Who this is for
ctDNA colon cancer testing is becoming an important question for patients after bowel cancer surgery.
“Doctor, my bowel cancer has been removed. Do I really need chemotherapy, or is there a way to know whether the cancer is likely to come back?”
This article is for people with stage II colon cancer who have had surgery and are wondering whether a blood test can help guide chemotherapy decisions.
Clinical observation
Recently, I reviewed a 56-year-old mother of two who held a demanding executive position. She had undergone successful surgery for stage II colon cancer. The tumour had been completely removed, but the pathology report contained several high-risk features.
Her immediate concern was understandable.
“If I have chemotherapy, will I lose my hair? Will I be able to continue working?”
The first part of the discussion was relatively straightforward. The chemotherapy commonly used in this situation—capecitabine or fluoropyrimidine-based treatment—does not usually cause significant hair loss. Most patients continue working and maintaining their normal activities, although fatigue and other side effects can occur.
The more difficult question was whether she actually needed chemotherapy at all.
As medical oncologists, we face two opposite problems.
Sometimes we may be overtreating patients with stage II colon cancer who have already been cured by surgery alone.
At the same time, we may be undertreating some patients who appear low risk on paper but still have microscopic cancer cells remaining in the body.
For years, we have relied on pathological risk factors such as:
- Tumour stage
- Lymphovascular invasion
- Tumour grade
- Bowel obstruction
- Bowel perforation
- Number of lymph nodes examined
These factors remain important, but they are indirect measures of risk.
The question I increasingly ask myself is:
Am I overtreating some stage II cancers and undertreating others?
Could a simple blood test tell us whether microscopic cancer cells are still present after surgery?
This question has led to one of the most exciting developments in modern colon cancer care—the use of circulating tumour DNA (ctDNA).
Why this study matters
Even after a surgeon removes all visible cancer, microscopic disease can sometimes remain behind. Because of this, some patients may still be at risk of the cancer returning, even when their scans look clear.
These microscopic cancer cells cannot be seen on CT scans, PET scans, MRI scans, or routine blood tests.
This is known as minimal residual disease (MRD).
Circulating tumour DNA (ctDNA) testing looks for tiny fragments of tumour DNA that may still be detectable in the bloodstream after surgery.
The theory is simple.
- If ctDNA is detected, there may still be microscopic cancer cells remaining.
- If ctDNA is not detected, the likelihood of residual disease is lower.
Instead of deciding on chemotherapy purely based on pathology features, we may be able to use a patient’s individual ctDNA result to guide treatment decisions.
ctDNA Colon Cancer Testing After Surgery
Circulating tumour DNA, or ctDNA, testing looks for tiny fragments of tumour DNA that may still be detectable in the bloodstream after surgery.
What is the DYNAMIC study?
The DYNAMIC study was an Australian-led clinical trial that investigated whether ctDNA testing could guide chemotherapy decisions in patients with stage II colon cancer.
The goal was simple:
Could we safely reduce the number of patients receiving chemotherapy without increasing the risk of cancer recurrence?
Study methodology
Study Type
Phase II randomised controlled trial.
Number of Patients
455 patients.
Patient Population
Patients with completely resected stage II colon cancer.
Randomisation
Patients were assigned to one of two groups.
Standard Management Group
Doctors made chemotherapy recommendations based on traditional pathological risk factors.
These included:
- T4 tumours
- Lymphovascular invasion
- Poor differentiation
- Bowel obstruction
- Bowel perforation
- Inadequate lymph node assessment
ctDNA-Guided Group
Patients underwent postoperative ctDNA testing.
Treatment recommendations were based primarily on the blood test result.
- ctDNA positive → chemotherapy recommended
- ctDNA negative → observation recommended
What did the study find?
The results were remarkable.
Key result 1 – Chemotherapy Use
In the standard treatment group, 28% of patients received chemotherapy.
In the ctDNA-guided group, only 15% of patients received chemotherapy.
This represented almost a 50% reduction in chemotherapy use.
In simple terms, using the blood test helped many patients avoid chemotherapy after surgery.
Key result 2 – Recurrence-Free Survival
The key question was whether avoiding chemotherapy in some patients would increase the chance of cancer recurrence.
It did not.
After 2 years, the percentage of patients who remained free from cancer recurrence was:
- 5% in the ctDNA-guided group
- 4% in the standard treatment group
This means that fewer patients received chemotherapy, but the cancer outcomes remained almost the same.
Key result 3 – The blood test helped identify patients at higher risk
Patients with a positive ctDNA result after surgery had a higher risk of the cancer coming back.
In simple terms, if ctDNA is detected, it may be a warning sign that microscopic cancer cells are still present.
What does “Non-inferior” mean?
This is an important concept that often causes confusion.
Many people assume every clinical trial is trying to prove that a new treatment is better.
That was not the purpose of DYNAMIC.
Instead, the researchers asked:
Can we safely give less treatment without making outcomes worse?
Imagine two people arrive at the same destination.
One person drives for four hours.
The other arrives in two hours.
Both reach the destination safely.
The second approach may not necessarily be “better” in every way, but it is certainly more efficient.
This is what the DYNAMIC trial demonstrated.
The ctDNA-guided approach achieved essentially the same cancer outcomes while exposing fewer patients to chemotherapy.
That is what a successful non-inferiority study means.
What happens if ctDNA is positive?
This is where ctDNA becomes particularly powerful.
Multiple studies have shown that ctDNA positivity after surgery is one of the strongest predictors of cancer recurrence.
