Primary site and treatment impact in unresectable metastatic colorectal cancer

ABSTRACTIntroduction Colorectal cancer is a heterogenous disease, with various clinical and molecular subtypes related to the primary site (left versus right colon) of the original tumor. Primary colon tumor side is both a prognostic and predictive marker in metastatic colorectal cancer.Areas covered There is an increasing body of evidence for how primary site may impact treatment decisions in metastatic colorectal cancer. We reviewed the evidence for its prognostic and predictive value.Expert opinion Primary site is a prognostic marker in metastatic colorectal cancer, with right colon tumors being associated with more aggressive disease behavior and poorer outcomes. Primary site also appears to predict for outcomes to various treatments, in particular anti-EGFR antibodies. As our understanding and testing of the molecular and biological differences within colorectal cancer increases beyond primary site, this should be integrated into the current treatment algorithm to ensure an individualized patient-centered approach to care.KEYWORDS: Anti-EGFR antibodycolorectal cancermolecular subtypeprimary sidepredictive factorsprognostic factorstreatment Article highlights Primary site is a prognostic factor, with right colon tumors being associated with worse outcomes compared to cancers with a primary left colon tumor.Primary site appears to be a predictive marker for treatment effect from anti-EGFR antibodies, with a significant survival benefit seen in those with left colon tumors only. Until the results of the recent phase III randomized PARADIGM study, this was based on retrospective data and a meta-analysis of subgroups of clinical trials only.Various clinical and molecular factors impact treatment choice in metastatic colorectal cancer, and further molecular characterization of tumors in the future beyond primary site may lead to a more individualized approach to patient care.Declaration of interestT Price has affiliations with Amgen and Merck, and has served on the advisory board for Merck Sharpe & Dohme ad board. T Price is also an Editorial Board member of Expert Review of Anticancer Therapy.The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Additional informationFundingThis paper was not funded.