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Stage 4 Colon Cancer


Patients diagnosed with Stage 4 colorectal cancer have disease that has spread from the colon or rectum to one or more distant sites in the body. Typical sites that colorectal cancer spreads to may include the liver, lungs, bones, distant lymph nodes or other sites.


Patients diagnosed with stage 4 colorectal cancer have an increasing number of treatment options as a result of genomic testing and the development of precision cancer medicines. Some patients may be cured of their cancer, and others can derive significant long-term survival benefit with appropriate sequencing of treatment based on their cancers genomic profile.


First Line Treatment of Metastatic Colon Cancer


Treatment of advanced colon cancer may consist of chemotherapy, precision cancer medicines, and immunotherapy or some combination that is often determined by genomic – biomarker testing of the cancer, surgery, and targeted therapies.


Fluorouracil chemotherapy (5-FU) has been the standard treatment for stage IV colon cancer and is typically administered with leucovorin (LV), a drug that is similar in structure and function to the essential vitamin folic acid.


The addition of other drugs to 5-FU/LV and an oral alternative has been found to provide additional benefit to 5-FU alone and standard chemotherapy treatment for advanced colon cancer now includes any of the following regimens for individuals that do not have a cancer driving mutation or targetable biomarker.


  • FOLFOX (LV/5-fluorouracil + Eloxatin (oxaliplatin)
  • CAPEOX (Xeloda (capecitabine) + Eloxatin)
  • FOLFIRI (LV/5-fluorouracil + Camptosar (irinotecan)
  • FOLFOXIRI (LV/5-fluorouracil + Camptosar + Eloxatin)


These treatment regimens typically paired with Avastin® (bevacizumab) are the standard initial treatment for most patients and improve survival particularly for the treatment of left sided colon cancers.


Colon Cancer Mutations Targeted by Precision Cancer Medicines


Genetic Mutations: Not all colon cancer cells are alike. They may differ from one another based on what genes have mutations. Molecular testing should be performed to test for genetic mutations or the proteins they produce on ALL patients. By testing an individual’s colon cancer for specific unique genomic- biomarkers doctors can offer a personalized treatment approach utilizing precision medicines. Colon cancer mutations are being identified and new medicines developed to target these mutations on an ongoing basis.


Individuals with the following biomarkers may have their colon cancer treated differently using targeted precision cancer medicines – other biomarkers are being identified on an ongoing basis.


Epidermal growth factor receptor (EGFR) occurs in ~ 10% of colon cancers.


BRAFV600: Patients with mutant BRAF genes generally have a poorer prognosis but may benefit from treatment with precision cancer medicines.


Microsatellite Instability High (MSI-H): MSI-H is a DNA abnormality found in about 15% of colon cancers.Keytruda, and Opdivo have both been demonstrated to improve treatment of individuals with MSI-High disease.


HER 2: Human epidermal growth factor receptor 2 (HER2) targeted therapies can dramatically improve outcomes HER2 + colon cancers and all colo-rectal cancers should be tested for HER 2.


NTRK:neurotrophic tropomyosin receptor kinases (NTRKs genes, which encode for TRKs can become abnormally fused to other genes, resulting in growth signals that can lead to cancer and be targeted with specific medications.


Maintenance Therapy


Maintenance therapy may improve survival for patients with metastatic colorectal cancer as compared with re-introduction of chemotherapy at the time of disease progression. Maintenance therapy refers to therapy that is used following initial systemic therapy, when a patient’s cancer is stable and not exhibiting signs of progression.


Possibilities to Improve Treatment


The major research focus in advanced colorectal cancer is the identification of additional cancer driving mutations as targets for precision cancer medicines and the development of immunotherapy treatment strategies.  Watch for clinical trials that may be beneficial.


Treatment of Colon Cancer That Has Metastasized to a Single Site


Many individuals with CRC involving the liver or other sites erroneously conclude that they have no treatment options other than systemic therapy. Stage 4 colorectal cancer commonly spreads to the liver or the lungs and patients who have cancer that has spread to one or two treatable sites are candidates for additional local treatment directed at the metastases. Clinical trials have demonstrated that the combination of systemic therapy and surgery for liver metastases further improves treatment outcomes. When it’s possible to completely surgically remove all liver metastases, surgery is a preferred treatment.


Although surgery offers some patients the chance for a cure many patients with liver metastases are not candidates for surgery because of the size or location of their tumors or their general health.


If the tumors cannot be removed surgically there are several other therapeutic options for the treatment of liver metastases, and isolated areas of cancer in other organs. The type of directed therapy used is determined by the size of the cancer, the number of metastases, and the location of the cancer within the liver or other organs.


Clinical Trials:


New anti-cancer therapies continue to be developed and evaluated in clinical trials. There are three phases of clinical trials before approval.  See our clinical trials section for more information.


Management of Liver Metastases


When colorectal cancer spreads to the liver, it doesn’t always cause symptoms. It may be picked up by liver function tests, which are blood tests that measure certain levels of enzymes and proteins in the blood. Abnormal levels can indicate liver disease or damage.


If liver metastasis causes symptoms, they can include:


• pain or discomfort in the mid-section

• fatigue and weakness

• weight loss/poor appetite

• fever

• bloating

• swelling in the legs

• a yellow tint to the skin or the whites of the eyes


In addition to liver function tests, doctors use imaging tests to diagnose liver metastases. These may include MRI (magnetic resonance imaging), CT scan (computed tomography), ultrasound, and/or PET scan (positron emission tomography). Sometimes, a combined PET/CT scan is used.


Your doctor also may recommend getting a sample of the suspicious area(s) for examination under a microscope (biopsy). He or she may involve an interventional radiologist to obtain precise and minimally invasive imaging.


The most common treatments for metastatic colorectal cancer in any location (bone, brain, lung, or liver) are systemic medications, which treat cancer throughout the entire body. Systemic medications include chemotherapy, hormonal therapy, and targeted therapies that have already been discussed.  Liver directed therapies, including surgery, may be an option.


Liver Directed Therapies:  There are numerous liver directed therapies available for those who are faced with a Stage 4 colorectal cancer diagnosis with liver metastases or colorectal cancer that has spread to the liver.  These therapies are dependent on the size, number, and location of the liver tumors. These liver directed therapies may include chemoembolization, cryoablation, cyberknife, hepatic arterial infusion, liver resection, liver transplant, proton beam therapy, radioembolization or SIRT, radiofrequency ablation, or SBRT.  You can learn more on our treatment page under liver directed therapies.





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