frequently Asked Questions About Colon Cancer and Liquid Biopsies

• What is a liquid biopsy for colon cancer? A liquid biopsy is a blood test that looks for cancer cells or pieces of DNA from tumors in the blood.
• Is chemotherapy always necessary for Stage III colon cancer? Not necessarily. Research suggests that some patients may be cured by surgery alone, and chemotherapy can be avoided in select cases.
• How does ctDNA testing work? ctDNA testing detects tiny fragments of cancer DNA circulating in the bloodstream, providing insights into the presence and characteristics of the tumor.
• What are the potential benefits of using liquid biopsies? Liquid biopsies can help personalize treatment, reduce overtreatment, monitor treatment response, and detect cancer recurrence earlier.
• Are liquid biopsies widely available? While increasingly available, liquid biopsies are not yet standard of care for all colon cancer patients and are typically used within clinical trials or specialized cancer centers.
• What are the limitations of ctDNA testing in colon cancer? The DYNAMIC-III trial showed that ctDNA testing alone isn’t perfect at predicting which patients can skip chemotherapy, and further research is needed.

What are your thoughts on the potential of liquid biopsies to revolutionize cancer treatment? Do you think personalized medicine will become the norm in the future?

Share your comments below and spread the word!

What are the key inclusion criteria for patients eligible for ctDNA-guided chemotherapy de-escalation based on the Dynamic-III trial?

Understanding ctDNA and its Role in Colon Cancer Management

Circulating tumor DNA (ctDNA) is a revolutionary biomarker in oncology, especially gaining traction in the management of Stage III colon cancer. It represents fragments of DNA shed by tumor cells into the bloodstream. Detecting and monitoring ctDNA allows us to gain a dynamic understanding of a patient’s disease status – beyond customary staging. This is the core principle behind studies like dynamic-III, aiming to personalize adjuvant chemotherapy regimens. Traditional approaches to colon cancer treatment frequently enough involve a standardized 6-month course of FOLFOX or CAPOX. Though, this “one-size-fits-all” approach doesn’t account for individual responses and can expose patients to unnecessary toxicity.

The Dynamic-III Trial: A Paradigm Shift in Adjuvant Therapy

The dynamic-III trial (and its predecessor, Dynamic-I & II) investigated whether ctDNA monitoring could safely guide chemotherapy de-escalation in patients with stage III colon cancer post-surgical resection. The study focused on patients with microsatellite stable (MSS) tumors, as ctDNA’s predictive value is strongest in this subgroup.

Here’s a breakdown of the Dynamic-III approach:

* Baseline ctDNA Assessment: Following surgery, patients underwent ctDNA testing.

* ctDNA Negative, Chemotherapy De-escalation: Patients with undetectable ctDNA after surgery were eligible for a shortened course of adjuvant chemotherapy (3 months).

* ctDNA Positive, Standard Chemotherapy: Patients with detectable ctDNA received the standard 6-month chemotherapy regimen.

* Dynamic Monitoring: ctDNA was monitored throughout treatment. If ctDNA became detectable during the shortened chemotherapy course, treatment was extended to 6 months.

The initial results demonstrated a non-inferior disease-free survival (DFS) rate with the ctDNA-guided approach compared to standard chemotherapy,suggesting that de-escalated chemotherapy is a viable option for select patients.

Benefits of ctDNA-Guided Chemotherapy De-escalation

The potential benefits of utilizing ctDNA monitoring to personalize adjuvant treatment for Stage III colon cancer are meaningful:

* Reduced Toxicity: Shorter chemotherapy durations minimize exposure to debilitating side effects like neuropathy, mucositis, and myelosuppression. This improves quality of life for patients.

* Cost-Effectiveness: Decreasing the duration of chemotherapy translates to lower healthcare costs.

* Personalized Medicine: ctDNA allows for a tailored approach, treating patients based on their individual risk profile rather than a generalized protocol.

* Early Detection of Recurrence: Ongoing ctDNA monitoring can detect minimal residual disease (MRD) and possibly identify recurrence before it becomes clinically apparent, allowing for earlier intervention. This is a key aspect of cancer recurrence monitoring.

Practical Considerations for Implementing ctDNA Monitoring

Implementing ctDNA monitoring in clinical practice requires careful consideration:

1. Assay Validation: Ensure the ctDNA assay used is highly sensitive and specific. Different assays have varying performance characteristics.
2. Turnaround Time: Rapid turnaround time for ctDNA results is crucial for timely treatment decisions.
3. Multidisciplinary Collaboration: Effective implementation requires close collaboration between surgeons, medical oncologists, pathologists, and molecular biologists.
4. Patient Education: Patients need to understand the purpose of ctDNA testing and how the results will influence their treatment plan.
5. Insurance Coverage: Access to ctDNA testing may be limited by insurance coverage. Advocacy for broader coverage is essential.

ctDNA and Microsatellite Instability (MSI) Status

It’s crucial to understand the interplay between ctDNA and MSI status. Microsatellite instability-high (MSI-H) tumors are frequently enough associated with a better prognosis and may not benefit as much from ctDNA-guided de-escalation, as they are more responsive to immunotherapy. The Dynamic-III trial specifically focused on MSS colon cancer as ctDNA is a more reliable predictor of recurrence in this subgroup. Thus,MSI testing is a prerequisite for considering ctDNA monitoring.

Real-World Submission & case example

At Archyde Oncology, we’ve seen firsthand the impact of ctDNA monitoring. A 62-year-old male patient diagnosed with Stage III colon cancer (MSS) underwent accomplished surgical resection. Post-operative ctDNA testing was negative. He was offered a 3-month course of adjuvant FOLFOX chemotherapy. he tolerated treatment well,