Treatment of Colon Cancer, by Stage

Treatment for colon cancer is based largely on the stage (extent) of the cancer, but other factors can also be important.

People with colon cancers that have not spread to distant sites usually have surgery as the main or first treatment. Chemotherapy may also be used after surgery (called adjuvant treatment). Most adjuvant treatment is given for about 3 to 6 months.

Treating stage 0 colon cancer

Since stage 0 colon cancers have not grown beyond the inner lining of the colon, surgery to take out the cancer is often the only treatment needed. In most cases, this can be done by removing the polyp or taking out the area with cancer through a colonoscope (local excision). Removing part of the colon (partial colectomy) may be needed if a cancer is too big to be removed by local excision.

Treating stage I colon cancer

Stage I colon cancers have grown deeper into the layers of the colon wall, but they have not spread outside the colon wall itself or into the nearby lymph nodes.

Stage I includes cancers that were part of a polyp. If the polyp is removed completely during colonoscopy, with no cancer cells at the edges (margins) of the removed piece, no other treatment may be needed.

If the cancer in the polyp is high grade, or there are cancer cells at the edges of the polyp, more surgery might be recommended. You might also be advised to have more surgery if the polyp couldn’t be removed completely or if it had to be removed in many pieces, making it hard to see if cancer cells were at the edges.

For cancers not in a polyp, partial colectomy ─ surgery to remove the section of colon that has cancer and nearby lymph nodes ─ is the standard treatment. You typically won’t need any more treatment.

Treating stage II colon cancer

Stage II colon cancers have grown through the wall of the colon (called the muscularis propria), and may have even invaded into nearby tissue, but they have not spread to the lymph nodes.

Surgery to remove the section of the colon containing the cancer (partial colectomy) along with nearby lymph nodes may be the only treatment needed.

In certain cases, neoadjuvant therapy (therapy before surgery) may be recommended for stage II colon cancer, especially if the tumor has invaded or is attached to neighboring organs (T4b). This is generally considered for locally advanced colon cancer that is not initially operable. Decisions about what type of neoadjuvant therapy to give in these cases depends on whether the tumor has dMMR or MSI-H. If the tumor is dMMR or MSI-H, neoadjuvant immunotherapy (either PD-1 inhibitor alone or combination PD-1 and CTLA-4 inhibitor) is generally recommended. The type and duration of this therapy can vary as this approach remains very new. If the tumor is not dMMR or MSI-H, neoadjuvant chemotherapy is generally recommended.

If you did not receive neoadjuvant chemotherapy, after you recover from the colon surgery for treatment of Stage II cancer and if the tumor is found to not have dMMR or MSI-H, your doctor may recommend adjuvant chemo if your cancer has a higher risk of coming back (recurring) because of certain factors, such as:

• The cancer looks very abnormal (is high grade) when viewed closely in the lab.
• The cancer has grown through the colon wall (T4).
• The cancer has grown into nearby blood or lymph vessels.
• The surgeon did not remove at least 12 lymph nodes.
• Cancer was found in or near the margin (edge) of the removed tissue, meaning that some cancer may have been left behind.
• The cancer blocked (obstructed) the colon.
• The cancer caused a perforation (hole) in the wall of the colon.

If adjuvant chemo is given for high-risk stage II colon cancers, doctors generally recommend 5-FU or capecitabine. At times, oxaliplatin may also be offered. Each patient case is different and requires discussion about the risks and benefits of adjuvant chemo, as well as which type of chemo. Not all doctors agree on when chemo should be used for stage II colon cancers. It’s important for you to discuss the risks and benefits of chemo with your doctor, including how much it might reduce your risk of recurrence and what the likely side effects will be.

Treating stage III colon cancer

Stage III colon cancers have spread to nearby lymph nodes, but they have not yet spread to other parts of the body.

Surgery to remove the section of the colon with the cancer (partial colectomy), along with nearby lymph nodes, followed by adjuvant chemo is the standard treatment for this stage.

For chemo, either the FOLFOX (5-FU, leucovorin, and oxaliplatin) or CapeOx (capecitabine and oxaliplatin) regimens are used most often, but some patients may get 5-FU with leucovorin or capecitabine alone based on their age and health needs. In the past, most patients were recommended to received 6 months of adjuvant chemo for treatment of stage III colon cancer. Recent research has shown that 3 months of adjuvant chemo for some stage III colon cancers may be just as effective and is acceptable.

For some advanced colon cancers that cannot be removed completely by surgery (either tumor has invaded through the colon wall or presence of large bulky lymph nodes), neoadjuvant chemotherapy or neoadjuvant immunotherapy might be recommended to shrink the cancer so it can be removed later with surgery. Neoadjuvant chemotherapy is usually recommended if the tumor is pMMR or MSS. Neoadjuvant immunotherapy is usually recommended if the tumor is dMMR or MSI-H.

For some advanced cancers that have been removed by surgery but were found to be attached to a nearby organ or have positive margins (some of the cancer may have been left behind), adjuvant radiation therapy might be recommended. Radiation therapy and/or chemo may also be options for people who aren’t healthy enough for surgery or for when complete resection is not possible due to tumor location.

Treating stage IV colon cancer

Stage IV colon cancers have spread from the colon to distant organs and tissues. Colon cancer most often spreads to the liver, but it can also spread to other places like the lungs, brain, peritoneum (the lining of the abdominal cavity), or to distant lymph nodes.

In most cases, surgery is unlikely to cure these cancers. But if there are only a few small areas of cancer spread (metastases) in the liver or lungs and they can be removed along with the colon cancer, surgery may help you live longer. This would mean having surgery to remove the section of the colon containing the cancer along with nearby lymph nodes, plus surgery to remove the areas of cancer spread. In some cases, if the liver metastasis is not able to be surgically removed, ablation or embolization may be an option.

