Treatment Options for Colorectal Cancer

Surgery is the most common initial treatment used in all stages of colorectal cancer. The goal is to remove the tumor through one of three methods of surgery:

• Local excision: This procedure is most successful as a singular treatment in the early stage of colorectal cancer. Doctors insert a small cutting tool through the rectum and into the colon to cut out (excise) the tumor. In stages 0 and 1, this may be the only treatment needed.
• Colon resection with anastomosis: This surgery addresses larger tumors. It removes the cancerous part of the colon and some nearby healthy tissue and then connects the cut ends of the colon. Lymph nodes may also be removed and examined for cancerous tissue.
• Colon resection with colostomy: This procedure is used in more advanced cancers or if the colon is too damaged to be sewn back together. Here, the colon is essentially rerouted to a stoma (an opening) outside the abdominal wall where waste can pass through. A bag is put in place to collect the waste. This procedure is called a colostomy, and it can be either temporary or permanent, depending on how much of the colon needs to be removed.

Chemotherapy or radiation treatments are commonly used after surgery to kill off any remaining cancer cells. This post-surgical treatment — called adjuvant therapy — reduces the risk of cancer returning.

Surgery plus chemotherapy as adjuvant therapy is the treatment standard for colorectal cancers in stage 3 and beyond.

Chemotherapy uses specific drugs to stop the growth of cancer cells. Depending on the cancer’s stage, chemotherapy is often recommended before or after surgery to eliminate or reduce cancer cells.

While it’s possible that cancers in stage 0 or 1 may not need chemotherapy, cancers in stage 2 and higher often require it to help prevent the cancer from returning.

The specific type of chemotherapy used is determined by the cancer’s stage and location. Chemotherapy treatment often involves side effects, which vary depending on the type of medications used.

Common side effects of chemotherapy include:

• nausea and vomiting
• mouth sores
• weight loss or loss of appetite
• diarrhea
• skin and nail changes
• hair thinning

Additional chemotherapy side effects may differ based on the method and specific medications used.

Radiation therapy uses high energy X-rays or other types of radiation to kill or contain cancer cells. The type of radiation given depends on the cancer’s stage, but there are two general types of radiation therapy:

• External radiation: External radiation uses an outside machine to send radiation into the body aimed at the cancer areas. This kind of radiation is more often used to relieve symptoms and improve quality of life for people with advanced cancer.
• Internal radiation: This radiation strategy places a radioactive substance directly in contact with the cancer cells. It’s delivered into the body using catheters, seeds, wires or needles.

Radiation therapy is often used combined with chemotherapy in more advanced stages of colorectal cancers.

Ablation therapy is a minimally invasive procedure that uses heat or extreme cold to destroy abnormal or cancerous tissues. Doctors typically use the following types of ablation therapies for colorectal cancer:

• Radiofrequency ablation: This procedure uses a special probe with small electrodes to destroy localized cancer cells. The probe can either be inserted directly through the skin or through an abdominal incision. Radio waves are sent through the probe to create a current that heats and destroys the desired area.
• Cryosurgery: Cryosurgery uses extremely cold gas to destroy cancer cells. The process is similar to radiofrequency ablation, where an inserted probe delivers a freezing gas that kills cancer cells.

Radiofrequency ablation and cryosurgery are primarily used to treat unresectable advanced colorectal cancer that has spread to the liver. These procedures are typically used with other treatments, not as a standalone treatment.

Side effects of ablation procedures include:

• liver infection
• abdominal pain
• fever
• bleeding into the chest or abdominal cavities
• abnormal liver tests

Targeted therapy uses drugs or other substances to locate and attack specific cancer cells. This kind of treatment is currently limited to people with stage 4 metastatic colorectal cancer. These therapies sometimes work when chemo drugs don’t and may have different side effects.

The types of targeted therapy most used in colorectal cancer treatment include:

• Monoclonal antibodies: These lab-made immune system proteins are engineered to destroy cancer cells. The antibodies attach to a specific target on cancer cells and can then either kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion, either alone or in combination with other treatments. There are different types of monoclonal therapies:
  • Vascular endothelial growth factor (VEGF) inhibitor therapy: This therapy stops new blood vessels from forming, depriving and killing cancer cells that rely on new blood vessels. VEGF inhibitor therapy does this by blocking VEGF. VEGF is a substance made by cancer cells that causes new blood vessels to form. Common VEGF inhibitor drugs include bevacizumab (Avastin) and ramucirumab (Cyramza).
  • Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFR inhibitor therapy stops the cancer cells from growing and dividing. It does this by preventing a protein called epidermal growth factor from finding its attachment to the cancer cell. If the protein cannot attach, then the cancer cell cannot grow. Common EGFR inhibitor drugs include cetuximab (Erbitux) and panitumumab (Vectibix).
• Protein kinase inhibitor therapy: This therapy blocks a protein that’s needed for cancer cells to divide and multiply. This includes BRAF inhibitors that block the activity of proteins made by abnormal BRAF genes.
• Angiogenesis inhibitors: These drugs stop the growth of new blood vessels, which prevents tumor growth. ziv-aflibercept (Zaltrap) and regorafenib (Stivarga) are two angiogenesis inhibitors that can stop or prevent new blood vessel formation.

