Abstract
Clinico-pathological differences between adenocarcinoma in the right and left colo-rectum play a role in determining the prognosis and response to treatment. Studies suggest that primary tumor location is more relevant as the disease progresses and reflects a possible difference in biology and response to therapy. This review aims to explore the clinico-pathological features of right and left colo-rectum and the impact of primary tumor location on prognosis of CRC as well as discuss the available clinical data on tumor sidedness in metastatic colorectal cancer. In so far as the clinical data of tumor sidedness is concerned, very few reviews have discussed the clinical implications of sidedness in heavily pre-treated metastatic colorectal cancer (second and subsequent lines of therapy in metastatic disease). This review aims to fill the current gap in this setting.
Highlights
Colorectal cancer (CRC) is the third most common cancer globally, with an estimated 1.8 million new cases and 881,000 deaths occurring in 2018 [1]
Whereas the authors acknowledge that the existing tumor sidedness data is convincing, the planning, and conduct of clinical trials with inclusion of prospective tumor sidedness will only boost the validity of historical data
Retrospective analysis of multiple randomized phase II/III clinical trials points to the effectiveness of anti-EGFR therapy in Left sided RAS wild-type metastatic colorectal cancer (mCRC) whereas the same have reported a lack of benefit in right sided tumors
Summary
Colorectal cancer (CRC) is the third most common cancer globally, with an estimated 1.8 million new cases and 881,000 deaths occurring in 2018 [1]. Primary tumor location based retrospective analysis of this trial showed significantly prolonged median overall survival (OS) in patients with left sided tumors as compared to right sided tumors, irrespective of allocation to Cetuximab or Bevacizumab group. In 2017, Arnold et al [20] published the results of a retrospective pooled analysis from six randomized trials of tumor sidedness and anti-EGFR therapy in patients with RAS wild type (KRAS/NRAS wild type) metastatic colorectal cancer. Holch et al [21] performed a meta-analysis of 13 firstline randomized controlled trials and one prospective pharmacogenetic study in metastatic mCRC In this analysis; all first line anti-EGFR vs anti-VEGF studies in RAS wild type mCRC patients revealed a significant OS benefit of anti-EGFR therapy in left sided tumors (HR = 0.71, p = 0.0003). The PFS benefit with Panitumumab plus FU plus Leucovorin during maintenance treatment was independent of tumor sidedness [22]
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