Chemo may begiven before and/or after surgery. If the metastases cannot be removed because they’re too big or there are too many of them, chemo may be given before surgery (neoadjuvant chemo). Then, if the tumors shrink, surgery may be tried to remove them. Chemo might be given again after surgery.

If the cancer has spread too much to try to cure it with surgery, chemo is the main treatment. Surgery might still be needed if the cancer is blocking the colon or is likely to do so. Sometimes, such surgery can be avoided by putting a stent (a hollow metal tube) into the colon during a colonoscopy to keep it open. Otherwise, operations such as a colectomy or a diverting colostomy (cutting the colon above the level of the cancer and attaching the end to an opening in the skin on the belly to allow waste out) may be used.

If you have stage IV cancer and your doctor recommends surgery, it’s very important to understand the goal of the surgery ─ whether it’s to try to cure the cancer or to prevent or relieve symptoms of the cancer.

Most people with stage IV cancer will get chemo and/or targeted therapies to control the cancer. Some of the most commonly used regimens include:

• FOLFOX: leucovorin, 5-FU, and oxaliplatin
• FOLFIRI: leucovorin, 5-FU, and irinotecan
• CAPEOX: capecitabine and oxaliplatin
• FOLFOXIRI: leucovorin, 5-FU, oxaliplatin, and irinotecan
• One of the above chemo combinations, plus either a drug that targets VEGF(bevacizumab, ziv-aflibercept or ramucirumab), or a drug that targets EGFR (cetuximab or panitumumab)
• 5-FU and leucovorin, with or without a targeted drug
• Capecitabine, with or without a targeted drug
• Irinotecan, with or without a targeted drug
• Cetuximab or Panitumumab
• Regorafenib, Trifluridine and tipiracil (Lonsurf), alone or in combination with Bevacizumab

The choice of regimens depends on several factors, including any previous treatments you’ve had and your overall health. If one of these regimens is no longer working, another may be tried.

For people whose cancer cells have changes in certain genes or proteins, targeted therapy drugs might be an option.

For people whose cancers cells have high levels of microsatellite instability (MSI) or changes in one of the MMR genes, an immunotherapy drug, such as pembrolizumab, nivolumab or Dostarlimab, may be an option.

For advanced cancers, radiation therapy can also be used to help prevent or relieve symptoms in the colon from the cancer such as pain. It might also be used to treat areas of spread such as in the lungs or bone. It may shrink tumors for a time, but it’s not likely to cure the cancer. If your doctor recommends radiation therapy, it’s important that you understand the goal of treatment.

Treating right-sided versus left-sided colon cancer

In recent years, research has shown that the genetic mutations found in colon cancer can be different depending on whether it started on the right or left side of the colon. These differences can affect how the cancer responds to certain treatments as well as a person’s prognosis (how well they do after treatment).

Right-sided colon cancer

The right-side of the colon includes the cecum, ascending colon, and about 2/3 of the transverse colon. Cancers that start on the right side of the colon are:

• Less common than left-sided colon cancer
• More likely to occur in older age
• More likely linked to a hereditary cancer syndrome
• More likely to be dMMR or MSI-H
• More likely to have a BRAF or KRAS mutation

These cancers tend to have a poorer prognosis if the cancer has advanced or spread outside the colon, compared to advanced cancers that started on the left. They are also unlikely to respond to anti-EGFR therapy, even if the tumor tests negative for RAS and BRAF mutations. Right-sided colon cancer may be more responsive to immunotherapy, compared to left-sided colon cancers.

Left-sided colon cancer

The left-side of the colon includes the rest of the colon, which includes the remaining 1/3 of the transverse colon, the descending colon, and the sigmoid colon. Cancers that start on the left side of the colon are:

• More common than right-sided colon cancer
• More likely to occur in younger age
• More likely to be diagnosed at an earlier stage due to symptoms
• More likely to have a HER2 mutation

These cancers tend to have a better prognosis if the cancer has advanced or spread outside the colon, compared to advanced cancers that started on the right. They are also more responsive to anti-EGFR therapy, if tests are negative for RAS and BRAF mutations. Left-sided colon cancers may be more responsive to chemotherapy, compared to right-sided colon cancers.

Treating recurrent colon cancer

Recurrent cancer means that the cancer has come back after treatment. The recurrence may be local (near the area of the initial tumor), or it may be in distant organs.

Local recurrence

If the cancer comes back locally, surgery (often followed by chemo) can sometimes help you live longer and may even cure you. If the cancer can’t be removed surgically, chemo might be tried first. If it shrinks the tumor enough, surgery might be an option. This might be followed by more chemo.

Distant recurrence

If the cancer comes back in a distant site, it’s most likely to appear in the liver first. Surgery might be an option for some people. If not, chemo may be tried to shrink the tumor(s), which may then be followed by surgery to remove them. Ablation or embolization techniques might also be an option to treat some liver tumors.

If the cancer has spread too much to be treated with surgery, chemotherapy ,targeted therapies, and/or immunotherapy may be used. Possible treatment schedules are the same as for stage IV disease.

Your options depend on which, if any, drugs you had before the cancer came back and how long ago you got them, as well as your overall health. You may still need surgery at some point to relieve or prevent blockage of the colon or other local problems. Radiation therapy may be an option to relieve symptoms as well.

Recurrent cancers can often be hard to treat, so you might also want to ask your doctor if clinical trials of newer treatments are available.

For more on recurrence, see Understanding Recurrence.