Treatments for Colorectal Cancer

How do doctors decide on a treatment plan?

Doctors base their treatment recommendations on several factors, including:

• the stage of your cancer
• the subtype based on pathology
• additional test results, including biomarkers
• how fast the cancer is growing or how likely it is to spread
• whether the cancer is newly-diagnosed or has recurred after one or more treatments
• your overall health

Make sure that you receive a copy of your records. Ask your doctor to explain your diagnosis, test results, pathology report, stage, prognosis and treatment recommendations in terms that you can understand. This will allow you to work with your doctor to choose a treatment plan that is right for you. 

Most colorectal cancer is treated with one or more of the following treatments. Every treatment has potential risks and side effects. Before any new treatment or surgery, make sure your healthcare team tells you about what to expect.

Surgery

Treatment for colorectal cancer typically involves surgery. 

Early-stage colorectal cancer

Surgery for early-stage colorectal cancer may include: 

• Polypectomy (polyp removal) is used to completely remove small cancers contained within a polyp during a colonoscopy.
• Endoscopic mucosal resection (removing polyps and surrounding tissue) allows doctors to remove larger polyps and a small amount of lining of the colon during a colonoscopy.
• Minimally invasive or laparoscopic surgery is used to remove polyps that cannot be removed during a colonoscopy. During laparoscopic surgery, small incisions are made in the abdominal wall so that the surgeone can insert cameras to help see the colon and instruments to help remove the cancer. Polyps are removed as well as a part the part of the colon that contains the polyp, and nearby lymph nodes through these incisions.

More advanced cancer

Surgery for more advanced colon cancer may include partial colectomy to remove the part of the colon that contains the cancer and normal tissue on either side of the cancer. A partial colectomy can often be done using a laparoscope, but sometimes open abdominal surgery is required.

Often, after removing the cancer, the surgeon can reconnect the healthy portions of the colon. When it is not possible to reconnect the healthy portions of the colon, the surgeon creates a hole in the wall of the abdomen called an ostomy. Ostomies allow stool to be removed from the body into a bag that fits securely over the opening. Sometimes the ostomy is only temporary, and after time the ostomy can be reversed.  However, in some cases it may be permanent.

Very advanced cancer

• If the cancer has spread only to the liver or lung, doctors may recommend surgery in combination with other treatments such as chemotherapy.
• For people with very advanced cancer or overall poor health, surgery may be used only to relieve a blockage of the colon or to improve symptoms such as bleeding or pain.

Considerations for people with inherited mutations

For people who have an inherited mutation linked to very high risk for colorectal cancer, more extensive colectomy surgery may be recommended to treat their cancer and prevent new cancers from developing. These surgeries include: 

• Total proctocolectomy with Ileal Pouch and Anal Anastomosis (TPC IPAA) involves removal of the colon and rectum but spares the anal sphincter. People who have this surgery may remain continent and are able to control bowel movements. The surgeon uses a portion of the small intestine to create an internal pouch, which stores waste until a bowel movement. 
• Total abdominal colectomy with ileorectal anastomosis (TAC IRA) involves removal of the entire colon but spares the rectum. Not all people are candidates for this surgery, which leaves the risk for rectal cancers. 
• Total proctocolectomy with permanent end ileostomy (TPC EI) removes the entire colon, rectum and anus and creates an ostomy opening at the end of the small intestine. 

Chemotherapy

Chemotherapy for colon cancer is usually given after surgery if the cancer is has spread to deeper layers of the colon wall or has spread to the lymph nodes. Neoadjuvant chemotherapy may also be used before surgery to shrink a large cancer so that it is easier to remove with surgery.

Chemotherapy for colon cancer is usually a combination of two or three chemotherapy drugs.  The most common chemotherapies are:

• 5-FU: 5-flourouracil
• Capecitabine, also known as Xeloda, an oral form of 5-fluoruracil
• Irinotecan (Camptosar)
• Oxaliplatin (Eloxatin)

Radiation therapy

Radiation therapy is used more often to treat rectal and anal cancers than colon cancer. It also may be used as part of some clinical trials.

