What is tumor location or tumor sidedness?

Tumor location refers to the site of the primary tumor (tumour) of your colorectal cancer.  

The large intestine (bowel) is made up of 6 segments, cecum (caecum), ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. The hepatic flexure (right colic flexure) is the turning point between the ascending colon and transverse colon. The splenic flexure (left colic flexure) is the turning point between the transverse colon and descending colon. Colorectal cancer (bowel cancer) can develop in any of these locations.

Often, colorectal cancer is referred to as “right sided” or “left sided”. This is the “sidedness” of the tumor. Right-sided tumors, also known as proximal tumors, are located in the cecum, ascending colon, hepatic flexure, or the transverse colon. Left-sided tumors, also called distal tumors, are located in the splenic flexure, descending colon, sigmoid colon, or rectum.

Tumor location is both a prognostic factor and a predictive biomarker. Tumor sidedness gives information about the likely course of the disease (prognosis), and tumor location is a predictor of which treatments may be more or less effective for a particular colorectal cancer.  

Why are right sided colon cancers and left sided colon and rectal cancers different?

Several factors likely contribute to the differences in right-sided colon cancers and left-sided colorectal cancers.

• The right and left sides of the colon develop from two different parts of the embryo, the midgut and the hindgut.
• As digested food travels through the large intestine, the right and left sides are exposed to different nutrients and digestive substances, such as bile acids.
• The populations of normal gut bacteria (intestinal microbiome) that live in the large intestine vary between the right side of the colon and the left side of the colon and rectum.

‍How are right-sided colon cancer and left-sided colorectal cancer different?

Right-sided colon cancer has a better prognosis in early stages (stage I and stage II). Left-sided colon cancer has a better prognosis at advanced stages (stage III and stage IV / metastatic colorectal cancer).

Right-sided colon cancers and left-sided colorectal cancers may also have differences in their tumor shape and in their subtype of adenocarcinoma. Right-sided tumors tend to be flat shaped and are more likely to be part of the mucinous subgroup of adenocarcinomas. Left-sided tumors tend to be polyp shaped and are more likely to be tubular or villous adenocarcinomas.

‍How is tumor location or tumor sidedness determined?

The location of your colorectal cancer (CRC) may be identified in several ways. It may be described in imaging reports like CT scan, PET scan, or MRI scan. It can be noted in reports from surgical procedures like colonoscopy and colectomy (colon resection), or in pathology reports that describe the histology (microscopic characteristics) of your colorectal carcinoma.

How is tumor location or tumor sidedness reported?

Tumor location may be reported as “right-sided” or “left-sided”, or as “proximal” or “distal”. The specific location of your colorectal tumor will also be noted, such as splenic flexure, sigmoid colon, or rectum.  

How do my tumor location or tumor sidedness results impact my treatment?

If your colorectal cancer is right-sided, also known as proximal, (located in the cecum, ascending colon, hepatic flexure, or transverse colon)

• Immunotherapy with immune checkpoint inhibitors, such as pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy), is often effective against right-sided colorectal cancer.
• Immune checkpoint inhibitors use your own immune system to kill cancer cells by promoting stronger responses against cancer cells from white blood cells in your tumor (tumor-infiltrating lymphocytes).
• Bevacizumab added to conventional chemotherapy is more effective than EGFR inhibitors combined with conventional chemotherapy in right-sided cancers.

If your colorectal tumor is left-sided, also known as distal, (located in the splenic flexure, descending colon, sigmoid colon, or rectum)

• Adjuvant chemotherapy with fluorouracil based regimens (FOLFOX, FOLFIRI) is effective against left-sided colorectal cancer. Adjuvant therapy is a secondary treatment given after the primary treatment to prevent recurrence of the cancer. Usually this is drug therapy that treats cancer cells that may remain in the body after surgery.
• Conventional chemotherapy combined with cetuximab (EGFR inhibitor) targeted therapy is more effective than chemotherapy combined with bevacizumab in left-sided cancers.

Additional targeted therapy treatment options may be indicated based on the results of other biomarker testing such as microsatellite stability (MSS) and microsatellite instability (MSI), RAS gene mutation status (KRAS or NRAS), BRAF mutation status, and HER2 amplification or overexpression status. Talk to your oncology healthcare team about further biomarker testing, and how your results can impact your treatment.

‍Who should be tested for tumor location / tumor sidedness?

Tumor location should be determined for all colorectal cancer patients at the time of diagnosis.