Stage IV Colorectal Cancer
Your treatment will be specialized depending on your specific circumstances, which include the organs your cancer has spread to, which biomarkers your cancer possesses, and what therapies you have already tried.
Take time to get the best information and advice possible from a multidisciplinary team. This process is vitally important. Make sure to get a second opinion, even if it takes extra time.
Biomarker Testing
All colorectal cancer stage 4 patients should undergo biomarker testing. Biomarkers are targetable features of a cancer, often mutations or changes in specific genes that can be targeted by specific drugs or therapies. Biomarker testing can give your treatment team a better idea of which therapies might work, and which therapies they should avoid.
All metastatic colorectal cancers should be tested for the following biomarkers at a minimum:
- Mismatch repair deficiency or microsatellite instability (dMMR/MSI-H)
- RAS mutations (KRAS or NRAS)
- BRAF mutations
- HER2 amplification
It is possible to test for many biomarkers at one time using a process called next generation sequencing (NGS). NGS can find some rare biomarkers that may have specific treatments available, such as:
- POLE/POLD1 mutations
- RET fusions
- NTRK fusions
- DPD deficiency testing, if receiving 5-FU or capecitabine
Surgery
If the liver, lungs, or the lining of the abdomen (peritoneum) are affected, you may undergo multiple surgeries to remove metastatic disease. Often, chemotherapy and radiation are combined with surgery to shrink tumors.
Partial hepatectomy
Pulmonary metastasectomy
Hyperthermic intraperitoneal chemotherapy
Cytoreductive surgery
Interventional radiology procedures
Ablation and chemoembolization are advanced interventional radiology techniques used to target and treat tumors.
- Ablation: is used to destroy small tumors on the liver or lungs. Ablation involves guiding a specialized needle or probe into or near the tumor and delivering targeted energy to the tumor, hopefully destroying it while avoiding damaging the surrounding tissues. Ablation may also be performed using targeted radiation, referred to as “ablative radiotherapy.”
- Chemoembolization: is sometimes called transarterial chemoembolization (TACE). It is a combination of an embolization procedure (a procedure that reduces blood flow to the liver) and chemotherapy.
Radiation therapy
Two advanced radiation therapy techniques used to treat colorectal cancer are:
- Stereotactic body radiation therapy (SBRT): is where high doses of radiation are directed at tumors in the body using very precise beams by an external machine. SBRT may be used to treat colorectal cancer that has spread to the lungs, liver, or bones.
- Selective internal radiation therapy (SIRT): is a procedure that delivers tiny radioactive beads directly to the tumor(s) in the liver. The beads are injected into blood vessels leading to the tumor, causing them to collect in the tumor and deliver radiation.
Chemotherapy combinations
There are a variety of chemotherapy combinations that may be prescribed.
CapeOx or Xelox
capecitabine (Xeloda®) plus oxaliplatin (Eloxatin®). Capecitabine is an oral drug that works the same way as 5-FU inside the cancer cell.
Folfox
5-FU, oxaliplatin (Eloxatin®), and leucovorin
These regimens may be combined with targeted therapies such as bevacizumab (Avastin®), cetuximab (Erbitux®), or panitumumab (Vectibix®).
Folfiri
5-FU, irinotecan (Camptosar®), and leucovorin
These regimens may be combined with targeted therapies such as bevacizumab (Avastin®), cetuximab (Erbitux®), or panitumumab (Vectibix®).
Folfirinox
includes leucovorin, 5-FU, irinotecan, and oxaliplatin. This may also be combined with the targeted therapy bevacizumab (Avastin®)
Other Options
Patients who are not able to tolerate intensive therapy have other options. Doctors may recommend:
- 5-FU plus leucovorin with or without bevacizumab (Avastin®)
- Capecitabine (Xeloda®) with or without bevacizumab (Avastin®) – treatment with capecitabine (Xeloda®) alone should only be considered a reasonable option for selected patients who are not candidates for more aggressive combination regimens with oxaliplatin (Eloxatin®) or irinotecan (Camptosar®).
