In Stage 4 Colon Cancer, Does Right- or Left-Sided Tumor Location Matter?

We divide colon cancer by location into right-sided and left-sided disease. During embryonic development in the womb, the intestine develops from two different sections that join. The superior mesenteric artery supplying the bowel determines the right/left distinction.

Studies show genetic alterations, particularly BRAF mutations, are more common in right-sided colon cancer. In Lynch syndrome, most tumors are in the right colon, and right-sided cancers are also more common in women. They resemble small-intestinal cancers. Left-sided colon cancers are more common in men; their tumors more often show chromosomal instability, with KRAS and p53 mutations prominent.

What Does This Right–Left Difference Mean for Treatment and Disease Course?

Stage 4 colon cancer treatment includes new-generation drugs called biological agents in addition to chemotherapy. Many studies investigate bevacizumab (Altuzan), cetuximab (Erbitux) and panitumumab (Vectibix), seeking to identify which patients benefit most from these targeted drugs.

Not all cancer cells are alike. They differ by genetic alterations, which also determine the types of cancer treatment used.

RAS Mutation

First discovered in a mouse sarcoma caused by viral infection and named after it (rat sarcoma), RAS protein has three types: KRAS, NRAS and HRAS. Bound to the inner cell membrane, it becomes activated by external stimuli and sends intracellular signals promoting division. Among these, a mutation in KRAS occurs in many cancer types.

This genetic mutation occurs in % 40 of metastatic colon cancers. Those with it are called RAS-mutant and those without it RAS-wild. Certain targeted drugs (biological agents) seem less effective in RAS-mutant colon cancer. All patients with metastatic colorectal cancer should therefore be tested for this alteration to select the targeted smart drugs used in the fourth stage.

The Study

Preliminary CALGB results showed that in RAS-wild tumors located in the left colon, overall survival with cetuximab was 10 months longer than with bevacizumab. For right-sided tumors, the opposite applied: overall survival was 5 months longer with bevacizumab.

These findings suggest anti-EGFR drugs (cetuximab, panitumumab) work better in left-sided cancer and bevacizumab in right-sided cancer. However, one study alone is insufficient to change practice. Right- and left-sided tumors have different characteristics; in stage 4 disease, mutation status must be determined, and larger future studies are awaited for drug-selection developments affecting treatment decisions.