MSI-high or dMMR colorectal cancer: choosing immunotherapy

What the two terms tell you

Mismatch repair is one of the systems that corrects errors when DNA is copied. A tumor described as deficient mismatch repair, or dMMR, has lost effective repair through that system. MSI-high refers to a pattern of DNA instability that often accompanies it.

Protein staining can assess mismatch repair proteins, while DNA-based tests can assess MSI. The words on the report may therefore differ even when they point toward a similar treatment discussion. Ask the team to confirm the final interpretation, especially if two tests disagree or the available tissue was limited.

Sources and references: [1] [2]

Separate advanced disease from a localized tumor

In metastatic or unresectable colorectal cancer, MSI-H or dMMR can lead directly to a discussion about checkpoint inhibitors. If the tumor is localized and removable, the decision also involves the operation, recurrence risk and the evidence for treatment before or after surgery.

For rectal cancer, an immune-based approach in selected dMMR disease can raise organ-preservation questions. Those decisions require specialist assessment and a follow-up program. Do not transfer a treatment plan from metastatic colon cancer to an early rectal tumor simply because the biomarker is the same.

Sources and references: [1] [3]

Which immune-treatment options may be compared?

Pembrolizumab is an established option for MSI-H or dMMR advanced colorectal cancer in appropriate settings. Nivolumab with ipilimumab received US FDA approval in April 2025 for unresectable or metastatic MSI-H or dMMR colorectal cancer in adults and patients aged 12 years or older.

The team should compare the applicable regimens, previous treatment, anticipated benefit and toxicity. More immune drugs can mean more immune-related side effects. Ask why one regimen is preferred for your cancer burden and health, and how its local indication applies if care is planned in China.

Sources and references: [1] [4]

Health history can change the recommendation

Tell the oncologist about inflammatory bowel disease, lupus or another autoimmune condition, previous organ transplantation and medicines that suppress the immune system. These factors can complicate checkpoint-inhibitor treatment and deserve discussion before the first dose.

Recent infections, liver problems and ongoing symptoms also need to be documented. If you already have diarrhea or breathlessness, recording the baseline helps the team interpret changes after treatment. Bring your full medicine list, including steroids prescribed for another condition.

Sources and references: [5]

Know how the team will assess response

Monitoring combines symptoms, examination, scans and laboratory results. Ask when the first response scan is planned and what would prompt earlier assessment. Feeling better is valuable, but it is only one part of the review.

Sometimes imaging changes during immunotherapy need additional interpretation. Worsening symptoms should be assessed promptly rather than assumed to be a harmless immune response. If progression is suspected, the team will weigh repeat assessment against switching treatment or addressing a dangerous local problem.

Sources and references: [5] [1]

Recognize symptoms that need a call

Checkpoint inhibitors can inflame organs such as the bowel, lungs, liver or endocrine glands. New persistent diarrhea, shortness of breath, a worsening cough, jaundice or unusual exhaustion should reach the treating team promptly. Severe symptoms require urgent medical assessment.

Immune effects may occur during treatment or after it has stopped. Carry the name of the drug and the oncology contact details when traveling. Ask who can arrange tests and prescribe treatment for a suspected immune complication if you are far from the infusion center.

Sources and references: [5]

Ask whether the result has implications for relatives

An MSI-H or dMMR result may prompt evaluation for Lynch syndrome. The next step is to distinguish an inherited change from one that arose only in the tumor. The affected proteins, further tumor testing and family history help guide the next step.

Ask whether genetic counseling or a germline blood or saliva test is appropriate. This is a separate question from whether immunotherapy fits the cancer. If an inherited syndrome is confirmed, relatives may benefit from a structured discussion about testing and screening.

Sources and references: [1]

Make the consultation specific to the decision

For a Shanghai review, bring the MSI/MMR report, pathology and current scans to a colorectal cancer service such as the one described in our Fudan Cancer Center profile.

EastMedGo can help coordinate a records-based inquiry about treatment selection or an organ-preservation assessment. Through contact, tell us whether the disease is localized or metastatic and whether you have already received an immune drug. We can help clarify the appropriate appointment and the practical requirements for an in-person review.

Sources and references: [6]

Common questions