Who This Is For
Lynch syndrome colon cancer is different from many other bowel cancers because it may respond strongly to immunotherapy.
“ Your doctor has also mentioned MSI-high or dMMR cancer. You may be wondering what this means for your treatment.”
This article is for people with:
- Lynch syndrome
- Colon cancer
- MSI-high or dMMR colon cancer
- Locally advanced colon cancer
- Patients considering treatment before surgery
- Patients seeking a colon cancer second opinion
Why This Matters
Lynch syndrome is not only important because it increases the risk of bowel cancer.
It is also important because many Lynch syndrome-associated bowel cancers are MSI-high or dMMR.
These cancers have difficulty repairing DNA damage.
Because of this, they often contain many genetic errors.
The immune system may be able to recognise these cancers more easily than some other bowel cancers.
That is one reason immunotherapy can be so effective in selected patients.
In simple terms, Lynch syndrome can affect both cancer risk and treatment options.
A Clinical Observation
I recently met a 36-year-old man who had just been diagnosed with colon cancer.
He had never heard of Lynch syndrome.
There was no strong family history of cancer. In fact, he was the first person in the family to receive a diagnosis.
Unfortunately, this is more common than many people realise.
By the time we met, the cancer appeared locally advanced. The scans showed a large tumour and multiple enlarged lymph nodes. Naturally, his first question was:
“What are my treatment options?”
For many years, the answer would have been relatively straightforward. Surgery, chemotherapy, and sometimes additional treatment afterwards.
Today, however, some patients with Lynch syndrome may have another option.
Immunotherapy has completely changed the outlook for certain bowel cancers, and one study in particular caught the attention of cancer specialists around the world.
It was called the NICHE study.
Lynch Syndrome Colon Cancer: Why Is It Different?
Lynch syndrome is an inherited condition that increases the risk of several cancers, particularly bowel cancer.
The important point is not simply that Lynch syndrome increases cancer risk.
The important point is that many Lynch-associated cancers are highly visible to the immune system.
That makes them particularly sensitive to immunotherapy.
In some patients, the responses can be dramatic.
What Was the NICHE Study?
The NICHE study asked a simple question:
Could immunotherapy work better if it were given before surgery?
Traditionally, colon cancer is removed first.
However, researchers wondered whether the immune system might respond more strongly while the tumour was still present.
The idea was simple.
If the tumour is still there, the immune system has a clearer target to recognise and attack.
Study Design
The original NICHE study included 40 patients.
Patients received a short course of immunotherapy before surgery:
- One dose of ipilimumab
- Two doses of nivolumab
There was no traditional control group.
The researchers compared the results with what would usually be expected from standard treatment.
Key Results
- Most MSI-high or dMMR cancers responded strongly.
Almost every patient with an MSI-high or dMMR tumour had a response to immunotherapy. - Some patients had no living cancer cells left at surgery.
In the original NICHE study, around 60% of patients with dMMR tumours had no detectable living cancer cells left in the surgical specimen. - NICHE-2 confirmed very high response rates.
NICHE-2 focused on locally advanced, non-metastatic dMMR colon cancer and again showed very high response rates with immunotherapy before surgery. - The response was much stronger in dMMR cancers.
A small number of patients with MMR-proficient tumours also responded, but the benefit was much less pronounced.
What Do These Results Mean for Patients?
These results do not mean that every patient with colon cancer should receive immunotherapy before surgery.
The most important message is that MSI-high and dMMR colon cancers behave differently.
For patients with Lynch syndrome or MSI-high colon cancer, immunotherapy may open the door to different treatment discussions.
In selected patients, it may help shrink the cancer dramatically before surgery.
However, this approach is still specialised and should be discussed with an oncologist experienced in colorectal cancer, immunotherapy and cancer genetics.
For now, the key message is simple:
Every colon cancer should be tested for MSI or mismatch repair status, because that result may change both treatment decisions and family risk assessment.
Why Might Immunotherapy Work Better Before Surgery?
We have seen similar findings in other cancers.
One example is triple-negative breast cancer.
Studies showed that giving immunotherapy before surgery was more effective than waiting until after surgery.
The explanation may be simple.
The immune system learns by seeing the cancer.
When the tumour is still present, there is more information for the immune system to recognise and attack.
Once the tumour has been removed, some of that opportunity may be lost.
Overall, Lynch syndrome colon cancer is an area where treatment is changing quickly, especially as immunotherapy research continues to develop.
Key Takeaways
- Every Colon Cancer Should Be Tested
Testing for Lynch syndrome and MSI status is now essential.
- Lynch Syndrome Can Change Treatment Options
The results may open the door to immunotherapy.
- Some Patients Experience Remarkable Responses
In selected patients, immunotherapy can dramatically shrink or even eliminate visible cancer before surgery.
- Timing May Matter
Giving immunotherapy before surgery may be more effective than giving it afterwards.
- Research Is Moving Quickly
The way we treat bowel cancer today is very different from how we treated it only a few years ago.
My Clinical Perspective
The excellent responses seen in Lynch syndrome patients are no longer surprising to most cancer specialists.
What surprised me about the NICHE study was that some patients outside the traditional Lynch syndrome group also appeared to benefit.
That observation suggests we still have much to learn about how the immune system interacts with cancer.
For patients diagnosed today, that is encouraging news.
The treatment options available in 2026 are far more sophisticated than those available even a decade ago.
References
- Idos G, Valle L. Lynch Syndrome. In: Adam MP, Feldman J, Mirzaa GM, et al, eds. GeneReviews®. University of Washington, Seattle; 2004. Updated February 4, 2021. Accessed June 18, 2026. https://www.ncbi.nlm.nih.gov/books/NBK1211/
- Evaluation of Genomic Applications in Practice and Prevention Working Group. Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Genet Med. 2009;11(1):35-41. doi:10.1097/GIM.0b013e31818fa2ff https://pubmed.ncbi.nlm.nih.gov/19125126/
- Chalabi M, Fanchi LF, Dijkstra KK, et al. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med. 2020;26(4):566-576. doi:10.1038/s41591-020-0805-8 https://www.nature.com/articles/s41591-020-0805-8
- Chalabi M, Verschoor YL, Batista Tan P, et al. Neoadjuvant immunotherapy in locally advanced mismatch repair-deficient colon cancer. N Engl J Med. 2024;390(21):1949-1958. doi:10.1056/NEJMoa2400634 https://www.nejm.org/doi/full/10.1056/NEJMoa2400634
Frequently Asked Questions (FAQs)
- Is Lynch syndrome hereditary?
Yes. Lynch syndrome is usually inherited, and family members may also require testing.
- Does every Lynch syndrome patient need immunotherapy?
No. Treatment depends on the stage of the cancer and individual circumstances.
- Can immunotherapy replace surgery?
Not routinely. Surgery remains a critical treatment for most patients.
- Should I have genetic testing?
If Lynch syndrome is suspected, genetic testing is strongly recommended.
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)