What Are Stage 2 and Stage 3 Colorectal Cancer?

The basics

Colorectal cancer involves the colon or rectum — both of which make up the large intestine, or bowel. It may be referred to as simply “colon cancer” or “rectal cancer” based on its exact location. 

Colorectal cancer is a leading cause of cancer in the U.S., affecting 1 in 23 men (4.3%) and 1 in 25 women (4.0%) in their lifetime. The most important factor that helps to predict survival is the stage at the time of diagnosis. 

The stage of colorectal cancer describes how big it is and how much it has spread. There are 5 stages of colon cancer (from 0 to 4). A higher stage means that the cancer is larger or has spread more. In the earliest stage (stage 0), the cancer is limited to the inner lining of the colon only. In the latest stage (stage 4), colon cancer has already spread to other areas of the body. 

Receiving a diagnosis of colorectal cancer is stressful for many reasons. You may be worried about side effects of treatment, how it will affect your daily life, and, most importantly, survival. When caught early, colon cancer is highly curable in more than 90% of cases. However, the outlook is not as favorable with more advanced stages. 

In this guide, we’ll discuss stage 2 and stage 3 colorectal cancer. We’ll also look at what these stages mean and the types of treatment used for each stage.

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Our Author:

Merin Kuruvilla, MD

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Dr. Merin Kuruvilla is a board-certified academic allergist/immunologist with an interest in clinical research. She has authored several peer-reviewed clinical research publications in leading medical journals.

What are the major differences between stage 2 and 3 colon cancer?

The major difference between stage 2 and stage 3 colorectal cancers is location: Stage 3 cancers have spread to nearby lymph nodes, whereas stage 2 cancers have not. But it might help to take a look at staging in a little more detail.

The stage of a cancer is determined using the TNM system, which incorporates the following: 

• Tumor (T): Extent of tumor growth into the wall of the colon

• Node (N): Number of lymph nodes affected by cancer

• Metastasis (M): Spread of cancer to other parts of the body

Each of these TNM elements is then further categorized with a number system. Because the lymph nodes are removed during surgery to be sampled for cancer, TNM staging occurs after surgery. 

Stage 2 colorectal cancer

Stage 2 cancers have spread outside the outer layers of the colon or into organs and tissues next to the colon. They do not involve surrounding lymph nodes. They may be either T3N0M0 or T4N0M0.

• T3 tumors have grown into the outer layers of the bowel wall but do not extend through it.

• T4 tumors have penetrated through all the layers of the colon. Cancer cells have spread outside the bowel wall and can even invade surrounding organs.

• N0 means that there is no spread to surrounding lymph nodes. 

• M0 means there is no spread to other organs.

Stage 3 colorectal cancer

Stage 3 cancers have spread to nearby lymph nodes but not anywhere else in the body. They may be any T, N1, M0, or any T, N2, M0.

• Any T: The tumor can be of any size.

• N1 tumors have spread to up to three nearby lymph nodes. 

• N2 tumors have spread to four or more nearby lymph nodes. 

• M0 means that no metastases are present (no spread to other organs).

How are stage 2 and 3 colon cancer diagnosed?

Colon cancer is usually found during colonoscopy. Once the biopsy confirms cancer, your provider will order more tests. These may include: 

• Lab tests, including blood counts and carcinoembryonic antigen (CEA) level 

• Imaging tests, such as computed tomography (CT) and positron emission tomography (PET) scan to look for tumor spread

Your treatment team will then come up with a treatment plan based on the results of these tests. Surgery is recommended to remove the tumor and all the surrounding lymph nodes at the same time. TNM staging to confirm stage 2 (no lymph nodes involved) or stage 3 disease (lymph nodes affected) can thus only be performed after surgical removal of the tumor and the lymph nodes.  

How does stage 2 colon cancer progress to stage 3?

The diagnosis of stage 2 colon cancer, as opposed to stage 3 colon cancer, has implications for treatment and expected survival. Overall, stage 2 disease is associated with significantly higher survival rates than stage 3 colon cancer. This is why additional therapies such as chemotherapy are advised after surgery for stage 3 colon cancer. Sometimes, even with careful surgery, the cancer can come back in people with stage 2 disease. 

How do you treat stage 2 and stage 3 colon cancer?

Surgery is the first and most important step in treating both stage 2 and stage 3 colorectal cancer. Surgery alone can cure early stage disease. Colectomy refers to removal of either all or part of the colon. In a partial colectomy, only part of the colon is removed. The entire colon is removed in a total colectomy. 

After removal of the cancer, the surgeon will reconnect the healthy colon if possible. If this is not possible, your surgeon will create an ostomy, which connects the remaining colon to the wall of the abdomen. This allows an alternate exit for your body waste. A colostomy may be temporary or permanent.

In addition to surgery, chemotherapy may be part of the treatment plan. Experts recommend additional, or “adjuvant,” chemotherapy for people who are at higher risk for the cancer returning. The likely reason that colon cancer returns after surgery is that some cancer cells survived or escaped the first round of treatment. Chemotherapy after surgery can get rid of the remaining cancer cells and increase the chances of a cure.