Importantly, patients with detectable ctDNA after surgery have a higher risk of the cancer returning compared with patients whose ctDNA is negative.
In many ways, ctDNA may be measuring something far more important than traditional pathology factors.
It may be providing direct evidence that microscopic cancer cells are still present.
What about stage III colon cancer?
The next logical question was whether ctDNA could help patients with stage III colon cancer.
Unlike stage II disease, stage III colon cancer routinely receives chemotherapy because cancer cells have already spread to lymph nodes.
However, not all stage III cancers behave the same way.
Some patients may be receiving more treatment than they need.
Others may require more intensive treatment than standard approaches provide.
This question has now been studied in the DYNAMIC-III study and several other international trials.
The aim is to determine whether ctDNA can personalise treatment intensity based on the presence or absence of measurable residual disease.
This represents one of the most important ongoing areas of colorectal cancer research.
An important limitation
Not all ctDNA blood tests are identical.
Different laboratories use different technologies.
Differences may include:
- Sensitivity
- Specificity
- Number of mutations analysed
- Tumour-informed testing
- Tumour-naïve testing
As a result, a negative result from one platform may not necessarily be equivalent to a negative result from another platform.
This is why ctDNA results should always be interpreted in the context of the patient’s pathology, imaging and overall clinical situation.
What this means for patients today
For decades, decisions about chemotherapy after colon cancer surgery were based largely on pathology reports.
However, ctDNA testing offers something different.
It may help show whether tiny fragments of tumour DNA are still detectable in the bloodstream after surgery.
Because of this, ctDNA testing may help some patients avoid chemotherapy when the risk of recurrence appears low.
At the same time, it may help identify patients who have a higher risk of the cancer returning and may benefit from additional treatment.
Overall, the future of colon cancer treatment is moving towards more personalised care.
Rather than treating all patients the same way, we are beginning to tailor treatment based on the behaviour of each individual cancer.
For patients who have completed surgery and chemotherapy, our article on exercise after colon cancer treatment may also be helpful.
Key takeaways
- ctDNA testing is a specialised blood test that can help detect minimal residual disease after colon cancer surgery.
- In the Australian-led DYNAMIC trial of 455 patients with stage II colon cancer, ctDNA-guided treatment reduced chemotherapy use from 28% to 15%.
- Cancer outcomes remained similar between ctDNA-guided management and standard management, supporting this as a successful non-inferiority study.
- A positive ctDNA result is associated with a higher risk of recurrence, but ctDNA should be interpreted alongside pathology, imaging, tumour stage, and specialist oncology advice.
References
- Baxter NN, Kennedy EB, Bergsland E, et al. Adjuvant therapy for stage II colon cancer: ASCO guideline update. J Clin Oncol. 2022;40(8):892-910. doi:10.1200/JCO.21.02538
- Argilés G, Tabernero J, Labianca R, et al. Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(10):1291-1305. doi:10.1016/j.annonc.2020.06.022
- Tie J, Cohen JD, Lahouel K, et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N Engl J Med. 2022;386(24):2261-2272. doi:10.1056/NEJMoa2200075
- Tie J, Wang Y, Lo SN, et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial. Nat Med. 2025;31(5):1509-1518. doi:10.1038/s41591-025-03579-w
- Nakamura Y, Watanabe J, Akazawa N, et al. ctDNA-based molecular residual disease and survival in resectable colorectal cancer. Nat Med. 2024;30(11):3272-3283. doi:10.1038/s41591-024-03254-6
- Tie J, Wang Y, Loree JM, et al; AGITG DYNAMIC-III Study Group. Circulating tumor DNA-guided adjuvant therapy in locally advanced colon cancer: the randomized phase 2/3 DYNAMIC-III trial. Nat Med. 2025;31(12):4291-4300. doi:10.1038/s41591-025-04030-w
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. Version 2.2026. National Comprehensive Cancer Network; 2026. Accessed June 19, 2026.
Frequently asked questions (FAQ)
- Will chemotherapy for stage II colon cancer cause hair loss?
Usually not. The most commonly used chemotherapy treatments for stage II colon cancer, such as capecitabine, do not typically cause significant hair loss.
- What is ctDNA?
Circulating tumour DNA (ctDNA) consists of tiny fragments of cancer DNA that can sometimes be detected in the bloodstream after surgery.
- If my ctDNA test is negative, does that mean I am cured?
Not necessarily. A negative result is reassuring and suggests a lower risk of recurrence, but ongoing surveillance remains essential.
- If my ctDNA is positive, does that mean my cancer will definitely return?
No. However, the risk of recurrence is significantly higher compared with patients who remain ctDNA negative.
- Is ctDNA testing available in Australia?
Yes. Several commercial ctDNA platforms are available in Australia, although access and funding arrangements vary.
- Should every patient with stage II colon cancer have ctDNA testing?
This remains an evolving area. Many oncologists now consider ctDNA testing when discussing adjuvant chemotherapy decisions, particularly in patients where the benefit of chemotherapy is uncertain.
Disclaimer: This article is intended for educational purposes only and should not replace personalised medical advice. Treatment decisions should always be discussed with your treating oncologist, taking into account your pathology, imaging findings, ctDNA results and overall clinical circumstances.
Dr Dilanka De Silva
MBBS, MRCP(UK), MRCP(UK SCE Oncology), FRACP, PhD
Medical Oncologist & Cancer Genetics Physician
Memorial Sloan Kettering Cancer Center Fellow (New York, USA)