Immunotherapy is a type of biologic therapy that uses your immune system to fight cancer. It uses proteins called “checkpoints” on immune system cells that need to be activated or turned “off” to start an immune response. Colorectal cancer cells may use these checkpoints to avoid an attack by the immune system.

Immunotherapy drugs that target these checkpoints are called “checkpoint inhibitors.” They help restore an immune system response against cancerous cells. They may be used in people whose colorectal cancer cells are positive for specific gene changes, and whose cancer cannot be surgically removed, has come back, or has spread to other parts of the body.

There are two types of checkpoint inhibitors used in advanced stage colorectal cancer:

• PD-1 Inhibitor: These are drugs that target checkpoint proteins called PD-L1 on cancer cells and PD-1 found on immune system T cells. In colorectal cancer, if PD-L1 is able to bind with PD-1, they can stop the T cell from killing tumor cells. PD-1 inhibitors stop these proteins from binding, so the T cells are able to destroy tumor cells. Two PD-1 inhibitor drugs are:
  • Pembrolizumab (Keytruda): This drug can be used to treat advanced or metastatic colorectal cancer. It’s given as an intravenous infusion every 3 or 6 weeks.
  • Nivolumab (Opdivo): This drug can be used alone or with other medications for people whose metastatic colorectal cancer has continued to grow after chemotherapy treatment. As a standalone medication, it’s usually given as an intravenous infusion every 2 or 4 weeks.
• CTLA-4 Inhibitor: These drugs also boost the immune response, but block a different T cell protein, CTLA-4, which normally helps keep the immune response in check. Ipilimumab (Yervoy) is a CTLA-4 inhibitor, that’s used along with nivolumab (Opdivo) for colorectal cancer. It’s given as an IV infusion every 3 weeks for four treatments.

It’s possible to have an infusion reaction while receiving these drugs. The response may be similar to an allergic reaction. Additionally, standard side effects of immunotherapy include:

• nausea
• cough
• joint pain
• itching and skin rash
• fatigue
• loss of appetite
• constipation
• diarrhea

Immunotherapy drugs work by improving the immune system’s ability to see and attack cancer cells. However, it’s possible that the immune system may attack other body areas causing serious issues in certain organs or other body systems. For this reason, it’s important to be monitored closely while undergoing immunotherapy in the event of any adverse reactions.

While surgery remains the most common initial treatment for many stages of colorectal cancer, emerging new therapies and clinical trials continue to be researched. Some of these include:

• Combination therapies: The COMMIT clinical trial is studying the effectiveness of a combination of chemotherapy, bevacizumab (Avastin) and/or atezolizumab (Tecentriq) in treating metastatic colorectal cancers in people with DNA mismatch repair deficiency.
• Targeted therapies: A key research area for people with metastatic colorectal cancer is the use of targeted therapies against gene mutations that may drive tumor growth. The hope is to find agents that can block the activity of abnormal proteins made by these mutations. Some trials and recent FDA approvals include the MOUNTAINEER clinical trial, which recently received FDA approval, the FDA approval of Braftovi, and an NCI sponsored trial focused on combination therapies.

The outlook and overall survival rate is greatly dependent on the stage of the cancer at diagnosis, a person’s response to treatment, and their overall health. Early diagnosis and timely screenings are the most important factors in treating colorectal cancer before it advances.

Here are the 5-year relative survival rates for colon and rectal cancers according to the SEER database. Percentages are based on people who receive a diagnosis of cancers of the colon in the United States between 2012 and 2018.

It’s important to note that these numbers apply only to the stage of the cancer when it’s first diagnosed. They don’t apply to cancers that continue to grow, spread, or come back after treatment.

Doctors can choose from a number of treatment options for colorectal cancer, and more treatments are actively in development.

While early diagnosis and treatment offer the best outlook for a full recovery, strong treatment options are in place for more advanced colorectal cancer.

It’s important that you work closely with your doctor to explore all your treatment options and what they may involve. Be sure to ask about clinical trials and emerging treatments if you need additional avenues.

Colorectal cancer treatment continues to develop, improving your overall outlook.