Other options
Trifluridine and tipiracil (Lonsurf®)
Lonsurf is an oral therapy that may be used in metastatic (stage IV) colorectal cancer, with or without bevacizumab.
Liver Mets and HAI Pumps
No two patients are the same, and neither are their diagnoses. Treatment options vary depending on stage, prior therapy, and location of tumors, especially for stage IV patients. For CRC patients with metastatic disease, liver metastases are common and may be treated with a variety of specialized methods, one of which is Hepatic Artery Infusion (HAI) therapy. Join MSKCC medical oncologist Louise Connell and stage IV survivor Carole Motycka for an informative conversation about colorectal cancer, liver metastasis, and HAI pump therapy.
This webinar was sponsored by Intera Oncology (now part of Boston Scientific)
Unpacking Colorectal Cancer Metastases
Navigating colorectal cancer treatment can be overwhelming, especially when dealing with stage IV (metastatic) cancer. Join oncologist and Fight CRC board member Cathy Eng, MD and Fight CRC RATS manager and stage IV survivor Phuong Gallagher as they discuss common locations for CRC metastases, available treatment options, and answer your questions about stage IV colorectal cancer.
Targeted therapies
Targeted therapies are not chemotherapy, and work in different ways. They may work when chemotherapy doesn’t and may present different side effects. Targeted therapies may be used alone, with chemotherapy, or in combination with other targeted therapies. There are approved targeted therapies for colorectal cancer, including:
Cetuximab (Erbitux®)
Panitumumab (Vectibix®)
Bevacizumab (Avastin®)
Ziv-aflibercept (Zaltrap®)
Regorafenib (Stivarga®)
Ramucirumab (Cyramza®)
Vemurafenib (Zelboraf®)
Fruquitinib (Fruzaqla®)
Encorafenib (Braftovi®)
Approved as a first-line treatment in combination with cetuximab, 5-FU, leucovorin, and oxaliplatin in patients with metastatic colorectal cancer and a BRAF V600E mutation.
Trastuzumab (Herceptin® and others)
Pertuzumab (Perjeta®)
Tucatinib (Tukysa®)
Lapatinib (Tykerb®)
Fam-trastuzumab deruxtecan (Enhertu®)
Larotrectinib (Vitrakvi®)
Entrectinib (Rozlytrek®)
Selpercatinib (Retevmo®)
Adagrasib (Krazati®)
Sotorasib (Lumakras®)
Immunotherapies
Immunotherapy uses certain parts of a person’s immune system to fight disease. Immunotherapy for colorectal cancer has been shown to be effective in a small subset of patients with a certain biomarker, MSI, or dMMR.
Immunotherapy is only recommended if you haven’t already had treatment with a checkpoint inhibitor, such as pembrolizumab or nivolumab. All colorectal cancer patients of all stages should know their MSI/MMR status!
Pembrolizumab (Keytruda®)
is an option for patients who have the MSI-H or d-MMR biomarkers. This treatment is indicated for adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a MSI-H or dMMR biomarker, including patients with solid tumors that have progressed following prior treatment and who have no alternative treatment options.
Nivolumab (Opdivo®)
is for use in MSI-H or dMMR metastatic colorectal cancer. Nivolumab has been approved for metastatic colorectal cancer patients whose cancer either progressed after being treated with a fluoropyrimidine, oxaliplatin, and irinotecan, or did not respond to those treatments.
Ipilimumab (Yervoy®)
may be used in combination with nivolumab as a treatment option for metastatic colorectal cancer with MSI-H or dMMR cancer following the progression on a fluoropyrimidine, oxaliplatin, and irinotecan.
Dostarlimab (Jemperli®)
Colorectal cancer treatment by stage can be straightforward in the early stages, but it can become incredibly complicated once the cancer progresses. Your Guide in the Fight includes more detailed colorectal cancer treatment by stage for stages III and IV (recurrent) cancers.
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