How is immunotherapy used in colorectal cancer?

Immunotherapies are cancer treatments that help the body’s immune system detect and attack cancer cells.

Immune checkpoint inhibitors are a type of immunotherapy used to treat several different  cancers, including colorectal cancer. Some cancer cells can switch off the immune system. Immune checkpoint inhibitors prevent this from happening. This allows the immune system to find, unmask and destroy cancer cells.

Other names for these drugs are:

• PD-1/PD-L1 inhibitors
• PD-1/PD-L1-directed therapies

Immune checkpoint inhibitors work particularly well for treating cancers with the following biomarkers:  

• MSI-H (microsatellite instability-high), dMMR and MMR-d (mismatch repair deficiency); these biomarkers are common in people with Lynch syndrome
• POLE or POLD1 mutations
• TMB-High (tumor mutational burden-high)

See the tables below for a list of immunotherapies used to treat colorectal cancer.

See our general section on immunotherapy for more information on different types of immunotherapy, how they work and their possible side effects. 

Which immunotherapies are used for colorectal cancer?  

The immunotherapies used for colorectal cancer are:

• Jemperli (dostarlimab) - given as an intravenous injection (injected in the vein)
• Keytruda (pembrolizumab) - given as an intravenous injection (injected in the vein) or a subcuteous injection (injected under the skin)
• Opdivo (nivolumab) given as an intravenous injection (injected in the vein) or a subcuteous injection (injected under the skin)
• Yervoy (ipilimumab) - given as an intravenous injection (injected in the vein)

Stage 2 or stage 3 rectal cancers

• Jemperli may be used for early stage (stage 2 or stage 3) rectal cancer to shrink tumors before surgery. The use of dostarlimab in this setting is not yet FDA approved, and is considered off-label. However, the National Comprehensive Cancer Network (NCCN) expert panel for colorectal cancer has added this indication to their treatment guidelines.

Metastatic colorectal cancer

• Keytruda is approved for the treatment of unresectable or metastatic MSI-H or dMMR colorectal cancer. This approval includes first-line therapy (for people who have not received treatment in the metastatic setting) and treatment for people whose cancer didn't respond, came back or got worse after other treatments.  
• Opdivo (IV) and Yervoy in combination are approved for the first-line treatment of metastatic or unresectable MSI-H or dMMR colorectal cancer. 
• Opdivo (IV) and Yervoy in combination are approved for the treatment of metastatic or unresectable MSI-H or dMMR colorectal cancer that got worse or came back after chemotherapy. 
• Opdivo (IV or SQ) is approved for treatment of metastatic or unresectable MSI-H or dMMR colorectal cancer that got worse or came back after chemotherapy. 

Metastatic cancers with limited treatment options

• Jemperli is approved for treating multiple types of cancer if they are metastatic, have few remaining treatment options, and have a biomarker known as dMMR or MMR-d.
• The immunotherapy Keytruda is approved for treating people with different types of cancer (including colorectal cancer) if it is metastatic, has few remaining treatment options, and has a biomarker called TMB-high. 

Researchers are studying new ways to use immunotherapies to treat colorectal cancer. See the research section below for more information. 

How is targeted therapy used in colorectal cancer?

Targeted therapy is a type of cancer treatment designed to attack or kill cancer cells, while sparing normal cells as much as possible. The targeted therapies used in colorectal cancer are designed to target abnormal proteins, receptors or genes that are found in colorectal cancer cells or the surrounding tissue. Most colorectal cancer targeted therapies are used for advanced or metastatic cancer. 

See below for more information on the different targeted therapies used to treat colorectal cancer. Tumor biomarker testing can help doctors identify the patients most likely to benefit from certain targeted therapies.

Also see our general section on targeted therapy for more information about the different types of targeted therapy drugs, their uses and side effects. 

Which targeted therapies are used for colorectal cancer?  

Several targeted therapies are used to treat advanced or metastatic colorectal cancer. Some require biomarker testing before they can be prescribed. 