Adjuvant chemotherapy is administered after surgery to decrease the chances of the cancer coming back. Regimens that are commonly used in colon cancer are based on oxaliplatin and fluoropyrimidine medications. These regimens commonly include: 

• 5-Fluorouracil (5-FU) or capecitabine

• Oxaliplatin

Examples of these regimens include:

• Capecitabine (taken by mouth)

• 5FU + folinic acid (leucovorin) administered by IV infusion

• FOLFOX: 5-FU + oxaliplatin + folinic acid (leucovorin), all administered by IV infusion

• CAPOX: oxaliplatin (given intravenously) + capecitabine (taken by mouth) 

A common side effect of adjuvant chemotherapy is nerve damage from oxaliplatin. This can cause permanent numbness and tingling as well as pain in the hands and feet. These symptoms may persist even after treatment is completed. The risk of nerve damage is related to the dose and duration of oxaliplatin therapy.

How do treatment options differ between stage 2 and 3 colon cancer?

The main difference in the treatment of stage 2 versus stage 3 colon cancer is the need for adjuvant, or postoperative, chemotherapy. The benefits of adjuvant chemotherapy have been clearly proven for stage 3 disease (more below). On the other hand, the role of chemotherapy for stage 2 cancer is still controversial.

The decision to prescribe chemotherapy is often not an easy one. Even though chemotherapy for colorectal cancer is helpful at preventing a relapse and is less toxic than treatments for other cancers, it still has a lot of side effects. This is why people who do receive chemotherapy need to be carefully selected. Surgery alone can cure the majority of people with early stage colon cancer. If everyone with colon cancer was to get chemotherapy, this would expose a lot of people to unnecessary toxic side effects.

Stage 2 colon cancer

Deciding upon the best way to treat stage 2 disease is one of the most challenging parts of managing colorectal cancer. There are many questions that remain about the best and safest way to achieve a cure. This is because, as compared with other stages, stage 2 cancers vary highly in terms of their risk for recurrence. 

In 20% to 25% of cases, the cancer returns within 5 years. Some of these cases may benefit from receiving chemotherapy after surgery. But how do your providers decide who is most likely to need additional chemotherapy? 

Chemotherapy is recommended when there is a high risk for recurrence. These high risk characteristics include:

• T4 stage

• Bowel obstruction by tumor

• Bowel perforation 

• Less than 12 lymph nodes removed for testing at the time of surgery

• Invasion of the tumor into nerves or vessels

• Certain characteristics of cancer cells under the microscope

High-frequency microsatellite instability (MSI-H) status is another predictive test used to select people for adjuvant chemotherapy. MSI is caused by genetic mutations. People with MSI-H tumors have a lower risk of relapse and do not need adjuvant chemotherapy, even if they have other high-risk characteristics. 

The decision to prescribe chemotherapy to someone with stage 2 colon cancer must therefore be made on a case-by-case basis. The risks and benefits of therapy should be considered.

Stage 3 colon cancer 

People with stage 3 disease (lymph node involvement) routinely receive adjuvant chemotherapy. This is because with surgery alone, less than half the people with stage 3 disease will be free of cancer 5 years later. Adjuvant chemotherapy can reduce this risk of recurrence by 30% to 50%, and it improves overall survival by 30%.

A 3- or 6-month course of FOLFOX or CAPOX may be used to treat stage 3 colon cancer after surgery. In one comparison of 3 versus 6 months of adjuvant chemotherapy, 3 months of chemotherapy did not offer the same disease-free survival as 6 months of chemotherapy overall. But a 3-month course of chemotherapy was just as effective in people with lower risk for recurrence. A shorter course of chemotherapy could lessen treatment-related side effects and may be appropriate for many people.  

In people with stage 2 or 3 rectal cancer, chemotherapy and radiation are used to shrink the tumor before surgery. This is called neoadjuvant therapy. It helps the surgeon remove the tumor more easily and reconnect the bowel if possible. An additional benefit of neoadjuvant therapy is that it may help to kill hidden and undetected cancer cells even earlier.  

Postoperative radiation therapy may also be recommended in rare instances. But preoperative (neoadjuvant) radiation is preferred.  

Keep in mind

Current guidelines recommend adjuvant chemotherapy for patients with stage 3 colon cancer, regardless of age. And even though adjuvant chemotherapy is currently used for high-risk stage 2 colon cancer, there is limited evidence to support this guidance. Future studies are needed to establish its value in this scenario. 

Also, further studies are needed to answer several other questions. These include the optimal duration of adjuvant chemotherapy and the role of neoadjuvant therapy. This would help to tailor treatment for individual people with colon cancer. 

The good news is, the ability to answer these questions may be on the horizon. For instance, clinicians are now able to test for tumor DNA in blood samples. This can help detect residual disease (cancer that may be left over after surgery and/or chemotherapy). Should this testing become routine, it would be a powerful tool in the goal of targeting treatment plans to individual patients.

Why trust our experts?

Written by:

Merin Kuruvilla, MD

Merin Kuruvilla, MD, is a board-certified allergist/immunologist at Emory University in Atlanta. She has authored several peer-reviewed publications in the field.

Edited by:

Mandy Armitage, MD

Mandy Armitage, MD, has combined her interests in clinical medicine with her passion for education and content development for many years. She served as medical director for the health technology companies HealthLoop (now Get Well) and Doximity.

Reviewed by:

John Strickler, MD

John Strickler, MD, joined the Duke University faculty in 2011 and is now an associate professor of medicine in the division of medical oncology. His research focuses on precision cancer medicine: identification of genomic biomarkers that predict sensitivity or resistance to targeted therapies and immunotherapy.

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