Opinion statement
Colorectal cancer does not represent a single anatomic entity and side of origin has a key impact on prognosis and response to different systemic therapies. Compared to tumours arising in left colon, right colorectal cancers rely on the activation of different molecular pathways (e.g. BRAF mutation and MSI status). From a clinical point of view, this results in a different response to anti-EGFR agents. Current guidelines suggest the use of cetuximab or panitumumab in RAS wild-type disease and left colon cancer especially for cytoreduction/conversion purposes, since the expected benefit in right colon cancer is absent or clinically modest. The prognostic role of microbiota in colorectal cancer disease deserves more clarification before being considered in common clinical practice. Screening policies could also be affected by these new acquisitions. At the moment, sidedness should be considered as a strong prognostic variable and a surrogate predictor of different activity of anti-EGFR agents in the metastatic setting. Its role in early stages of resected disease is still uncertain.
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