Who this is for
MSI-high colon cancer immunotherapy is becoming an important topic for patients with stage III colon cancer after surgery.
“I have had surgery for stage III colon cancer. My doctor told me the cancer is MSI-high or dMMR. I have heard immunotherapy works well in advanced bowel cancer. Could immunotherapy reduce the chance of my cancer coming back?”
This article is for patients with:
- Stage III colon cancer
- Cancer found in nearby lymph nodes
- MSI-high or dMMR colon cancer
- Lynch syndrome-associated colon cancer
- Patients considering treatment after surgery
- Patients seeking a colon cancer second opinion
A Clinical Observation
Several years ago, I looked after a gentleman with Lynch syndrome-associated colon cancer.
His surgery was successful, and he received the standard treatment available at the time: chemotherapy.
Unfortunately, despite doing everything right, his cancer returned several years later.
That experience stayed with me because MSI-high colon cancers have always seemed different. We have known for years that these cancers can respond remarkably well to immunotherapy when they become advanced. Yet after surgery, chemotherapy has remained the standard treatment.
The ATOMIC study asked a simple but important question:
If immunotherapy works so well in advanced MSI-high colon cancer, why wait until the cancer comes back before using it?
What This Study Means
Not all colon cancers are the same.
A small proportion of bowel cancers are classified as MSI-high (microsatellite instability-high) or mismatch repair deficient (dMMR).
This result is important because it may influence both your family’s cancer risk and your treatment options.
It may indicate Lynch syndrome.
Lynch syndrome is the most common hereditary bowel cancer syndrome.
People with Lynch syndrome have an increased risk of developing colon cancer, endometrial cancer and several other cancers. Identifying Lynch syndrome can also be important for family members.
It may affect treatment choices.
MSI-high cancers behave differently from most colon cancers.
In patients with Stage IV MSI-high colon cancer, immunotherapy has dramatically improved outcomes and is often preferred over traditional chemotherapy.
The ATOMIC study investigated whether immunotherapy could also improve outcomes when given after surgery for Stage III disease.
What Was the ATOMIC Study?
The ATOMIC study was a large international Phase III clinical trial involving 712 patients with Stage III MSI-high colon cancer.
Who Took Part?
Patients were recruited predominantly through major cancer centres in the United States and Germany.
After surgery, patients were randomly assigned to receive:
Standard Treatment
- Modified FOLFOX6 chemotherapy, also called mFOLFOX6or
Experimental Treatment
- FOLFOX chemotherapy
- Plus atezolizumab immunotherapy
- Followed by additional atezolizumab treatment
The results were encouraging.
Key Results
- Immunotherapy reduced the chance of the cancer coming back.
Patients who received atezolizumab with chemotherapy had about a 50% lower risk of cancer recurrence or death compared with patients who received chemotherapy alone. - More patients remained cancer-free after 3 years.
After 3 years, 86.3% of patients who received immunotherapy were alive without the cancer coming back, compared with 76.2% of patients who received chemotherapy alone. - The difference was meaningful for patients.
In simple terms, about 10 more patients out of every 100 remained cancer-free at 3 years when immunotherapy was added. - Overall survival is still being followed.
It is too early to know whether this treatment helps patients live longer, but the early results are encouraging.
Key Takeaway Points
- Immunotherapy significantly reduced the risk of recurrence
The ATOMIC study showed that adding atezolizumab reduced the chance of the cancer returning by approximately 50%.
- MSI-high colon cancer may require a different treatment approach
These cancers are biologically different and may benefit from immunotherapy much earlier than previously thought.
- This study may eventually change the standard of care
While longer follow-up is still required, ATOMIC is one of the strongest studies to date supporting immunotherapy after surgery for Stage III MSI-high colon cancer.
Why Oncologists Are Excited About These Results
The ATOMIC study did not appear in isolation.
For several years, oncologists have observed remarkable responses to immunotherapy in patients with advanced MSI-high colon cancer.
The landmark KEYNOTE-177 study demonstrated that immunotherapy was superior to chemotherapy in many patients with metastatic MSI-high colorectal cancer.
At the same time, earlier research suggested that MSI-high tumours may derive less benefit from traditional fluorouracil-based chemotherapy compared with other colon cancers.
Taken together, these findings created an important question:
Could immunotherapy work even better if given before recurrence occurs?
The ATOMIC study provides some of the strongest evidence yet that the answer may be yes.
Australian Perspective
At the time of writing, atezolizumab is not PBS-funded for Stage III MSI-high colon cancer, and this treatment is not currently considered routine Australian practice.
Access may vary depending on:
- Clinical trial availability
- Regulatory approvals
- Individual funding arrangements
- Future PBS decisions
Treatment recommendations should always be individualised and discussed with your treating oncologist.
My Perspective
As a medical oncologist and cancer genetics physician, I see the ATOMIC study as an important step forward.
For many years, immunotherapy has helped patients with advanced MSI-high colon cancer.
The important question was whether we could use immunotherapy earlier, after surgery, to reduce the chance of the cancer coming back.
The ATOMIC study suggests that this may be possible for some patients with stage III MSI-high colon cancer.
More follow-up is still needed.
However, for patients with Lynch syndrome, hereditary bowel cancer or MSI-high colon cancer, this is an important study to know about.
Bottom Line
If you have stage III colon cancer and your tumour is MSI-high or linked to Lynch syndrome, the ATOMIC study is important.
The study showed that adding immunotherapy after surgery and chemotherapy may reduce the chance of the cancer coming back in selected patients.
In the future, immunotherapy may become part of standard treatment for some patients with stage III MSI-high colon cancer.
However, this treatment is not right for everyone.
Treatment decisions should always be discussed with an experienced medical oncologist.
References
- Sinicrope FA, Ou FS, Arnold D, et al. Atezolizumab plus FOLFOX for stage III mismatch repair-deficient colon cancer. N Engl J Med. 2026;394(12):1155-1166. doi:10.1056/NEJMoa2507874
- André T, Shiu KK, Kim TW, et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med. 2020;383(23):2207-2218. doi:10.1056/NEJMoa2017699
- Ribic CM, Sargent DJ, Moore MJ, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003;349(3):247-257. doi:10.1056/NEJMoa022289
- Sargent DJ, Marsoni S, Monges G, et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol. 2010;28(20):3219-3226. doi:10.1200/JCO.2009.27.1825
Frequently Asked Questions (FAQ)
- What is MSI-high colon cancer?
MSI-high colon cancer is a subtype of bowel cancer that has difficulty repairing damaged DNA. These cancers often respond differently to treatment and may be particularly sensitive to immunotherapy.
- Does MSI-high mean I have Lynch syndrome?
Not necessarily.
Some MSI-high cancers are caused by Lynch syndrome, while others occur sporadically. Additional testing is usually required.
- Is immunotherapy currently standard treatment after surgery?
Not at present in Australia. However, studies such as ATOMIC may influence future treatment guidelines.
- Should family members be tested?
If Lynch syndrome is suspected or confirmed, family members may benefit from genetic counselling and testing.
- Should I seek a second opinion?
Many patients with MSI-high colon cancer or Lynch syndrome seek a second opinion because treatment recommendations continue to evolve rapidly.
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)