Right vs Left Colorectal Cancer
Colorectal Cancer (CRC) is the third most common cancer worldwide with a high mortality rate at the advanced stages. Around 1 in 20 people develop colorectal cancer and 90% of diagnosed cases are in people who are over the age of 60 in the UK. However, the treatment of colorectal cancer is heavily reliant on the anatomical position of the tumour within the bowel. This is due to CRC not being a single type of tumour cell; its pathogenesis depends on the anatomical location of the tumour and differs between right side and left side of the colon. Tumours in the proximal colon (right side) and distal colon (left side) exhibit different molecular characteristics and histology. As a result, CRC has been divided into right sided colon cancer (RSCC) and left sided colorectal cancer (LSCC). The definition of RSCC is cancer of the cecum and the ascending colon up to the hepatic flexure. While the left side is defined as cancer of the splenic flexure and in regions distal to the splenic flexure, including the rectum. Embryologically, the right side of the colon arises from the midgut while the left side arises from the hindgut. As a result, there are known genetic predisposition of CRC, especially in RSCC, where BRAF mutations are more commonly observed.
After the landmark CALGB/SWOG 80405 study, it was found that overall survival was 14 months better for patients with left-sided tumours, vs right-sided ones. Therefore, right sided colon cancer is associated with poorer prognosis when compared to left sided colon cancer. There are many explanations for this, one being BRAF mutation being more commonly observed in RSCC, which is associated with aggressive CRC hence poor prognosis. Another reason for RSCC exhibiting a poorer response may be due to diagnosis being made much later than LSCC. This observation reflects the tendency for right-sided CRC to produce symptoms only at later and more advance stages of the cancer.
Right-sided colon cancers tend to be diagnosed much later than left-sided colon cancers. This clinical observation reflects the tendency for right-sided colon cancers to produce symptoms only when they are relatively advanced. Stool is liquid on the right side of the colon, and the cecum is a large and wide structure, so the bowel symptoms that typically herald the presence of colon cancer—such as pain, cramps, or blockage—do not occur until an extensive mass has formed, sometimes over many years.
Treatment of CRC is normally reliant on early diagnosis through endoscopy and curative surgery can be performed to remove polyps. Chemotherapy and radiotherapy also play a significant role in pre/post operation to maximise the success of the surgery. Although, in later stages of RSCC and LSCC, systemic treatment relies solely on targeted therapy, chemotherapy and immunotherapy. However, immune checkpoint inhibitors have shown little success in treating CRC, hence targeted agents in combination with chemotherapeutics remain the gold standard. Interestingly, EGFR antibodies appear to work better in LSCC whereas RSCC are more responsive to VEGFR antibodies. These targeted agents will augment the chemotherapy regimens such as FOLFOX (folinic acid, fluorouracil & oxaliplatin) and FOLFIRNOX (folinic acid, fluorouracil, oxaliplatin & irinotecan) in treating CRC. Current research of CRC is focusing on optimising diagnostic time for curative treatment and continual research into the cancer biology will provide a better idea into what signalling pathway can be targeted in treatment of CRC.
Sources
https://www.hematologyandoncology.net/archives/january-2017/right-sided-vs-left-sided-colorectal-cancer/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089587/
