Stage II Colon Cancer: To Treat or Not to Treat?

If you have been diagnosed with Stage II (two) colon cancer, you may be wondering if you need chemotherapy after surgery (called adjuvant chemotherapy). Studies have not found a clear answer to this question. Chemotherapy has side effects, so your provider will only want to give you chemotherapy if it is likely to help. Your provider will look at the risks and benefits of chemotherapy based on your health history, age, and other factors.

In stage I (one) colon cancer, surgery is the only treatment needed to remove the tumor. In stage III (three) colon cancer, when tumors have spread to the lymph nodes, you will have surgery followed by chemotherapy. Adjuvant chemotherapy lessens the risk of the cancer coming back (recurrence).  

Stage II disease falls somewhere in between. About 75% of people with stage II colon cancer will be cancer-free 5 years later without adjuvant chemotherapy. About 25% will still have cancer in their body at 5 years. Some of these patients may benefit from having chemotherapy after surgery. So, how do we know which patients are most likely to benefit from chemotherapy?

Staging

A tumor is staged using the "TNM" system:

T: Tumor size/depth.

N: If there are cancer cells in the lymph Nodes.

M: If there is Metastasis (if the cancer has spread to other parts of the body).

Stage II colon cancer includes tumors that are T3N0M0 or T4N0M0.

• T3 tumors grow through the muscularis propria (outer layer of the colon) and into the peri-colorectal tissues (tissue surrounding the colon).
• T4 tumors grow through the colon wall and attach to or invade a nearby structure or organ.
• N0 (N zero) means that no cancer cells were found in the lymph nodes.
• M0 (M zero) means that there is no metastasis.
• When looking at lymph node status, you also want to know the number of lymph nodes that were looked at by the pathologist (a doctor who looks at tumor cells under a microscope). This pathology report might state "fifteen benign lymph nodes (0/15)" or "tumor seen in sixteen of twenty lymph nodes (16/20)," meaning a total of 15 and 20 nodes were looked at, respectively.

You can learn more about colon cancer staging here.

Note: In the past, the Dukes' staging system was commonly used. Dukes B2 and B3 most closely correlate with Stage II in the TNM system. Currently, the Dukes system is no longer used in practice.

Not All Stage II Tumors Are Alike

Some stage II tumors may be more likely to come back after treatment (recur). These tumors have some features that raise the chance that the cancer will come back. These tumors may benefit from adjuvant chemotherapy.

Some of these high-risk features are:

• A T4 tumor – a tumor that has broken through the colon wall and into nearby tissues.
• If there is a bowel perforation (hole) or obstruction (blockage) at the time of diagnosis.
• Grade 3 tumors – these look very abnormal under the microscope. The grade is reported in the pathology report.
• Lymphovascular and perineural invasion –tumor cells are in the tiny blood vessels, lymph system, and nerves around the tumor. This will also be reported in the pathology report.
• Less than 12 lymph nodes were looked at by a pathologist.

If you have high-risk features, you should talk with your provider about chemotherapy options. There are some other factors that affect risk and play a role in whether or not to have chemotherapy. These include:

• Before surgery for colon cancer, a blood test for CEA (carcinoembryonic antigen) is done. CEA is a substance produced by the cancer cells, called a tumor marker. Elevated levels (CEA>5 ng/ml) before surgery may indicate a higher risk of recurrence. After surgery, CEA should return to a normal level. CEA is monitored in the months and years after treatment to look for recurrence, whether or not chemotherapy was received.
• Microsatellite Instability (MSI) status, which is classified as high (H) or low (L). Tumors with MSI-H status are thought to be less aggressive and may not benefit from adjuvant chemotherapy.

Genomic Profiling

Mutated (changed) genes that are a part of the tumor are looked at with genomic profiling tests. These are not the genes that you inherited from your parents. Genetics is the study of genes that are inherited and passed on from generation to generation. These genes are responsible for many things, including hair and eye color. Increased risk for certain diseases can also be passed on through genes and can be looked at using genomic profiling. The science used in genomic profiling is called genomics. This type of test looks at the genes that make up the tumor and evaluates how they interact and function. It looks at how active certain genes are within the tumor, which may affect how the tumor grows and responds to treatment. BRCA1 and BRCA2 ("breast cancer genes") are examples of these types of genes. Women with abnormal versions of these genes are at higher risk of developing breast cancer. Genomic profiling, using a gene signature, is an analysis of the level of expression of a group of genes in the tumor tissue, which is then used to predict outcomes.

A few companies have a panel of tumor genes that can help predict how likely the tumor is to recur after surgery. However, the tests have not been shown to be able to predict which tumors will benefit from chemotherapy. The tests can be expensive and may not be covered by insurance. Your provider can send information to your insurance company to ask for approval. These tests include:

• Oncotype DX Colon Cancer Recurrence Score – This test looks at 12 genes to predict the risk of recurrence. The sample is marked as low, intermediate, or high risk.
• ColoPrint – This test looks at 18 genes and marks the tumor as either high or low risk for recurrence.
• GeneFx – This test looks at 482 genes and marks the tumor as low or high risk.

Putting it All Together

There are a many things to think about when treating stage II colon cancer. Studies continue to look at the benefits and risks of treatment and which treatments are the best.

You and your providers should consider the stage and features of the tumor, your medical history, and your preferences about treatment. You play a role in this decision-making process and need to make a decision you can feel comfortable with, using all of the information available.