Sidedness Biomarker

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What is tumor sidedness and how is it a biomarker?

The colon has two sides: the right side and the left side. On the right side is the cecum and the ascending colon, and on the left side is the descending colon, sigmoid colon, and the rectum. The right and left sides of the colon are connected by the transverse colon. Colorectal cancer can develop in any of these locations.  

Depending upon its location, colorectal tumors are often referred to as “left-sided” or “right-sided.” This classification is referred to as the “sidedness” of the tumor.  

Research suggests that there are biological differences between left-sided and right-sided CRC tumors that affect tumor progression, and these differences are what make tumor sidedness a biomarker.  

Why are there biological differences between the left and right colon? There are several factors that likely contribute to these differences,

• The two halves of the colon develop from different tissues in babies prior to their birth.
• The chemicals in contact with the wall of the colon differ as food is digested and processed.
• The community of bacteria present in the two parts of the colon, known as the microbiome, differ.

When and how is tumor sidedness determined?

Tumor sidedness is determined at diagnosis. Your tumor location may be described in imaging reports, surgical reports, or pathology reports.

If you are unsure of your tumor location, it is best to ask your medical care provider for this information.

What is the difference between right-sided and left-sided tumors?

The most obvious difference between right-sided and left-sided tumors is their location. However, there are many other differences between right-sided and left-sided tumors that may affect patient care.   

Right-sided colon cancers make up 15 to 20% of all colorectal cancers, with most right-sided tumors occurring in the ascending colon. These tumors are often associated with the following: 

• More often diagnosed in women and in older patients
• Symptoms are more likely to include anemia, vomiting, and unintentional weight loss  
• More likely to be MSI-H/dMMR that means these tumors have a defective repair mechanism for errors that occur as cells divide that can have important treatment implications.  
• Patients with Lynch syndrome are more likely to have right-sided tumors 
• More likely to have KRAS and BRAF mutations that can drive the tumors to grow and that have important treatment implications 
• Tend to be sessile (flat) so that it is harder for them to be seen on colonoscopy  
• Because of their location and shape, these tumors are often diagnosed at later stages 
• More likely to metastasize (spread) to the peritoneum (the lining of the abdominal cavity) than the liver or lung. 

Left-sided colorectal cancers make up most of all colorectal cancers, with the majority (up to 50%) occurring in the sigmoid colon. These tumors are often associated with the following:

• More often diagnosed in men and in younger patients
• Often result in “classical” colorectal cancer symptoms, including changes in bowel habits, blood in the stool, and bowel obstructions 
• More likely to have HER2 amplification which is a genetic change in the tumor tissue that has important treatment implications 
• Due to their location and associated symptoms, these tumors are often diagnosed at earlier stages 
• More likely to metastasize to the lungs or liver than the peritoneum.

What does my tumor location mean for me?

If you have right-sided colon cancer, your tumor originated in the right side of your colon. 

• Surgery for right-sided tumors may result in the removal of the cecum, ascending colon, and/or a portion of the transverse colon. You may experience looser and more frequent stools following surgery. Often the bowel symptoms moderate over time as the body adjusts to the shorter colon that is left after surgery.
• Right-sided tumors generally respond better to immunotherapies (pembrolizumab, nivolumab, and ipilimumab) than left-sided tumors. 
• Combination of anti-VEGF therapy (bevacizumab) and conventional chemotherapy may be more effective than anti-EGFR therapies (cetuximab and panitumumab) combined with conventional chemotherapy in right-sided cancers.  
• The status of other biomarkers may be used to guide treatment decisions. 

If you have left-sided colorectal cancer, your tumor originated in the left side of your colon.

• Surgery for left-sided tumors may result in the removal of the descending colon, sigmoid colon, and/or a portion of the transverse colon.
• Adjuvant conventional chemotherapies, such as FOLFOXIRI, FOLFOX or FOLFIRI, are often more effective against left-sided colorectal cancers.  
• Combination of anti-EGFR therapies (cetuximab and panitumumab) and conventional chemotherapy may be more effective than anti-VEGF therapy (bevacizumab) combined with conventional chemotherapy in left-sided cancers.  
• The status of other biomarkers may be used to guide treatment decisions and use of targeted therapies. 

The most effective treatment varies by individual. It is best to speak with your medical team to learn more about the best treatment options for you and whether you may benefit from additional biomarker testing. 

Resources 

• Sidedness: What side is your cancer on?
• CRC Tumor Sidedness Plays an Increasing Role in Clinical Practice