Metastatic Colorectal Cancer: What to Ask

This page is for people with metastatic (stage IV) colorectal cancer and the people close to them. It explains the terms you may hear and the questions worth asking your care team, based on National Cancer Institute (NCI) information.

Cetuximab and panitumumab block a receptor called EGFR. They only work if the pathway below that receptor is normal.

NCI is explicit. Tumors with KRAS variants are not sensitive to cetuximab. Adding cetuximab helps survival in colon cancers that lack a KRAS variant.

There is a warning attached. NCI notes that people with KRAS-altered tumors may do worse when cetuximab is added to chemotherapy containing bevacizumab.

So KRAS testing matters before those drugs are used, and it is worth asking for by name. Other tests may be run too, such as BRAF and mismatch repair. Ask what tests were sent and what came back.

NCI lists targeted therapy with encorafenib and cetuximab for patients with a BRAF V600E change.

Where it fits in your treatment is a decision for your oncologist. Ask whether your tumor was tested, and if the change is there, where in the plan this combination would come.

About 4% of stage IV colorectal cancers are mismatch repair deficient, also written dMMR or MSI-high.

NCI explains that this can be tested by looking for lost mismatch repair proteins. Since 2015 it has also predicted response to checkpoint drugs.

Pembrolizumab was approved in 2020 for untreated metastatic dMMR or MSI-high colorectal cancer. If you are in that group, the first treatment may not be chemotherapy at all.

MSI-high is also the main pattern seen in Lynch syndrome. A positive result matters to your relatives.

NCI treats liver-only disease as a distinct situation.

Its list includes chemotherapy before surgery to shrink the tumor, surgery to remove part of the liver, and radiofrequency ablation or cryosurgery for people who cannot have surgery.

Ask whether a liver surgeon should look at your scans.

• Has my tumor been tested for KRAS and NRAS variants, and what did they show?
• Is there a BRAF V600E change, and does encorafenib with cetuximab apply?
• Is my tumor mismatch repair deficient or MSI-high?
• If it is, should immunotherapy come before chemotherapy?
• My spread is liver only. Can a liver surgeon review my scans now?
• Which chemotherapy backbone are you choosing, and would bevacizumab be added?
• How will you monitor my hands and feet on oxaliplatin, and what would make you change the dose or pause it?

This is one of the clearest trade-offs in colorectal cancer.

The clearest figures come from the pooled IDEA analysis NCI cites, which studied stage III disease after surgery rather than metastatic disease. Nerve damage of grade 2 or worse affected 16.6% of people given 3 months of FOLFOX, against 47.7% given 6 months. With CAPOX the figures were 14.2% and 44.9%. The length of treatment, not the drug alone, drove the difference.

Those figures come from adjuvant treatment after surgery for stage III disease, where the course has a planned end date. Metastatic treatment does not work that way, so these figures cannot set your own stopping point. What they do show is that nerve damage was more common with longer treatment. So before you start, ask:

• How your hands and feet will be checked
• How to report changes
• What would prompt a dose change or a break

That conversation belongs at the beginning, not after your fingers go numb.

• Call your cancer team at once if you measure 100.4°F (38°C) or higher, or get shaking chills, at any point while you are on chemotherapy. CDC treats a fever during chemotherapy as a medical emergency. Ring them day or night. If you cannot reach them quickly, go to an emergency department and say at the desk that you are having chemotherapy. Go to an emergency department too if you have severe cramping belly pain with vomiting and no gas or stool passing, which can mean the bowel is blocked, for sudden severe belly pain with a hard, tender abdomen, for heavy rectal bleeding with dizziness or fainting, or for a rash with wheezing, throat tightness or faintness during a cetuximab or panitumumab infusion.
• Call 911 or go to an emergency department if chest pain or breathlessness starts while you are on immunotherapy. NCI lists inflammation of the heart muscle and of the lungs among the rarer effects of these drugs, and both are assessed straight away rather than later in the day. Do not drive yourself.
• Call your care team right away if diarrhea will not stop or you cannot keep fluids down, which matters most on irinotecan. Call right away too for new yellowing of the eyes or skin, and for a new cough while you are on immunotherapy.
• Call your care team within a day or two if numbness or tingling in your hands or feet is new or getting worse. On oxaliplatin, the plan may be changed. Do the same for a rash that is spreading or sore, and for home blood pressure readings running high. If mouth sores stop you eating or drinking, call right away.

Related: Cancer Staging, Biomarker Testing, Clinical Trial vs Standard Treatment, and Palliative Care.

• NCI PDQ - Colon Cancer Treatment (Patient Version)
• NCI PDQ - Colon Cancer Treatment (Health Professional Version)
• NCI PDQ - Rectal Cancer Treatment (Patient Version)
• NCI PDQ - Gastrointestinal Complications (Health Professional Version)
• NCI - Infection and Neutropenia During Cancer Treatment
• CDC - Watch Out for Fever (Preventing Infections in Cancer Patients)