Targeted therapies that do not require biomarker testing

Anti-VEGF therapies
These drugs block tumors from forming blood vessels. The following drugs do not require biomarker testing for use in treating colorectal cancer:

• Avastin (bevacizumab) 
• Cyramza (ramucirumab)
• Fruzaqla (fruquintinib)
• Zaltrap (ziv-aflibercept)

Stivarga (regorafenib)
Stivarga blocks several different types of proteins in the body that tumors use to grow. Stivarga may be used to treat metastatic colorectal cancer that has come back after treatment with other drugs.

Targeted therapies that require biomarker testing

BRAF V600E mutations
BRAF is a gene that helps control how cells grow and divide. A specific mutation called BRAF V600E can drive colorectal cancer growth and biomarker testing for this change is important because it identifies people who may benefit from targeted treatments designed specifically for this mutation. 

• Braftovi (encorafenib) may be used in combination with cetuximab for metastatic colorectal cancer with a BRAF V600E mutation, after prior therapy.
• Braftovi may be used in combination with cetuximab and fluorouracil-based chemotherapy for metastatic colorectal cancer with a BRAF V600E mutation.

RAS biomarkers (KRAS and NRAS)
KRAS and NRAS are part of a group of genes known as the RAS pathway. RAS genes  help control how cells grow and divide. Changes (mutations) in these genes are common in colorectal cancer and are important because they affect which targeted treatments are likely—or unlikely—to work.

RAS wild-type or RAS mutation negative and EGFR-positive
Colorectal cancers that do not have mutations in either KRAS or NRAS are called RAS wild‑type. People with RAS wild‑type tumors may benefit from some targeted therapies.

Targeted therapies called EGFR receptors (epidermal growth factor receptors) require biomarker testing. These drugs may be used for colorectal cancers that are negative for a KRAS and NRAS mutations and positive for a biomarker known as EGFR-positive. 

• Erbitux (cetuximab)
• Vectibix (panitumumab)

KRAS G12C mutation
KRAS G12C is one specific type of KRAS mutation. Cancers that have KRAS G12C can be directly targeted with certain newer drugs, making it an important biomarker to test for in people with metastatic colorectal cancer. These drugs are approved to treat: 

• Krazati (adagrasib) is used in combination with Erbitux for advanced or metastatic colorectal cancer that has been treated with chemotherapy.
• Lumakras (sotorasib) is used in combination with Vectibix for metastatic colorectal cancer that has been treated with chemotherapy. 

HER2-positive
Anti-HER2 therapies are used for people with advanced colorectal cancer when tumor testing shows a biomarker called HER2-positive. The drugs used to treat advanced colorectal cancer include:

• Enhertu (trastuzumab deruxtecan)
• Herceptin (trastuzumab)
• Tukysa (tucatinib)

Herceptin and Tukysa are approved for treating colorectal cancers that are RAS-negative (RAS wildtype). Enhertu is approved for treating colorectal cancers with or without RAS mutations. 

NTRK gene fusions
NTRK gene fusions are biomarkers that are rarely found in colorectal cancer. The following drugs may be used for different types of advanced cancers (including colorectal cancer) with NTRK gene fusions that have gotten worse, stopped responding or came back after other treatments.   

• Entrectinib (Rozlytrek)
• Repotrectinib (Augtyro)
• Vitrakvi (larotrectinib) 

RET gene fusions
RET gene fusions are biomarkers that are rarely found in colorectal cancer.   

• Retevmo (selpercatinib) is a targeted therapy that is used to treat advanced cancers with a rare mutation known as a RET gene fusion.

Targeted therapies for other biomarkers
Researchers are studying new ways to use targeted therapies to treat colorectal cancer. Many of these studies rely on the results of biomarker testing to determine eligibility. See the research section below for more information.

Treatment side effects

Your healthcare team should explain what you should expect from all treatments, including:

• all of the possible risks and side effects of each treatment.
• which side effects may be serious and how to tell. 
• when and who you should call if you experience a side effect.
• what can be done to treat or alleviate each side effect. 

Make sure you let your healthcare team know if you experience any side effects of your treatment. For more information about possible treatment side effects, see our section on Cancer Treatment by Treatment Type.