Practical Implications of KRAS Mutation Status and Sidedness of Primary Tumour in Patients with Colorectal Cancer and Synchronous Liver Metastases: A Subset Analysis of the CoSMIC Study.

Abstract

Simple SummaryPatients presenting with liver metastases at the time of diagnosis of their colorectal cancer (termed ‘synchronous disease’) have a worse outcome than those whose disease is limited to the primary bowel tumour. There is evidence to show that patients with tumours on the right side of the colon have worse survival. Furthermore, mutations in the KRAS gene have also been shown to adversely affect outcome. This study explores the association between the side of the primary colorectal tumour in patients with synchronous disease and mutations in the KRAS gene on survival. We analyse a specific cohort of patients from the previously published CoSMIC study who presented with colorectal cancer and synchronous liver metastases and who had their colorectal tumour analysed for KRAS mutations. We find that for this cohort, neither mutations in the KRAS gene nor the side of the colon tumour influenced survival.Patients with colorectal cancer presenting with synchronous liver metastases have less favourable outcomes than those with primary-only disease. There is evidence of different genetic mutational signatures according to the sidedness of the primary tumour. KRAS mutations are key driver mutations in colorectal cancer progression. This post hoc analysis of the previously reported CoSMIC inception cohort explores the association between primary tumour sidedness and KRAS mutational status on the outcome of patients with colorectal cancer and synchronous liver metastases. Patients diagnosed with synchronous disease were recruited between April 2014 and March 2017 and, after exclusions, 83 patients undergoing colorectal primary KRAS mutation testing constituted the final study population. Data were collected prospectively on demographic profiles, treatment, and outcomes. Twenty-one patients (25%) had right-sided tumours and 62 (75%) had left-sided tumours, with 46 (55%) and 37 (45%) exhibiting wildtype and mutated KRAS, respectively. There was no difference in distribution of liver metastases by KRAS status (unilobar vs. bi-lobar; p = 0.58; Fisher’s Exact test) and no difference in 5-year survival according to KRAS mutation status (Log-rank test, p = 0.82) or tumour sidedness (p = 0.16). In summary, in this cohort of patients with colorectal cancer and synchronous liver metastases, neither KRAS mutation status nor tumour sidedness influenced survival.