RAS/RAF mutation status in Algerian patients with metastatic colorectal cancer (mCRC) and impact of the primary site on clinical and prognostic outcomes

RAS/RAF mutation status is a major molecular outcome in colorectal cancer (CRC), and these mutations have been suggested as predictive and prognostic biomarkers. Previous reports have indicated differences in the biology and outcomes of colorectal cancer based on whether the cancer is right- or left-sided primary. Further division by right side, left side, and rectum, has also been studied. Potential differences in response to biologic agents were also noted based on the side of the primary lesion. the aim of this work is to try to find out impact of the primary site associated to RAS/RAF mutation status, on clinical and prognostic outcomes in patients with metastatic colorectal cancer (mCRC).

This is ambispective (retrospective + prospective) study conducted in oncology department of the military hospital of Oran, between January 1, 2020 and December 31,2022, to assess RAS/RAF testing practices and tumor characteristics in diagnosed patients with mCRC.

80 patients with adenocarcinoma histology were enrolled, the median age was 56 years [32-86] and a sex ratio was 1.5, stage IV disease (100%) and left-sided tumors (70,31%). Primary tumor site was sigmoid (46,88%), followed by descending (21,87 %), rectal (20%), coecum (18,75%) ascending (17.2%), and transverse (4.69%). Metastatic sites were liver 83,77%, lung 31,25 % and peritoneum 26,25%. RAS testing was performed in 71 (88,75%) patients, on primary tumor in 97,5%; RAS testing revealed that 42.25% of the tumors was mutated and 57.75% had wild-type (WT) sequences, mutation was more important on the right-sided primary 52% versus 40% on the left-sided one. The most common mutation was KRAS (83,33%), occurring largely in Exon2-Codon12 (84%); BRAF mutation was in just 2,5%. This resulted in addition of targeted therapy in 81,25% (49,75 % anti EGFR, 31,5 % anti VEGF) in WT mCRC, and significantly impacted treatment strategy of left-sided primary. Rapid progression (less than 6 months of treatment of the first line) was observed in 21.25% (rectum in 64.70%, followed by right-sided tumors 23.53% left colon in 11.77%) ,58.82% of this progression was observed in RAS muted tumors.

In our study, patients with right-sided primary cancer have more RAS mutations and more negative prognostic factors and indeed have inferior outcomes compared with those with a left-sided primary. Our work is still in progress and should provide further data on overall survival and progression-free survival.

The authors.

Has not received any funding.

All authors have declared no conflicts of interest.